Analysis of normal epithelial cell specific-1 (NES1)/kallikrein 10 mRNA expression by in situ hybridization, a novel marker for breast cancer

Purpose: Normal epithelial cell specific-1 (NES1)/kallikrein 10 gene is exp ressed in normal mammary and prostate epithelial cells, but the expression of NES1 mRNA and protein is markedly reduced in established breast and pros tate cancer cell lines although the NES1 gene is intact. Here, we wished to assess whether NES1 expression is downregulated in primary breast cancers. Experimental Design: We developed and used an in situ hybridization techniq ue with an antisense NES1 probe to detect NES1 mRNA in sections of normal b reast specimens, typical and atypical ductal hyperplasia, ductal carcinoma in situ, and infiltrating ductal carcinoma. Results. All of the 30 normal breast specimens showed high NES1 expression. Notably, 18 (75%) of 24 typical and atypical breast hyperplasia specimens showed high NES1 expression, with weak-to-moderate expression in 6 (25%). S ignificantly, 13 (46%) of 28 ductal carcinoma in situ specimens lacked NES1 expression, and the remaining 15 (54%) showed weak-to-moderate expression. Finally, 29 of 30 (97%) infiltrating ductal carcinoma grades I-III samples lacked NES1 mRNA, with weak expression in the remaining one sample. Conclusions: Our results demonstrate that NES1 mRNA is expressed in normal breast tissue and benign lesions, with loss of NES1 expression during tumor progression. We suggest that NES1 expression may serve as a molecular tool in the study of breast cancer progression. Studies with larger series of s pecimens should help assess whether NES1 expression can be a diagnostic and /or prognostic marker in breast and other cancers.