Invasion Patterns of Metastatic Pelvic High-Grade Serous Carcinoma Are Associated with BRCA Alterations
Carolina Reyes, Douglas A Levine, Robert Soslow. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: BRCA-associated high grade serous carcinoma (B-HGSC) is associated with relatively better clinical outcomes than sporadic HGSC, at least in part because of increased sensitivity to platinum chemotherapeutic agents. It has recently been reported that B-HGSC has a distinctive histologic appearance, characterized by solid and transitional cell-like architecture. Interestingly, ovarian transitional cell carcinoma has also been reported to be relatively prognostically favorable and chemosensitive; it has also been suggested that there is a tendency for peritoneal metastasis in the form of circumscribed nodular masses amenable to optimal debulking. We hypothesize that peritoneal metastatic B-HGSC is associated with characteristic morphologic features indirectly associated with favorable outcomes.
Design: The morphologic patterns of peritoneal metastatic sites were studied by reviewing 123 HGSC cases. Genetic subgroups represented were: BRCA1 germline mutation (n=13); BRCA1 somatic mutation (n=5); BRCA1 promoter methylation (n=10); BRCA2 germline mutation (n=5); BRCA2 somatic mutation (n=1); negative for BRCA1 germline mutation (n=20) and other HGSCs with no BRCA abnormality (n=69). Number of metastatic sites ranged from 1 to 9 (average of 4 per case). Tumor architecture (solid, cribriform/pseudoendometriod, papillary and pseudopapillary) and pattern of invasion (infiltrating vs pushing) were recorded for each metastatic site. Histologic evaluation of metastases was evaluated without knowledge of genotype.
Results: A pushing invasive pattern was seen in 24/34 (71%) metastatic cases with BRCA1 or BRCA2 abnormality, as compared with metastatic sites of negative BRCA1 germline or other high grade serous cases with no BRCA abnormality, which showed characteristically non-micropapillary, infiltrating invasion (89/89 cases, 100%). Micropapillary infiltration was found in 24% (8/34) of the metastatic sites with BRCA1 or BRCA2 abnormality as compared with no sites in the negative BRCA1 germline or other HGSC with no BRCA abnormality. Similar tumor architecture (solid, cribriform/pseudoendometriod and pseudopapillary) was found across all subgroups.
Conclusions: Patterns of invasion had greater association with BRCA abnormalities than tumor architecture. A pushing pattern of invasion is a highly prevalent and specific morphologic characteristic of metastases of pelvic HGSC with associated BRCA abnormality. This finding may have diagnostic, prognostic and therapeutic value if independently confirmed.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 8:45 AM
Platform Session: Section E, Tuesday Morning