Prediction of BRCA1 Germ-Line Mutation Status in Patients with Breast Cancer Using Histoprognosis Grade, MS110, Lys27H3, Vimentin, and KI67

Abstract

Family structure, lack of reliable information, cost, and delay are usual concerns when deciding to perform BRCA analyses. Testing breast cancer tissues with four antibodies (MS110, lys27H3, vimentin, and KI67) in addition to grade evaluation enabled us to rapidly select patients for genetic testing identification. We constituted an initial breast cancer tissue microarray, considered as a learning set, comprising 27 BRCA1 and 81 sporadic tumors. A second independent validation set of 28 BRCA1 tumors was matched to 28 sporadic tumors using the same original conditions. We investigated morphological parameters and 21 markers by immunohistochemistry. A logistic regression model was used to select the minimal number of markers providing the best model to predict BRCA1 status. The model was applied to the validation set to estimate specificity and sensibility. In the initial set, univariate analyses identified 11 markers significantly associated with BRCA1 status. Then, the best multivariate model comprised only grade 3, MS110, Lys27H3, vimentin, and KI67. When applied to the validation set, BRCA1 tumors were correctly classified with a sensitivity of 83% and a specificity of 81%. The performance of this model was superior when compared to other profiles. This study offers a new rapid and cost-effective method for the prescreening of patients at high risk of being BRCA1 mutation carriers, to guide genetic testing, and finally to provide appropriate preventive measures, advice, and treatments including targeted therapy to patients and their families.

Estrogen promotes estrogen receptor negative BRCA1-deficient tumor initiation and progression

“…However, clinically hormone therapy prevents development and suppresses the progression of BRCA1 -deficient, ER-negative breast cancers [ 3 , 4 ]. Inspired by the finding that a fraction of BRCA1 -deficient human and mouse tumor cells harbor EMT features [ 16 – 19 , 22 – 24 , 39 , 44 ], and the finding that E2 enhanced the heterogeneity of p18 −/− ;Brca1 MGKO and p16 −/− ; Brca1 MGKO tumors with elevated squamous metaplasia and spindle-shaped cells (typical morphological characteristics of mesenchymal cells), we hypothesized that estrogen promotes EMT and stimulates BRCA1 -deficient, ER-negative tumorigenesis independent of ER. We found by western blot analysis that E2-treated p18 −/− ;Brca1 MGKO tumors expressed a higher level of EMT marker (Vim) and EMT-inducing transcription factors (EMT-TFs) including p-Fra1 and Snail, than placebo-treated tumors.…”

Poly(ADP-Ribose) Polymerase 1 (PARP1) Overexpression in Human Breast Cancer Stem Cells and Resistance to Olaparib

“…Möbus, University of Ulm, Ulm, Germany (BrCa-MZ-01) [6]. BRCA1 and BRCA2 gene status was checked for each cell line by full sequencing, as previously described [7]. The cell lines were grown using recommended culture conditions, as previously described [5].…”

Identification of recurrentBRCA1 mutation and its clinical relevance in Chinese Triple‐negative breast cancer cohort

“…Our data showed that the BRCA1 rs80350973 mutation is only associated with high Ki‐67 index in Chinese patients with TNBC ( P = 0.004). A previous study showed that overexpression of Ki‐67 was associated with BRCA1 mutation and was an indicator of poor prognosis in TNBC . Thus, we sought to determine if the rs80350973 mutation could contribute to shorter DFS.…”