title: 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. Of the 37 cases of advanced-stage HGSC with known BRCA1 or BRCA2 germline mutation retrieved from our institutional files, 23 patients had a germline mutation of BRCA1 and 14 had a BRCA2 mutation. The pattern of invasion at metastatic sites was recorded and classified as a 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 to 73 y). 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 case exhibited metastases composed solely of mixed infiltrative patterns. Among the 7 infiltrative micropapillary cases, 6 had a BRCA1 germline mutation versus 1 with a BRCA2 mutation. The median time of follow-up was 26 months (range, 13 to 49 mo). All 7 patients with infiltrative micropapillary metastases either experienced recurrence or died of disease (5 recurrences and 2 deaths), which was significantly worse than what was seen in patients with predominantly pushing pattern metastases, of whom 16 of 30 (53%) experienced recurrence (n=14) or died of disease (n=2) (P=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.
authors.affiliation: *Department of Pathology †Department of Surgery, Division of Gynecology ‡Deparment of Medicine, Clinical Genetics Service ∥Department of Radiology, Memorial Sloan Kettering Cancer Center §Weill Cornell Medical College, New York, NY.
authors.forename: Yaser R
authors.initials: YR
authors.lastname: Hussein
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Ducie
authors.forename: Angela G
authors.initials: AG
authors.lastname: Arnold
authors.forename: Noah D
authors.initials: ND
authors.lastname: Kauff
authors.forename: Hebert A
authors.initials: HA
authors.lastname: Vargas-Alvarez
authors.forename: Evis
authors.initials: E
authors.lastname: Sala
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics* / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D010641:Phenotype; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor