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Background  Hepsin, (also called TMPRSS1) and TMPRSS3 are type II transmembrane serine proteases (TTSPs) that are involved in cancer progression. TTSPs can remodel extracellular matrix (ECM) and, when dysregulated, promote tumor progression and metastasis by inducing defects in basement membrane and ECM molecules. This study investigated whether the gene and protein expression levels of these TTSPs were associated with breast cancer characteristics or survival.    Methods  Immunohistochemical staining was used to evaluate hepsin levels in 372 breast cancer samples and TMPRSS3 levels in 373 samples.  TMPRSS1  mRNA expression was determined in 125 invasive and 16 benign breast tumor samples, and  TMPRSS3  mRNA expression was determined in 167 invasive and 23 benign breast tumor samples. The gene and protein expression levels were analyzed for associations with breast cancer-specific survival and clinicopathological parameters.    Results  Low  TMPRSS1  and  TMPRSS3  mRNA expression levels were independent prognostic factors for poor breast cancer survival during the 20-year follow-up ( TMPRSS1 ,  P  = 0.023; HR, 2.065; 95 % CI, 1.106–3.856;  TMPRSS3 ,  P  = 0.013; HR, 2.106; 95 % CI, 1.167–3.800). Low expression of the two genes at the mRNA and protein levels associated with poorer survival compared to high levels (log rank  P -values 0.015–0.042). Low  TMPRSS1  mRNA expression was also an independent marker of poor breast cancer prognosis in patients treated with radiotherapy ( P  = 0.034; HR, 2.344; 95 % CI, 1.065–5.160). Grade III tumors, large tumor size, and metastasis were associated with low mRNA and protein expression levels.    Conclusions  The results suggest that the TTSPs hepsin and TMPRSS3 may have similar biological functions in the molecular pathology of breast cancer. Low mRNA and protein expression levels of the studied TTSPs were prognostic markers of poor survival in breast cancer.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-015-1440-5) contains supplementary material, which is available to authorized users.

Low expression levels of hepsin and TMPRSS3 are associated with poor breast cancer survival