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Expression of GHRH-R, a Potentially Targetable Biomarker, in Triple-negative Breast Cancer
Mahsa Khanlari1, Andrew V Schally1,2,3, Norman L Block1
1Department of Pathology, University of Miami Miller School of Medicine, Jackson Memorial Hospital and Sylvester Comprehensive Cancer Center.
Purpose:
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.
Materials And Methods:
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.
Results:
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).
Conclusions:
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.
Insights
Growth hormone-releasing hormone receptor (GHRH-R) is expressed in over half of triple-negative breast cancers (TNBCs), particularly invasive ductal carcinomas. This finding suggests GHRH-R expression may predict response to targeted therapies in TNBC patients.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Growth hormone-releasing hormone (GHRH) influences cancer growth, including breast cancer.
- GHRH acts via the GHRH receptor (GHRH-R) on tumor cells.
- GHRH-R expression can predict response to GHRH-R antagonist therapy.
Purpose of the Study:
- To investigate GHRH-R expression in triple-negative breast cancers (TNBC).
- To correlate GHRH-R expression with TNBC histologic subtypes.
Main Methods:
- 134 primary TNBC cases were classified into medullary, metaplastic, apocrine, and invasive ductal carcinoma of no special type (IDC-NST) subtypes.
- Immunohistochemistry was used to assess GHRH-R expression semiquantitatively.
- Staining results were correlated with histologic subtypes.
Main Results:
- GHRH-R was expressed in 77 (57%) of 134 TNBCs.
- Invasive ductal carcinomas of no special type (IDC-NST) showed the highest positive reaction rate (77.6%).
- Medullary and metaplastic carcinomas demonstrated minimal to no GHRH-R expression.
Conclusions:
- A significant proportion of TNBCs express GHRH-R, indicating potential for anti-GHRH-R treatment.
- GHRH-R expression varies significantly across TNBC histologic subtypes.
- Testing for GHRH-R is recommended for patients considered for anti-GHRH-R therapy.
