BRCA1 Immunohistochemical Staining as a Prognostic Indicator in Uterine Serous Carcinoma

Abstract

Our study illustrates that a low level of BRCA1 protein expression is a favorable prognostic indicator in USC, similar to what is observed in high-grade serous ovarian carcinoma. Further studies should focus on the BRCA1 status of USCs at a molecular level and also investigate whether BRCA1 protein expression is associated with response to chemotherapy in USC.

The molecular and genetic basis of inherited cancer risk in gynaecology

“…Some groups have suggested that patients with BRCA1 or BRCA2 germline mutations may be at increased risk of developing uterine serous carcinomas . Research from our own group has definitively shown that a low level of BRCA1 immunohistochemistry is a favourable prognostic indicator in serous cancers of the endometrium, similar to what is seen in high grade serous fallopian tube/ovarian carcinoma …”

“…Uterine serous carcinomas are morphologically virtually identical to their high grade serous fallopian tube/ovarian counterparts. 34 However, there remains some debate about the association of germline BRCA mutations and serous carcinoma of the endometrium. This area remains significantly underinvestigated with most studies suggesting that there is no association with BRCA mutation.…”

“…36 Research from our own group has definitively shown that a low level of BRCA1 immunohistochemistry is a favourable prognostic indicator in serous cancers of the endometrium, similar to what is seen in high grade serous fallopian tube/ ovarian carcinoma. 34,37 BRCAness BRCAness in ovarian cancer defines those sporadic cases that phenotypically resemble BRCA-mutated ovarian cancer often with genetic alterations that affect BRCA function and HR. Somatic mutations in BRCA1/2 occur in 5-10% of ovarian cancers in the general population, however, aberrant promoter hypermethylation results in reduced expression of BRCA1 leading to functional deficiency in 11-35% of ovarian cancer patients 38,39 and an immunohistochemical assessment of epigenetic loss of BRCA1 has been shown in up to 90% of high-grade ovarian cancers.…”

“…Uterine serous carcinomas are morphologically virtually identical to their high grade serous fallopian tube/ovarian counterparts . However, there remains some debate about the association of germline BRCA mutations and serous carcinoma of the endometrium.…”

BRCA1 and MAD2 Are Coexpressed and Are Prognostic Indicators in Tubo-ovarian High-Grade Serous Carcinoma

“…31 BRCA1 staining was performed using the mouse anti-BRCA1 (AB-1) mouse monoclonal (MS110) antibody (Calbiochem, UK) at a 1:200 dilution as previously described. 14,41 Evaluation of BRCA1 and MAD2 Immunostaining Three BRCA1-and MAD2-stained slides (which were derived from 2 immediately adjacent tissue sections of the TMA) were scored independently by 3 observers (T.B., L.N., and W.G.M.). Only cores containing greater than 20% tumor were scored.…”