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

伴BRCA胚系突变的高级别浆液性癌子宫外转移时的侵袭模式及与临床预后的相关性

Hussein YR,Ducie JA,Arnold AG,Kauff ND,Vargas-Alvarez HA,Sala E,Levine DA,Soslow RA

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.

摘要

BRCA异常的高级别浆液性癌(HGSC-BRCA)具有典型组织病理学特征,临床预后相对良好。本研究的目的是评估转移性HGSC-BRCA病例侵袭模式的临床意义。本研究纳入我们学院档案库的37例明确BRCA1或BRCA2胚系突变晚期HGSC,其中23名患者为BRCA1胚系突变,另14名为BRCA2突变。记录转移部位侵袭模式,分为推挤性模式(主要结构或全部结构),全部为微乳头浸润模式,或由乳头、微乳头、腺体和细胞巢组成的浸润性模式(混合性浸润模式)。组织学评估转移不考虑基因型或临床预后信息。临床数据摘自病历。中位年龄56岁(31-73岁)。所有患者表现为IIIc或IV期并行详尽的外科分期及化疗。所有37例HGSC-BRCA或者呈推挤性转移(30;81%),或为浸润性微乳头转移(7;19%)。无HGSC-BRCA病例显示仅由混合性浸润性模式组成的转移。7例浸润性微乳头病例中,6例为BRCA1胚系突变,1例为BRCA2突变。中位随访时间26个月(13-49个月)。7例浸润性微乳头转移病例均出现复发或死于该病(5例复发;2例死亡),显著差于主要为推挤性模式转移的患者,后者30例中仅16例(53%)出现复发(n=14)或死于该病(n=2)(p=0.03)。总之,识别HGSC-BRCA子宫外转移不同的侵袭模式有预后意义。浸润性微乳头模式与预后差有关,并更多见于BRCA1相关HGSC,而不是BRCA2相关病例。

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