Expression of CK14, CK8/18 and IMP3 in BRCA-Related Invasive Breast Carcinomas
Farnaz Dadmanesh, Sambit K Mohanty, Ora Gordon, Shikha Bose. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Certain immunohistochemical markers are shown to be useful in predicting BRCA mutation status in invasive breast carcinomas (IBC). Our study aims to evaluate expression of CK8/18 (luminal), CK14 (basal), and IMP3 (marker of aggressiveness and progression) to predict BRCA mutation status in IBC.
Design: Of 105 patients with BRCA germline mutation who underwent mastectomy, 30 IBC cases were identified. 73% (n=22) were BRCA1, 24% (n=7) BRCA2 and 3% (n=1) with dual BRCA1/BRCA2 mutation. All cases were invasive ductal carcinoma (IDC), except for one BRCA1 tumor with invasive lobular carcinoma in the contralateral breast. Our control group included 27 sporadic IBC. Immunostaining for CK14, CK8/18 and IMP3 were performed in all cases. Staining results were recorded in semiquantitative fashion as strong and diffuse cytoplasmic (CK14 and CK8/18) and/or membranous (IMP3) staining. Statistical analyses were performed using logistic regression and Fischer's exact test.
Results: Of BRCA1 carcinomas, 2 were Modified Bloom-Richardson grade I, 5 grade II and 15 grade III. Of BRCA2 carcinomas, 2 were grade II and 5 grade III. The dual BRCA1/BRCA2 carcinoma was grade II. Interestingly, 54% (n=12) of BRCA1 carcinomas had luminal A, 5% (n=1) luminal B, and 41% (n=9) basal-like phenotype. Of the BRCA2 carcinomas, 71% (n=5) had luminal A and 29% (n=2) basal-like phenotype. The dual BRCA1/BRCA2 carcinoma had luminal A phenotype. In the control group, 11% (n=3) were grade I, 48% (n=13) grade II, and 41% (n=11) grade III. 44% (n=12) of sporadic IBC had luminal A, 19% (n=5) luminal B, 4% (n=1) HER-2/neu, and 33% (n=9) basal-like phenotype. The IHC results are summarized in Table 1. CK8/18 expression in sporadic IBC was significantly higher than the BRCA carcinomas (Fisher's exact test, p=0.015). No significant differences were observed between the study and control group for IMP3 and/or CK14.
|IBC||IMP3 positive||CK14 positive||CK8/18 positive|
|BRCA1 (n=22)||7 (32%)||8 (36%)||15 (68%)|
|BRCA2 (n=7)||1 (14%)||1 (14%)||6 (86%)|
|BRCA1/BRCA2 (n=1)||0 (0%)||1 (100%)||1 (100%)|
|Sporadic (n=27)||4 (15%)||5 (19%)||27 (100%)|