NKX3.1 Expression in Primary Breast Carcinoma
Mark A Samols, Andrea Subhawong, Rajni Sharma, Peter B Illei, Pedram Argani, Ashley M Cimino-Mathews. Johns Hopkins Hospital, Baltimore, MD
Background: NKX3.1 functions as a tumor suppressor gene that is regulated by androgens and is downregulated in prostate cancer. Immunohistochemistry (IHC) for the NKX3.1 has been shown to be highly specific for prostatic-derived tumors and tissue; however, NKX3.1 expression has also been reported in a small number of breast carcinomas. Furthermore, NKX3.1 has been shown to inhibit estrogen receptor signaling (Cancer Res. 2008; 68:7380-5). Here, we investigate labeling of NKX3.1 in invasive ductal and lobular carcinomas of the breast with full characterization of ER, PR and Her-2 status.
Design: Tissue microarrays (TMAs) of primary invasive breast carcinomas were labeled by IHC for NKX3.1. The TMAs included 86 cases of invasive ducal carcinoma (IDC) and 37 cases of invasive lobular carcinomas (ILC). The IDC consisted of 20 luminal A, 7 luminal B, 14 Her-2 positive/ER negative, 32 basal like, and 13 unclassified ER/PR/Her2 triple negative carcinomas. The ILC consisted of 34 cases of luminal A and 3 cases of luminal B. The ILC included 3 cases with pleomorphic LCIS and 1 with histiocytoid features. NKX3.1 expression was scored as percentage nuclear positivity and staining intensity. Any amount of staining was considered positive.
Results: Nuclear NKX3.1 labeling was seen in 2 of 86 IDCs (2%), and 10 of 37 ILCs (27%). All cases were luminal A, one case of the positive ILC had pleomorphic features. Staining intensity was weak in all cases with variable percentages of cells demonstrating expression (1-100%). NKX3.1 positivity was seen only in ER- and PR-positive breast carcinomas, which showed a significant correlation (p=0.0002, Fisher exact test). Positive staining was also significantly associated with ILC (p<0.0001, Fisher exact test). Expression was not correlated with tumor stage, size, Her2 expression, presence of lymph node metastases or patient age.
Conclusions: Our study is the first to evaluate NKX3.1 expression in breast carcinomas with known ER, PR and Her-2 status. NKX3.1 immunolabeling was significantly associated with ILC and positive hormone receptor status. Further studies are needed to evaluate what role if any NKX3.1 plays in ER signaling and hormonal response in these neoplasms.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 20, Wednesday Afternoon