MedWorm provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest medical blog items that have been tagged with 'cancer markers'. Sat, 03 Sep 2011 02:52:20 +0100 http://www.medworm.com/index.php?rid=5159878&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F08%2Fwclc-2011-oral-presentations-more-genomics.html This study showed the potential for using DNA methylation profiles in targeted therapy profiles.  This seemed like a lot of fancy razzle-dazzle in this context and I'm unclear what it would really add in a practical sense; it seems to me most of the work on DNA methylation patterns in lung cancer has been focused on identifying markers for early diagnosis in serum. (Source: The Daily Sign-Out) The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=5159878 Tue, 23 Aug 2011 20:12:54 +0100 5159878 http://www.medworm.com/index.php?rid=5125976&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F08%2Fwclc-2011-oral-presentations-squamous-cell-carcinoma.html This study involved a tissue microarray constructed from 568 patients with stage 1 NSCLC with detailed histopathological and clinical data.  SOX2 gene data was determined by FISH and SOX2 protein expression was assessed by IHC.  This data was correlated then with clinicopathological findings and OS and cancer-specific survival. Increased SOX2 gene amplification or polysomy was found in 4% of (17/429) evaluable samples but 16/17 (94%) were associated with non-ADC histology.  SOX2 protein expression was found in 48% of NSCLC and was associated with non-ADC histology (P<0.001): SOX2 expression was identified in 78% of SQC specimens (178/227) but only in 15% of ADC (29/191).  Further, SOX2 protein expression was significantly associated with high grade tumors, patien... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=5125976 Fri, 12 Aug 2011 12:05:00 +0100 5125976 http://www.medworm.com/index.php?rid=5119014&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F08%2Fwclc-2011-oral-presentations-genomics.html This study provides some preliminary benchmarking data to discuss with clinicians, although I would provide a caveat that there is likely to be a referral bias (since this is a single-institutional study from one of the world’s most reknown cancer centers) that overestimates the frequency of driver mutations in ADC. Finally, O016.06 is another presentation from the MSKCC that examined the prognostic impact of driver mutations in lung ADC with respect to smoking history.  There is important background that puts this study in context, namely, the demonstration of an independent dose-dependent relationship between smoking history and survival in patients with advanced stage NSCLC with never-smokers living 50% longer than smokers (Janjigian et al., Cancer 2010).  The authors revi... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=5119014 Wed, 10 Aug 2011 12:09:27 +0100 5119014 http://www.medworm.com/index.php?rid=5086570&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F08%2Fwclc-2011-oral-presentations-tumor-microenvironment.html This study highlights the importance of localization of immune cell response but also underscores the challenge for future studies to use more refined quantitative assessments of immune cell subpopulations and relative expression of IHC staining intesity (such as utilizing digital imaging and image analysis).  MO 22.04, also from session VIII, presented interesting complementary data to the above presentation. This study examined 196 resected stage 1-3A NSCLC using IHC for infiltrating CD8+ and FOXP3+ cells.  They counted cells expressing these markers in tumor and stromal regions in five "randomly selected" high-power-fields and reported their data as the number of cells per mm2 for each region.  They used median cell count as the cutoff to define patient subgr... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=5086570 Tue, 02 Aug 2011 10:01:00 +0100 5086570 http://www.medworm.com/index.php?rid=5069835&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F07%2Falk-positive-lung-adenocarcinoma-nejm-case-records.html The July 14, 2011 issue of The New England Journal of Medicine features a nice case report as part of the weekly "Case Records of the MGH" series.  I thought those interested in lung cancer would benefit from reading this, especially in light of recent advances recognizing ALK translocations as driver mutations in about 5% of lung ADC--and the drug crizotinib to treat these particular tumors (my previous post on ALK inhibition in lung cancer). (Source: The Daily Sign-Out) The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=5069835 Wed, 27 Jul 2011 14:04:46 +0100 5069835 http://www.medworm.com/index.php?rid=4795068&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F05%2Fddr2-kinase-mutations-in-lung-squamous-cell-carcinoma.html Yes--you read that right! The journal Cancer Discovery reports in a publish ahead-of-print article (abstract)the discovery of mutations in the discoidin domain receptor 2 tyrosine kinase (DDR2) gene in a series of lung squamous cell carcinomas (SQC) that may identify a  potential therapeutic target similar to those described for lung adenocarcinomas.  Interestingly, DDR2 is a receptor kinase that normally binds collagen as its ligand and has been shown to promote cell migration, proliferation, and survival when activated by ligand binding and phosphorylation. While subtypes of lung adenocarcinoma (ADC) have been increasingly better defined and characterized on multiple levels with respect to identifying therapeutic targets/responses, minimal progress has been made with squamous... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4795068 Fri, 06 May 2011 16:40:35 +0100 4795068 http://www.medworm.com/index.php?rid=4734689&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F04%2Fascocap-clarifications-to-erprher2-testing-guidelines.html ASCO is publishing a clinical notice regarding clarifications to previously published guidelines for HER2 testing and estrogen receptor (ER) and progesterone receptor (PR) testing in breast cancer.  A summary can be found at the CAP Web site. The clarifications were needed since these tests are generally run on the same specimen in routine practice and reconcile discrepancies between the two guidelines regarding cold ischemia time, handling of remotely obtained specimens, appropriate fixation times in NBF, and selection of optimal areas for testing. This is a welcomed development for us practicing grunts (who must acknowledge, explain and document this stuff) but shouldn't affect current routine practice or patient testing. (Source: The Daily Sign-Out) The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4734689 Wed, 20 Apr 2011 19:43:39 +0100 4734689 http://www.medworm.com/index.php?rid=4684777&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2011%2F04%2Faberrant-wnt1-and-beta-catenin-expression-in-nsclc.html This month's April 2011 Journal of Thoracic Oncology has an interesting paper by Xu and colleagues (abstract) that examines Wnt1 expression in non-small cell lung cancer (NSCLC) in relation to downstream Wnt signaling molecules, including beta-catenin, and correlates different marker expression with traditional clinicopathological parameters. This is an immunohistochemical study of a tissue microarray composed of 262 NSCLC resected specimens.    The authors define aberrant beta-catenin expression as: 1) decreased membranous pattern in less than 70% of tumor cells, 2) cytoplasmic pattern of expression, or 3) nuclear pattern of expression.  As expected, the majority of patients are stage 1 or 2 but nearly 36% of the study population are never-smokers--over 50% in ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4684777 Tue, 05 Apr 2011 19:55:50 +0100 4684777 http://www.medworm.com/index.php?rid=4275599&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F12%2Foptimal-panel-for-differentiating-nsclc-in-small-specimens.html This study makes several practical points that can be nicely summarized as bullets: For ADC the most sensitive marker and best negative predictor is CK7: 93% sensitivity, 91% NPV. For ADC the most specific marker and best positive predictor is Napsin A: 94% specificity, 90% PPV. TTF-1 has similar specificity as Napsin A for ADC. For SQC the most sensitive marker and best negative predictor is p63: 84% sensitivity, 86% NPV. For SQC the most spepcific marker and best positive predictor is NTKR2 (a neurotrophic tyrosine kinase receptor, rarely used outside of research labs) but CK5/6 has a nearly identical specificity and PPV: about 95% specificity, about 95% PPV. No single marker is BOTH highly sensitive and specific for either ADC or SQC. The authors identified a 6-marker panel that inclu... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4275599 Tue, 21 Dec 2010 12:22:00 +0100 4275599 http://www.medworm.com/index.php?rid=4125295&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F11%2Fdetecting-alk-in-endobronchial.html The October 15, 2010 issue of Clinical Cancer Research has an intriguing article that could have major implications for staging and prognostication in lung cancer.  Sakairi and colleagues from Chiba Cancer Center in Japan show the feasibility of using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to obtain specimens suitable for testing for EML4-ALK fusion gene in NSCLC lung cancer patients with proven hilar and/or mediastinal lymph node metastasis. The protocol for this study involved chest CT followed by EBUS-TBNA for lymph nodes >5 mm.  They obtained a histologic core using a 22-gauge needle and divided the specimen into two parts with one part placed in 20% (!) formalin and the other half placed in a cryopreservative solution and then froze... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4125295 Mon, 01 Nov 2010 11:45:00 +0100 4125295 http://www.medworm.com/index.php?rid=4119748&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F10%2Falk-inhibition-in-nsclc.html Great stuff in this week's NEJM! Today's (October 28, 2010) New England Journal of Medicine has no less than three articles reporting the use of small molecule ALK tyrosine kinase inhibitor crizotinib (PF-02341066, Pfizer) in non-small-cell lung cancers harboring the oncogenic fusion gene EML4-ALK and in a patient with ALK-rearrangement positive inflammatory myofibroblastic tumor, a distinctive but uncommon soft tissue neoplasm.   Pathologists should be familiar with these articles--at least so you can suggest appropriate testing for ALK rearrangement but also that you might "shine" at your next Tumor Conference ; )  BTW, the article by Kwak et al. presents in paper form the data that rocked this past summer's ASCO Annual Meeting regarding criz... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4119748 Fri, 29 Oct 2010 04:51:39 +0100 4119748 http://www.medworm.com/index.php?rid=4036956&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F10%2Ffollow-up-on-adenocarcinoma-with-bac-features.html My last post was a "Digital Case Challenge" presenting a case of pulmonary adenocarcinoma with non-mucinous bronchioloalveolar (BAC) features. Here's my synopsis of 3 recent papers on bronchioloalveolar carcinoma that focus on the clinicopathological, histological, and molecular differences between the two subtypes, non-mucinous and mucinous, as well as the practical importance in distinguishing these two subtypes. 1.  Wislez et al, in a recently published paper in Lung Cancer (2010;68:185-191), studied 50 cases of non-resectable adenocarcinoma with bronchioloalveolar (ADC-BAC) features who were enrolled in a multicenter study to evaluate gefitinib as a first-line therapy for non-resectable ADC-BAC.  Previous trials (SWOG S0126 and IFCT0401) have shown that ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=4036956 Wed, 06 Oct 2010 21:13:32 +0100 4036956 http://www.medworm.com/index.php?rid=3954493&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F09%2Fgrading-system-for-lung-adenocarcinoma-still-elusive.html The August 2010 issue of American Journal of Surgical Pathology features an article from the Memorial Sloan Kettering Cancer Center group proposing a grading system for lung adenocarcinoma in stage 1 cancer. Sica G, Yoshizawa A, Sima CS, et al.  A grading system of lung adenocarcinoma based on histologic pattern is predictive of disease recurrence in stage I tumors.  Am J Surg Pathol 2010;34:1155-1162. The authors articulate the frustration pathologists experience in dealing with the histological heterogeneity of lung adenocarcinoma (ACa) since the vast majority are mixed subtype as well as the lack of an objective, clinically relevant grading system for lung ACa.  Recent literature has shown that mixed subtype tumors with solid or micropapillary components appear to ha... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3954493 Thu, 09 Sep 2010 11:20:00 +0100 3954493 http://www.medworm.com/index.php?rid=3943036&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F09%2Fprognostic-factors-in-t1-colorectal-adenocarcinoma.html A frequently encountered specimen is the adenocarcinoma with submucosal invasion arising in a dysplastic adenomatous polyp or sessile lesion that has been resected endoscopically.  While much effort is directed at determining margin adequacy and depth of invasion, less attention has been given to other parameters that may be associated with risk of lymph node (LN) metastasis. Measuring the depth of invasion is frequnetly problematic given the morcellated nature of most specimens.  Generally, if the lesion is felt to be adequately excised, a formal colectomy may not necessarily be needed since the risk of LN metastasis in a T1 tumor is felt to be too low to warrent the morbidity of a colectomy. A recent article in the August 2010 Modern Pathology sought to detect patients at hig... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3943036 Tue, 07 Sep 2010 11:40:00 +0100 3943036 http://www.medworm.com/index.php?rid=3934619&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F09%2Fuse-of-oncology-decision-aids-by-patients.html Medscape reported on an article from J Clin Oncol that I thought was most curious: September 1, 2010 —The use of decision aids by physicians caring for cancer patients is "low", say the authors of a Canadian study. Only 24% of general surgeons, medical oncologists, and radiation oncologists in Ontario report using the aids, which are information guides that help patients make choices about cancer treatment. The study, based on a survey of clinicians, was published in the May issue of the Journal of Clinical Oncology (2010;28:2286-2292). However, in a letter published online August 30 in the journal, a German researcher raises an interesting possibility: that patients might be using decision aids at higher rates. In other words, patients might be adapting this clini... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3934619 Sat, 04 Sep 2010 13:00:00 +0100 3934619 http://www.medworm.com/index.php?rid=3767335&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F07%2Fmucinous-bronchioloalveolar-carcinoma-of-lung-and-alk-mutation.html In this study, 96% of responders had adenocarcinoma histology--primarily signet ring morphology.This is surely a very exceptional case since mucinous ACa/BAC is a very distinctive histological subtype and has been also characterized at the molecular level as being associated with KRAS mutation.  The point is that histology is not a perfect predictor of potentially druggable molecular pathologies.  If targeted therapy is being contemplated in NSCLC, we should adopt a systematic approach to all NSCLC regardless of histology.  At this point, while we are identifying patients who may potentially benefit from targeted therapy, we are building a database that will allow a more full appreciation of the relationship between histological type and molecular pathology.Thanks t... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3767335 Tue, 20 Jul 2010 04:06:14 +0100 3767335 http://www.medworm.com/index.php?rid=3740847&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F07%2Fp53-in-tumorassociated-fibroblasts-in-invasive-ductal-carcinoma.html Hasebe et al. have authored an interesting article in a recent Modern Pathology (2010;23:662-672) which builds on their earlier work that showed P53 expression in tumor-stromal fibroblasts (TSF) not forming fibrotic foci to be an important predictor of outcome in patients with invasive ductal carcinoma.The fibrotic focus has been shown to be a prognostic factor in breast cancer.  Moreover, criteria for fibrotic foci proposed by Van den Eynden et al. in 2007 (Dr. Hasebe was a co-author) appear to both clinically significant and reproducible in daily practice.  I am surprised that the use of this feature has not been adopted for routine use since presenting breast cancer cases with prominent fibrotic foci never fails to elicit curiosity and questions in Tumor Board.  Furthe... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3740847 Sat, 10 Jul 2010 03:04:53 +0100 3740847 http://www.medworm.com/index.php?rid=3534130&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F05%2Fthe-battle-is-on-news-from-aacr-2010.html Well it has taken me a couple weeks to study and digest the results of the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) clinical trial reported the week before last at the Annual Meeting of the American Association for Cancer Research (AACR).Although this is a small phase 2 study, I think it is important to note for pathologists because of the innovative design that incorporated a requirement for a second biopsy at the time of enrollment for the sake of tissue analysis.  This is a major issue of note.  First, it overcomes one of the major problems that I encounter as a lung cancer researcher--the lack of available tissue for those patients who end up being deemed inoperable after diagnostic bronchoscopic or CT-guided biopsy and ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3534130 Wed, 05 May 2010 03:52:30 +0100 3534130 http://www.medworm.com/index.php?rid=3511801&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F04%2Ferpr-testing-guidelines-joint-capasco-recommendations.html The College of American Pathologists (CAP) and the American Society of Clinical Oncology (ASCO) issue a joint guideline on April 19, 2010 in an effort to improve the accuracy of immunohistochemistry testing for estrogen (ER) and progesterone receptors (PgR) expression in breast cancer. This is similar to the joint effort the groups made with HER2 testing guideline in 2007.  The guideline is being published in the April 19 issues of ASCO’s Journal of Clinical Oncology (JCO) and the CAP’s Archives of Pathology & Laboratory Medicine in June 2010 but is available in electronic form here.  The ASCO Web page on the guidelines (http://www.asco.org/guidelines/erpr) has links to the unabridged version (yikes!) as well as downloadable slides.The major recommendation are sum... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3511801 Wed, 28 Apr 2010 04:55:02 +0100 3511801 http://www.medworm.com/index.php?rid=3408672&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F03%2Fmolecular-markers-for-targeted-therapy-in-lung-cancer-uscap-2010.html I attended the Special Course at USCAP 2010, "Basic Principles and Practice of Molecular Pathology in Cancer."  One of the talks was given by Dr. Marc Ladanyi from MSKCC and one of the leaders in the field of molecular pathology of lung cancer.  The title of his presentation was "Molecular Predictive Markers for Targeted Therapies in Lung Cancer."  Here's my "take-home" points from the talk: Term: "lung adenocarcinoma oncogenome"--(I like this) and he presented a pie chart illustrating the different (and (generally) mutually exclusive) mutations found so far in lung ACa  KRAS EGFR BRAF ERBB2 (HER2) ALK fusions (especially, ALK-EML4) MEK1 NF1 but still about one-third of lung ACa have an unknown mutation Although there a... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3408672 Fri, 26 Mar 2010 15:04:27 +0100 3408672 http://www.medworm.com/index.php?rid=3318684&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F03%2Ftrastumuzab-approved-for-treatment-of-her2positive-.html from primeLines:"On December 17, 2009, Roche’s trastuzumab (Herceptin®) received a positive recommendation from the European Medicines Agency (EMEA) for use in combination with standard chemotherapy for the treatment of previously untreated patients with HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction. The positive opinion for this new indication was issued in record time due to high unmet medical need and data from the ToGA trial (my emphasis), which demonstrated an increase in overall survival (OS) for patients with advanced HER2-positive gastric cancer who received trastuzumab plus chemotherapy (intravenous fluorouracil or capecitabine and cisplatin) compared to chemotherapy alone."I have done the immunostain for HER2 routinely on the las... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3318684 Mon, 01 Mar 2010 18:20:20 +0100 3318684 http://www.medworm.com/index.php?rid=3189434&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F01%2Fasco-recommendations-for-genetic-testing.html ASCO Releases Updated Policy Statement on Genetic TestingASCO issued its latest recommendations for genetic testing for cancer susceptibility. The updated statement addresses new developments during the past seven years, including the availability of genetic tests of unproven clinical benefit and direct-to-consumer (DTC) genetic testing. Read the press release, visit Cancer.Net for information for your patients, and read the statement in JCO.The comments relating to DTC genetic testing are worth reading this alone.  Marketing directly to consumers places us pathologists even more out of the loop given how in recent years, sales reps for test manufacturers have bypassed the lab and marketed directly to clinicians (e.g. ThinPrep, SurePath, OncotypeDx,). &#... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3189434 Wed, 20 Jan 2010 02:19:45 +0100 3189434 http://www.medworm.com/index.php?rid=3176138&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F01%2Frelationship-between-growth-patterns-and-survival-in-nsclc-news-from-aacriaslc.html Medscape (registration required) reports a study presented at the joint American Association for Cancer Research-International Association for the Study of Lung Cancer (AACR-IASLC) in which Sardari Nia et al from University of Antwerp, Belgium in which researchers from the University of Antwerp, Belgium identify tumor growth patterns in lung cancer that are independent predictors of disease-free survival, disease-specific survival, and overall survival.They report having previously identified three growth patterns--destructive, alveolar, and papillary.  These patterns do not describe histological subtypes (despite the confusing terminology).  The "papillary" type ("normal lung tissue is preserved in the presence of a new microenvironment") seems to be ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3176138 Fri, 15 Jan 2010 04:12:50 +0100 3176138 http://www.medworm.com/index.php?rid=3167477&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F01%2Fnodal-staging-score-a-tool-to-assess-adequate-staging-of-node-negative-colon-cancer----g%25C3%25B6nen-et-al-27-36-6166----journa.html Gonen, Schrag and Weiser recently report a study of colorectal cancer patients from the 1994-2005 SEER database to quantify the likelihood that a node-negative patient is, in fact, node-negative.  This is an interesting alternative method of assessing adequate staging of CRC in contrast to the usual "one-size-fits-all" minimum lymph node criteria (namely, 12).  They have developed a "nodal staging score" (NSS) that expresses the probability of a patient being "true negative" and find that this score depends on the T stage.  Overall, the probability of missing a positive node that is actually present is 29.7% if only 5 nodes are examined; 20.0% if eight are examined; 13.6% if 12 nodes are examined.  However, for a NSS of 90% (that is, a ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3167477 Tue, 12 Jan 2010 20:32:02 +0100 3167477 http://www.medworm.com/index.php?rid=3142860&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2010%2F01%2Fmini-case-report-early-serous-carcinoma-in-fallopian-tube-in-brca2-carrier.html The patient is a 63 year-old woman with a family history of ovarian cancer in her mother and breast cancer in a sister.  She has no personal history of cancer but is a BRCA2 mutation carrier .  She is otherwise asymptomatic and presented for risk-reducing total hysterectomy with bilateral salpingo-oophrectomy. The gross examination of the uterus was normal.  Both fallopian tubes were also normal and both ovaries appeared atrophic with few simple cysts.  The ovaries and fallopian tubes were examined and submitted for histology according to the SEE-FIM protocol where the ovaries and fallopian tubes are submitted in their entirety for histological examination.  The H&E images below were found in one fibria from the distal end of one fallopian tube.  (Y... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3142860 Mon, 04 Jan 2010 22:30:51 +0100 3142860 http://www.medworm.com/index.php?rid=3083203&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F12%2Fnew-therapeutic-approaches-for-sclc.html This article specifically discusses agents targeting the bcl-2 protein family.  The prognosis for SCLC remains pretty dismal but there is a lot of interest in this malignancy because of the better understanding of pathways involved in SCLC and the development of "targeted" therapies.Hurwitz J, McCoy F, Scullin P, Fennell D. New advances in the second-line treatment of small cell lung cancer. Oncologist. 2009;14(10):986-994. (Source: The Daily Sign-Out) The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3083203 Sun, 13 Dec 2009 16:11:59 +0100 3083203 http://www.medworm.com/index.php?rid=3083204&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F12%2Fleave-well-enough-alone.html The standard of care for treatment of mCRC has been surgical resection followed by adjuvant chemotherapy.  In patients presenting with symptomatic mCRC, palliative surgery is performed for bleeding, obstruction, or perforation, while in patients presenting with non-emergent symptoms and limited disease, surgery may be undertaken with a curative intent.  The role and value of surgery in patients with unresectable stage 4 colon cancer and a synchronous asymptomatic primary tumor is being currently investigated by the National Surgical Adjuvant Breast and Bowel Project in a prospective phase II study (NSABP C-10).  Current recommendations for treatment of mCRC are: Patients with evidence of significant obstruction, perforation, or uncontrolled bleeding shou... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3083204 Sun, 13 Dec 2009 16:02:12 +0100 3083204 http://www.medworm.com/index.php?rid=3067327&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F12%2Fmore-recommendations-for-lymph-node-adequacy-in-crc.html The Dutch National Working Group on Gastrointestinal Cancers has recently released colorectal cancer guidelines which includes a recommendation of a minimum of 10 lymph nodes to establish a negative lymph node status.  At the same time, the group states that "determining the lymph node status of a patient requires evaluation as many lymph nodes as possible using conventional techniques." (emphasis mineThe discussion of this recommendation states that "no definitive criteria were found in the literature regarding the minimum number of examined lymph nodes.  There is no evidence to support 12 lymph nodes, as recommended by TNM." (emphasis mine)Furthermore, they specifically do not recommend using immunohistochemistry to detect metastases or pre-treatment of me... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=3067327 Mon, 07 Dec 2009 19:56:40 +0100 3067327 http://www.medworm.com/index.php?rid=2901846&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F10%2Frecent-lecture-on-role-of-kras-mutation-in-management-of-colorectal-cancer.html I recently gave a Tumor Board presentation on the role of KRAS mutation testing in the management of colorectal cancer.  The PowerPoint file is attached for educational purposes.  I hope you will find it of interest.Download K-ras lecture upload (Source: The Daily Sign-Out) The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2901846 Fri, 16 Oct 2009 22:16:21 +0100 2901846 http://www.medworm.com/index.php?rid=2872082&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F10%2Fnovel-classification-for-gastric-cancer.html A multi-institutional study published online on Oct. 1 in PLoS Genetics examined 301 gastric carcinomas using gene expression profiles and a pathway prediction model to identify major oncogenic pathways involved in gastric cancer and relate expression of these pathways to patient survival.  They found proliferation/stem cell-related, Wnt/beta-catenin, and NF-kappaB pathways are deregulated in over 70% of the gastric cancers they studied.  Furthermore, the found patterns of pathway co-activation associated with survival.  This is a free access paper so please download and read.Reading the "Materials and Methods" of this paper is worthwhile in itself because the strategy the authors used is well-conceived and explained.  More importantly, this study demonstr... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2872082 Wed, 07 Oct 2009 03:13:40 +0100 2872082 http://www.medworm.com/index.php?rid=2774931&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F09%2Feuropean-congress-of-pathology-annual-meeting.html Clipped from The Dark Daily report:"Next to speak was Bent Ejlertsen, M.D., Ph.D., of the Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. The title of his presentation was “Prediction of Responsiveness to Adjuvant Anthracyclines in High-Risk Breast Cancer Patients.” He reported on the extensive studies about the TOP2A marker that he and his colleagues have conducted. Their goal was to learn how to use this biomarker for both prognostic and predictive evaluations to identify which breast cancer patients would benefit from therapy with adjuvant anthracyclines. The TOP2A marker is scored in a similar fashion as the HER2 marker. Ejlertsen stressed that improved patient safety would result as the pathology profession achieved more ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2774931 Tue, 08 Sep 2009 16:12:39 +0100 2774931 http://www.medworm.com/index.php?rid=2712382&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F08%2Fmir21-in-lung-cancer-in-never-smokers.html With all the recent ink on EGFR mutations in lung cancer and response to targeted TKIs, I thought that a recent paper by Seike et al (link to abstract, full text requires access) in the July 21, 2009 PNAS was interesting because they examined 28 cases of lung adenocarcinoma in never smokers by microRNA expression profiling and found that changes in previously identified miRNA expression (e.g. upregulated miR-21) were exaggerated in cases with EGFR mutations compared with those without mutations.In addition, they found a significant correlation between pEGFR and miR-21 expression in lung adenocarcinoma cell lines and suppression of miR-21 by an EGFR-TKI.  They also showed induction of apoptosis in both EGFR mutated and wild-type lung adenocarcinoma cell lines with antisense miRNA-21--... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2712382 Tue, 18 Aug 2009 19:23:31 +0100 2712382 http://www.medworm.com/index.php?rid=2695645&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F08%2Fthe-role-of-cypd6-inhibitors-with-tamoxifen.html I have seen a few requests for send-out genotype testing for CYPD6, the cytochrome P450 enzyme in localized to the liver that converts tamoxifen to its active metabolite, endoxifen.  In my post-ASCO meeting mop-up, one of the ResearchtoPractice 5-Minute Journal Club's called to my attention two abstracts from that meeting studying the impact of CYPD6 inhibitors on breast cancer recurrence in patients receiving tamoxifen.Both of these studies have significant methodological problems that limit the significance of their conclusions but they nevertheless are important to be aware of because they point out the potential pharmacological interaction between SSRIs and tamoxifen and the possible effects of that interaction on breast cancer recurrence and adherence to tamoxifen therapy.&#... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2695645 Thu, 13 Aug 2009 13:00:00 +0100 2695645 http://www.medworm.com/index.php?rid=2630398&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F07%2Fcolorectal-cancer-more-lymph-nodes-not-necessarily-better.html I pulled the following from ASCO Daily News.  I haven't read the full paper myself and, although not surprised by this study's results, I think this will likely be a good paper to use in discussions with surgical and oncologist colleagues.HealthDay (7/20, Thomas) reported, "More isn't necessarily better when it comes to surgically removing lymph nodes to diagnose late-stage colorectal cancer," according to a study published July 20 in the Archives of Surgery. The World Congress of Gastroenterology recommends removing "at least 12 lymph nodes during surgery for colorectal cancer," a standard that has been "widely adopted as a measure of quality in surgical practices."         That benchmark was also ... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2630398 Thu, 23 Jul 2009 04:32:35 +0100 2630398 http://www.medworm.com/index.php?rid=2630399&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F07%2Ffda-changes-labeling-for-cetuximab-and-panitumumab.html Finally, the FDA announced labeling changes to the anti-EGFR MoAbs cetuximab and panitumumab to reflect the overwhelming evidence supporting the benefit to patients receiving these drugs only with wild-type KRAS (recent CAP Today article).Although still limited to patients with metastatic colorectal cancer, I suspect there will be more uptake of KRAS mutation testing since there was still some confusion out there on the "best" way to test for EGFR because of the delay of the FDA to change the labeling--months after NCCN and ASCO changed their guidelines.Pathologists, oncologists, and patients should inquire about which methodology is being used because there are some critical differences. (Source: The Daily Sign-Out) The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2630399 Thu, 23 Jul 2009 01:44:56 +0100 2630399 http://www.medworm.com/index.php?rid=2606244&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F07%2Frelapserelated-molecular-signature-for-lung-adenocarcinoma.html I came across an intriguing study in J Clin Oncol (link to abstract) where a group from Nagoya University Graduate School of Medicine in Japan have developed a genetic signature to identify patients with lung adenocarcinoma with a high probability of relapse.  They analyzed whole-genome expression profiles in 117 lung adenocarcinoma specimens using microarrays and identified a relapse-related molecular signature based on 82 probes on a training set of 60 patients specimens.  This signature was then validated with several independent data sets.  The most interesting subset is 30 stage 1 patients who underwent surgery and were sorted into high- and low-risk for relapse; the high-risk group all relapsed and died within the 5 year follow-up period.This is one of numerous (and... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2606244 Thu, 16 Jul 2009 03:39:59 +0100 2606244 http://www.medworm.com/index.php?rid=2390450&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F05%2Fpetacc3-study-and-correlation-of-molecular-markers-with-stagespecific-prognosis.html The Pan-European Trials in Alimentary Tract Cancers (PETACC-3) is a large phase III randomized trial that yielded pathologic samples evaluable for IHC and molecular testing from 1404 patients with stage II/III cancer in a substudy to correlate various markers with stage-specific prognosis.  The markers evaluated included p53, SMAD4, thymidylate synthase, telomerase, MSI, 18q LOH, KRAS mutation, and BRAF mutation.The study compared 420 stage II patients and 984 stage III patients.  The most interesting finding from this substudy is strikingly different changes in marker expression between the two groups.  This suggests that stage II and stage III CRC develop through distinctly different molecular pathways and, thus, may represent different biological and clinico-pathologic... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2390450 Wed, 06 May 2009 20:32:37 +0100 2390450 http://www.medworm.com/index.php?rid=2365472&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F04%2Froutine-egfr-testing-in-lung-cancer.html I attended the Cecil A. Krakower Memorial Lecture at University of Illinois at Chicago on Saturday, April 18 and was treated to an informative lecture on EGFR-targeted therapy in lung cancer by Dr. Odile David from U of I/Chicago.  I have followed this with interest on a parallel track with KRAS mutations in colorectal cancer (recent CAP NewsPath article) and this lecture prompted some consideration of this issue.Although we have performed an immunohistochemical stain for EGFR on a few NSCLC tumors the past couple years, we have had few requests for EGFR assessment.  Based on discussions at Tumor Board, it would seem that our patients are treated with conventional platinum-based chemotherapy in the adjuvant setting, usually carboplatin with paclitaxel or docetaxel or vinorelbin... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2365472 Thu, 23 Apr 2009 20:09:38 +0100 2365472 http://www.medworm.com/index.php?rid=2349756&cid=t_167721_155_f&fid=38412&url=http%3A%2F%2Fpathlabmed.typepad.com%2Fsurgical_pathology_and_la%2F2009%2F03%2Fpreview-of-nccn-report-on-erpr-testing.html From the National Comprehensive Cancer Network (NCCN) 14th Annual Conference, March 14, 2009.  A NCCN task force will be issuing a recommendations on ER/PR testing in breast cancer in a report, "Integration of ER/PR Tumor Markers Into Treatment Planning for Breast Cancer" sometime in 2009 according to MedscapeNews.  Although it doesn't seem controversial that they should "recommend" mandatory ER/PR testing for invasive breast cancer (does anyone not do this?!) or optional testing for DCIS, these appear to be the main points.However, in an interview with Medscape Oncology, Dr. D. Craig Allred, one of the NCCN panel members, discusses some important issues with regard to ER/PR testing by immunohistochemistry (IHC).  These bear repeating once again be... The Daily Sign-Out blogs http://www.medworm.com/rss/comments.php?id=2349756 Mon, 23 Mar 2009 21:39:34 +0100 2349756 http://www.medworm.com/index.php?rid=1196090&cid=t_167721_136_f&fid=36032&url=http%3A%2F%2Fblog.healthtalk.com%2Fbreast-cancer%2Flife-with-breast-cancer%2Fthe-world-needs-nicole-a-reminder-about-cancer-genetics-risk-assessment%2F Have I told you about my niece Nicole? She is an amazing young woman. At 4-years-old, she was diagnosed with acute leukemia and suffered a lengthy treatment protocol. Her teenage years had her battling with the after effects of treatment but that in no way impinged on her ability to be a leader in her school and a peer counselor. She developed a love of music and a passion for African orphans. She spent her school breaks volunteering in an orphanage in Africa and only tolerated a year at university before she gave in to the desire to live among the children in the orphanage halfway around the world. They were so delighted they helped build a mud hut all her own for her to live in. One of her jobs was to name the young children that were brought to the group of huts and buildings that made ... Life with Breast Cancer blogs http://www.medworm.com/rss/comments.php?id=1196090 Sat, 02 Feb 2008 00:05:38 +0100 1196090 http://www.medworm.com/index.php?rid=1086073&cid=t_167721_136_f&fid=36051&url=http%3A%2F%2Ffeeds.b5media.com%2F%7Er%2Fb5media%2FCancerCommentary%2F%7E3%2F198428925%2F This study is the first step in developing a test that would allow us to sample a patient’s blood and determine whether more invasive testing and treatment are necessary. Using the four markers, known as CEA, RBP, SCC and AAT, we were able to distinguish patients who had cancer from those who didn’t with over 80 percent accuracy.” The four blood proteins: CEA, RBP, SCC and AAT – have been found in significantly different levels in patients with lung cancer as compared to patients of the same age and gender who didn’t have cancer. Find more details from Duke University Medical Center. Share This (Source: Cancer Commentary) Cancer Commentary blogs http://www.medworm.com/rss/comments.php?id=1086073 Tue, 11 Dec 2007 05:06:05 +0100 1086073