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

Abstract

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)

A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions

“…From a morphologic perspective, the main differential diagnosis of epitheloid peritoneal MM in young patients is with serous carcinoma, although they tend to occur in females of older age (44). In contrast to high grade serous carcinoma, MM typically reveal a non-hierarchical papillary growth, with mild to moderate atypia and a relatively low mitotic activity.…”

Distribution and case-fatality ratios by cell-type for ovarian carcinomas: A 22-year series of 562 patients with uniform current histological classification

“…Serous carcinomas have been more clearly distinguished from endometrioid and clear cell carcinomas with which they have often been confused [13,14]. Serous carcinomas have also been divided into two distinct groups, low grade and high grade, which do not appear to be different grades of the same tumor, but rather, based on morphologic, molecular biologic and clinical outcome data, reflect different cell types [1,2,10,15,16]. Finally, mucinous carcinomas have been refined into intraepithelial carcinoma, invasive and metastatic groups.…”

Agreement for tumor grade of ovarian carcinoma: analysis of archival tissues from the surveillance, epidemiology, and end results residual tissue repository

“…The molecular classification of ovarian epithelial carcinomas as low grade (type I) or high grade (type II) identifies two sets of cancers with contrasting incidence, molecular characteristics, and clinical outcomes (1–7). The importance of ovarian cancer grade also transcends relevance for individuals with implications for cancer epidemiology and surveillance.…”

“…Malpica and colleagues at the M.D. Anderson Cancer Center proposed a two-tier system (low or high grade; herein referred to MDACC) for serous ovarian carcinomas (12–15), which is based upon a dualistic conceptual framework where low and high grade carcinomas proceed along two separate cancer pathways (1–7). …”