paywalled: Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients: from the Danish ‘MALOVA’ ovarian cancer study

Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients: from the Danish ‘MALOVA’ ovarian cancer study

The primary objective of this study was to assess the expression of cyclin E in tumour tissues from 661 patients with epithelial ovarian tumours. The second was to evaluate whether cyclin E tissue expression levels correlate with clinico-pathological parameters and prognosis of the disease. Using tissue arrays (TA), we analysed the cyclin E expression levels in tissues from 168 women with borderline ovarian tumours (BOT) (147 stage I, 4 stage II, 17 stage III) and 493 Ovarian cancer (OC) patients (127 stage I, 45 stage II, 276 stage III, 45 stage IV). Using a 10% cut-off level for cyclin E overexpression, 20% of the BOTs were positive with a higher proportion of serous than mucinous tumours. Sixty-two per cent of the OCs were positive for cyclin E expression with the highest percentage found in clear cell carcinomas. 

Results based on univariate and multivariate survival analyses with a 10% cut-off value showed that cyclin E had no independent prognostic value. In conclusion, we found cyclin E expression in tumour tissue to be of limited prognostic value to Danish OC patients.

Pathol. 2012 - abstract (Japan) "Piling up" clear cells in müllerian-type mucinous and mixed cell-type borderline tumor do not represent concomitant clear cell neoplasms (mucinous/mixed/clear cell/borderline/ER....)

Hum Pathol. 2012 Mar 19. [Epub ahead of print]

"Piling up" clear cells in müllerian-type mucinous and mixed cell-type borderline tumor do not represent concomitant clear cell neoplasms.

Abstract

The nature of "piling up" proliferation of clear cells in müllerian mucinous/mixed borderline tumor has not been well characterized. The purpose of this study was to clarify whether or not such clear cells represent concomitant clear cell neoplasms.

First, we carefully reviewed hematoxylin and eosin slides taken from 139 ovarian tumors diagnosed as clear cell carcinoma (112 cases) and müllerian mucinous/mixed borderline tumor (27 cases) to clarify (1) the frequency of piling-up clear cells in müllerian mucinous/mixed borderline tumor and (2) the frequency of the coexistence of typical clear cell carcinoma and müllerian mucinous/mixed borderline tumor.

Second, we investigated the immunohistochemical expression of estrogen receptor, hepatocyte nuclear factor-1β, and glypican-3 in proliferating clear cells in both tumors.

We identified piling-up clear cells in 56% of müllerian mucinous/mixed borderline tumors. Such clear cells lacked the severe nuclear atypia, complex branching, and dense hyalinized cores of typical clear cell carcinoma. We did not find coexistence of typical clear cell carcinoma and müllerian mucinous/mixed borderline tumor in any tumors.

Piling-up clear cells and endocervical-like mucinous cells were positive for estrogen receptor but negative for hepatocyte nuclear factor-1β and glypican-3. Most clear cell carcinomas showed a hepatocyte nuclear factor-1β-positive/estrogen receptor-negative immunophenotype, and about half of them were glypican-3 positive.

In conclusion, piling-up clear cells in müllerian mucinous/mixed borderline tumor do not represent concomitant clear cell neoplasms because clear cell carcinoma and müllerian mucinous/mixed borderline tumor hardly ever coexist and because such clear cells in both tumors are immunophenotypically distinct.

abstract - Identification of Cancer Patients with Lynch Syndrome: Clinically Significant Discordances and Problems in Tissue-Based Mismatch Repair Testing

Systematic Immunohistochemistry Screening for Lynch Syndrome in Early Age-of-Onset Colorectal Cancer Patients Undergoing Surgical Resection

This strategy identifies a substantial number of LS patients who would have been missed if genetic testing was based on the Amsterdam II Criteria alone.

Nuclear P27 (gene) expression in benign, borderline (LMP) and invasive tumors of the ovary and its association with prognosis: A GOG group study

Abstract

Objective

Nuclear p27 expression was examined in non-invasive and invasive ovarian tumors from a cross-sectional study, and clinical relevance of p27 was evaluated in the primary tumors from women participating in two randomized phase III treatment trials.

Methods

An immunohistochemistry assay was used to detect p27 in formalin-fixed paraffin-embedded ovarian tumors from 3 distinct sources.

Research Highlights

► Low p27 expression is associated with malignant transformation of the ovary.
► A cyclin E to p27 ratio > 1.0 may be associated with shorter survival.
► Study required confirming increased recurrences with low p27 in early stage patients.

abstract: The Clinical Molecular Diagnostics Laboratory and Microsatellite Instability Testing of Colorectal Cancer

Note: this abstract gives an overview of Lynch Syndrome testing eg. immunohistochemistry (testing of tumour); Microsatellite (MSI); improved survival rates, treatment options (relating to test results)

abstract/free full access: Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers -- Sjursen et al. -- Journal of Medical Genetics

Conclusion:
Amsterdam criteria and each of the Bethesda criteria were inadequate for identifying MSH6 mutation-carrying kindreds. MSH6 mutations may be more common than currently assumed, and the penetrance/expression of MSH6 mutations, as derived from families meeting current clinical criteria, may be misleading. To increase detection rate of MMR mutation carriers, all cancers in the Lynch syndrome tumour spectrum should be subjected to immunohistochemical analysis and/or analysis for microsatellite instability.

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.

Atypical identification of Lynch syndrome by immunohistochemistry and microsatellite instability analysis on jejunal adenocarcinoma

Note: abstract/free full text (pdf)
*this case describes a patient with many different cancers in the family including breast cancer, MSH6 deficiency

"LS (Lynch Syndrome) has been traditionally described in terms of earlyonset colorectal and endometrial cancers. Although this remains a confirmed association, we are learning more about the variability of LS and the prevalence of other cancers associated with this condition. The majority of cases of LS are reported to be caused by MLH1 and MSH2 gene mutations, but as evaluation for this condition becomes more widespread and routine in cases beyond the classically reported presentation, it is likely that we will come to find that the prevalence of other mismatch gene mutations is much higher than previously suspected."