abstract: Importance of Histologic Subtype in the Staging of Appendiceal Tumors

Blogger's Note:  appendiceal cancer (cancer of the appendix) is not the only cancer where cell type histologic records are deficient eg. breast cancer; why it's important? many reasons: patients with dual malignancies, primary vs metastatic, borderline/invasive.....; as in ovarian cancer cell,  type/s are included in one's own individual pathology report/s

Abstract

Background

Malignant neoplasms of the appendix have different behavior based on their histologic subtypes in anecdotal series. Current staging systems do not capture the diversity of histologic subtypes in predicting outcomes.

abstract: Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples

AACR: Multiple Risk Factors Identified for Ovarian Cancer - in Meeting Coverage, AACR from MedPage Today

abstract: Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors (endometrioid/clear cell cell types) MSH2 MSH6 MLH1

Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors.

Abstract

OBJECTIVE: Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized.

METHODS: We characterized clinical features, tumor morphology and mismatch repair defects in all ovarian cancers identified in Swedish and Danish Lynch syndrome families.

RESULTS: In total, 63 epithelial ovarian cancers developed at mean 48 (range 30-79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented. The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed.

CONCLUSION: The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch syndrome typically presents at young age as early-stage, non-serous tumors, which implicates that a family history of colorectal and endometrial cancer should be specifically considered in such cases.

Diagnosis of Ovarian Carcinoma Cell Type is Highly Reproducible: A Transcanadian Study

Abstract:
Reproducible diagnosis of ovarian carcinoma cell types is critical for cell type-specific treatment. The purpose of this study was to test the reproducibility of cell type diagnosis across Canada. Analysis of the interobserver reproducibility of histologic tumor type was performed among 6 pathologists after brief training in the use of modified World Health Organization criteria to classify ovarian carcinomas into 1 of 6 categories: high-grade serous, endometrioid, clear cell, mucinous, low-grade serous, and other. These 6 pathologists independently reviewed a test set of 40 ovarian carcinomas. A validation set of 88 consecutive ovarian carcinomas drawn from 5 centers was subject to local review by 1 of the 6 study pathologists, and central review by a single observer. Interobserver agreement was assessed through calculation of concordance and kappa values for pair-wise comparison. For the test set, the paired concordance between pathologists in cell type diagnosis ranged from 85.0% to 97.5% (average 92.3%), and the kappa values were 0.80 to 0.97 (average 0.89). Inclusion of immunostaining results did not significantly improve reproducibility (P=0.69). For the validation set, the concordance between original diagnosis and local review was 84% and between local review and central review was 94%. The kappa values were 0.73 and 0.89, respectively. With a brief training exercise and the use of defined criteria for ovarian carcinoma subtyping, there is excellent interobserver reproducibility in diagnosis of cell type. This has implications for clinical trials of subtype-specific ovarian carcinoma treatments.

abstract/free full pdf access:P redictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies Cancers

"Abstract: Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer."
 ..........
"High grade serous tumors show particular differences in terms of their development, genetic alterations and prognosis. This has led to the classification of ovarian cancer into two types: type 1 tumors, which are low grade and slowly developing (endometrioid, mucinous and low grade serous tumors), and type 2 tumors, which rapidly progress (high grade serous). In addition, the association of biomarker expression with survival varies substantially between subtypes, and can easily be overlooked in whole cohort analyses. Although these data suggest substantial differences between subtypes, until recently ovarian carcinomas were typically approached as a monolithic entity by researchers and clinicians. This practice impeded progress in understanding the biology or improving the management of the less common ovarian carcinoma subtypes. To avoid this effect, each subtype within a cohort should be analyzed individually. Therefore, molecular classifiers of ovarian cancer are of high clinical relevance in the management of these cancer patients...." cont'd

abstract: Tumor Type and Substage Predict Survival in Stage I and II Ovarian Carcinoma: Insights and Implications

"Tumor grade has been the most accepted prognostic indicator of disease-specific survival among women with stage I and II ovarian carcinomas. Many investigators have included stage IB, grade 1 at diagnosis as low-risk disease and have suggested that women in this category should not receive adjuvant therapy. However, grading assignment appears to be unreliable because of problems with reproducibility and lack of consideration of biological differences between the different tumor types. Some investigators believe that classification based on tumor typing using new histopathological criteria was more reproducible than grade assignment and would more accurately reflect biological differences..."cont'd

Mucinous Adenocarcinoma Involving the Ovary: Comparative Evaluation of the Classification Algorithms using Tumor Size and Laterality

Editorial: The heterogeneity of epithelial ovarian cancer. Getting it right David M. Gershenson

Editorial
The heterogeneity of epithelial ovarian cancer
Getting it right

David M. Gershenson, MD *
Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
email: David M. Gershenson (DGERSHEN@mdanderson.org)

Abstract
Epithelial ovarian cancer is heterogeneous and comprises 4 major rare subtypes - mucinous, clear cell, low-grade serous, and endometrioid - all distinct from the more common high-grade serous carcinoma. Women with uncommon histotypes should be triaged to separate clinical trials.