Low-grade serous ovarian cancer: a unique disease

Schmeler, Kathleen M.; Gershenson, David M.

doi:10.1007/s11912-008-0078-8

Cited by 77 publications

(71 citation statements)

References 35 publications

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“…2), substantiates morphologic grade as an age-specific effect modifier. The results also affirm clinical impressions that invasive low-grade SOC typically are detected at a younger age than high-grade SOC (17,18). Even so, comparisons of Fig.…”

Section: Discussionsupporting

confidence: 81%

“…3) indicate that the prognosis for low-grade SOC detected in late stage was only marginally better than for high-grade SOC. This could reflect observations that low-grade SOC are less responsive to conventional genotoxic therapies than high-grade SOC (18). The interactions between aging and oncogenetic factors driving low-grade versus high-grade cancer cell migration and stage progression probably deserve further investigation (40).…”

Section: Discussionmentioning

confidence: 98%

“…High-grade SOCs represent the majority of invasive ovarian cancers (9)(10)(11), and typically show molecular signatures or DNA amplification associated with genetic instability (12)(13)(14)(15)(16). Low-grade SOCs, which can also spread progressively (17,18), have been associated with stable oncogenic mutations (KRAS or BRAF) that influence cell proliferation (2,19).…”

Section: Introductionmentioning

confidence: 99%

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Qualitative Age Interactions between Low-grade and High-grade Serous Ovarian Carcinomas

Grimley

Matsuno

Rosenberg

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Purpose: Ovarian epithelial carcinomas, including the predominant serous ovarian carcinoma (SOC) type, are heterogeneous malignancies. Even though invasive SOCs of low and high grade can be distinguished by morphology and molecular or immunohistochemical profiles, age-specific risks relevant to their separate carcinogenic pathways and clinical features have not been fully explored. Methods: In search of further clues to the etiology/pathogenesis of low-grade and high-grade SOCs, we analyzed incidence rate patterns. Case and age-adjusted population data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for years 1990 through 2005. Descriptive epidemiology for n = 19,899 cases was supplemented with age-period-cohort models fitted by grade. Results: SOC age-adjusted incidence rate ratios (IRR) of high to low grade (IRR H/L ) were <1.0 before age 40, and >1.0 thereafter. Accordingly, SOC age-specific incidence rates were also greater for low grade before age 40 years, and then greater for high grade. The reversals of IRR H/L , with crossings of the age-specific incidence rate near age 40 years occurred irrespective of early or late SOC stage. These results were reproducible and reliable in age-period-cohort models that were adjusted for period and cohort effects (P ≈ 0 for age interactions by grade). Conclusions: Robust qualitative age interactions between low-grade and high-grade SOC showed that grade is an age-specific effect modifier in these malignancies. With increasing research interest in identifying the genomic determinants of SOC risk, therapeutic response, and outcome, future analytic studies and clinical trials should be powered to account for age-dependent grade interactions. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2256-61)

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Qualitative Age Interactions between Low-grade and High-grade Serous Ovarian Carcinomas

Grimley

Matsuno

Rosenberg

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Low-grade serous carcinomas have been shown to be one of the histological types that shows a poor response to neoadjuvant chemotherapy. 13,15,36 Five out of six low-grade serous carcinomas in the current Tom Baker Cancer Centre cohort were classified as chemotherapy resistant. Although low-grade serous carcinomas are relatively uncommon, it comprise the second most-common histotype in the setting of advanced stage ovarian carcinoma after high-grade serous carcinomas.…”

Section: Discussionmentioning

confidence: 99%

The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors

et al. 2013

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Low-grade serous carcinomas and serous borderline tumors, combined herein and referred to as low-grade serous tumors, show distinct molecular alterations and clinical behaviors compared with high-grade serous carcinomas. The discrimination between low-grade serous tumors and high-grade serous carcinomas can be challenging on small tissue samples, such as cell blocks of paracentesis fluid or biopsies from omental disease. The purpose of this study was to test the ability of TP53 and CDKN2A immunohistochemistry to distinguish between high-grade serous carcinomas and low-grade serous tumors on small tissue samples. Tissue microarrays containing 582 high-grade serous carcinomas, 45 low-grade serous carcinomas, and 49 serous borderline tumors, confirmed by contemporary histopathological review, were stained for TP53 and CDKN2A (DO7 and E6H4 antibody clones, respectively). TP53 was scored as completely absent, wild-type pattern or overexpressed (460%), and CDKN2A was scored as either negative/patchy (o90%) or block expression (490%). The combination of the two markers, ie, the TP53 wild-type pattern and CDKN2A patchy expression, had sensitivity for low-grade serous tumors of 89%, a specificity of 93%, a positive predictive value of 68%, and a negative predictive value of 98%. These markers can, therefore, be used on small biopsies/ cell blocks to refute a diagnosis of low-grade serous tumors. These findings may inform emerging neoadjuvant therapeutic strategies in advanced ovarian cancers and may be crucial for future clinical trials on molecular-based therapies.

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“…Tumor cells from this group exhibit stem cell-like characteristics, as well as de-activating mutations in tumor suppressor genes p53 and breast cancer antigens 1 and 2 (BRCA1 and -2) as well as loss of heterozygosity (LOH) on chromosomes 7q and 9q (13). In contrast, low-grade serous EOCs exhibit a different distinct genetic profile, including oncogene-activating mutations in Kirsten rat viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), and phosphoinositide-3-kinase-catalytic α (PIK3CA), as well as LOH on chromosome Xq, microsatellite instability, and expression of amphiregulin (14).…”

mentioning

confidence: 99%