Abstract P4-06-07: Expression of growth hormone releasing hormone receptor ( GHRH-R ) in primary and metastatic mammary carcinomas

Abstract

Abstract In addition to its nominative function as a neurohormone acting on the pituitary, Growth Hormone Releasing Hormone (GHRH) has been shown to modify the growth behavior of numerous 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. As this work has been done predominantly on tumor cell lines and xenografts, we set out to examine the clinical analog. Matched primary and metachronous metastases from 50 breast cancers were included in this study of GHRH-R in breast cancer. Immunohistochemistry for GHRH-R (AbCam) was performed on paraffin sections and the staining results were assessed semi quantitatively from 0 (negative) to 3+ (strongly positive). A section from normal pituitary was used as positive control. Forty-three of the primary breast cancers (86%) that ultimately relapsed or metastasized showed moderate to strong immunohistochemical expression of GHRH-R. Tumors from the metastatic foci also showed strong immunoreactivity in 78%, 71%, and 44% of liver, brain, and bone foci, respectively. The lower intensity of staining in bone samples may be due to the effect of the decalcification process routinely performed before staining. Whenever present, the non-neoplastic glands adjacent to breast tumors showed either negative or 1+ reaction for GHRH-R. We conclude that the great majority of mammary carcinomas at primary and metastatic sites express GHRH-R. This finding could potentially serve as a basis for therapeutic approaches using peptide receptor antagonists. By receptor blockade using GHRH receptor antagonists, with minimal pharmacologic side-effects, we have been able to control the growth in a number of tumor cell lines (HCC1806, MDAMB468, MDAMB435S, MCF7, T47D, HCC1937, BT474, and MX1s). Based on the presence of GHRH receptors in these clinical tumors, we conclude that clinical trials evaluating GHRH receptor antagonists are indicated. Citation Format: Mehrad Nadji, Norman L Block, Andrew V Shally, Jonathan Lara, Rick Michaelson, Suhail M Ali, Kim Leitzel, Syed M Rizvi, Mhd Yaser Al-Marrawi, Allan Lipton. Expression of growth hormone releasing hormone receptor ( GHRH-R ) in primary and metastatic mammary carcinomas [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-06-07.