Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes

Abstract

Characteristic histopathologic features have been described in high grade serous carcinoma associated with BRCA abnormalities (HGSC-BRCA), which are known to have relatively favorable clinical outcomes. The aim of this study was to evaluate the clinical significance of invasion patterns in metastatic HGSC-BRCA cases. Thirty-seven cases of advanced stage HGSC with known BRCA1 or BRCA2 germline mutation were retrieved from our institutional files. Twenty-three patients had germline mutation of BRCA1 and 14 with BRCA2 mutation. The pattern of invasion at metastatic sites was recorded and classified as pushing pattern (either predominantly or exclusively), an exclusively micropapillary infiltrative pattern, or an infiltrative pattern composed of papillae, micropapillae, glands and nests (mixed infiltrative pattern). Histologic evaluation of metastases was performed without knowledge of genotype or clinical outcome. Clinical data were abstracted from medical records. Median age was 56 years (range, 31-73 years). All patients presented at stage IIIC or IV and underwent complete surgical staging followed by chemotherapy. All 37 HGSC-BRCA cases showed either pushing pattern metastases (30; 81%) or infiltrative micropapillary metastases (7;19%). No HGSC-BRCA cases exhibited metastases composed solely of mixed infiltrative patterns. Among the 7 infiltrative micropapillary cases, 6 had BRCA1 germline mutation vs 1 BRCA2. Median time of follow-up was 26 months (range, 13-49 months). All 7 patients with infiltrative micropapillary metastases either experienced recurrence or died of disease (5 recurrence and 2 deaths), which was significantly worse than patients with predominantly pushing pattern metastases, of whom 16 of 30 (53%) experienced recurrence (n=14) or died of disease (n=2); P value= 0.03. In conclusion, the recognition of different invasion patterns of metastatic extrauterine HGSC-BRCA has prognostic implications. The infiltrative micropapillary pattern is associated with poor outcomes and is more frequently seen in BRCA1 associated HGSC than in BRCA2 cases.

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