Expression of GHRH-R, a Potentially Targetable Biomarker, in Triple-negative Breast Cancer

Abstract

Growth hormone-releasing hormone (GHRH) has been shown to modify the growth behavior of many cancers, including breast. GHRH is produced by tumor cells, acts in an autocrine/paracrine manner, and requires the presence of GHRH receptor (GHRH-R) on the tumor cells to exert its effects. GHRH activity can be effectively blocked by synthetic antagonists of its receptor and hence, the expression of GHRH-R by tumor cells could serve as a predictor of response to GHRH-R antagonist therapy. In this study, we investigated the expression of GHRH-R in triple-negative breast cancers (TNBC). As TNBCs are morphologically and immunophenotypically heterogenous, the staining results were also correlated with the histologic subtypes of these tumors. On the basis of histomorphology and immunophenotype, 134 cases of primary TNBCs were further subdivided into medullary, metaplastic, apocrine, and invasive ductal carcinomas of no special type (IDC-NST). Immunohistochemistry for GHRH-R was performed on paraffin sections and the staining results were assessed semiquantitatively as negative, low expression, moderate, and high expression. Of the 134 TNBCs, 85 were classified as IDC-NST, 25 as metaplastic, 16 as medullary, and 8 as apocrine carcinoma. Overall, positive reaction for GHRH-R was seen in 77 (57%) of tumors including 66 (77.6%) of IDC-NST. All medullary carcinomas were negative for GHRH-R and, with the exception of 1 case with low expression, none of the metaplastic carcinomas expressed GHRH-R (P<0.005). A considerable number of TNBCs are positive for GHRH-R as a predictor of potential response to anti-GHRH-R treatment. This expression however, varies considerably between histologic subtypes of triple-negative breast cancers. Although most medullary and metaplastic carcinomas do not express GHRH-R, three fourths of the IDC-NST show a positive reaction. Testing for GHRH-R expression is therefore advisable if anti-GHRH-R therapy is being considered.