Abstract
Hypothalamic growth hormone (GH)-releasing hormone (GHRH) regulates the release of GH from the pituitary gland. The receptors for GHRH (GHRH-R) are expressed predominantly in the pituitary. Recent evidence demonstrates that splice variants of the GHRH receptor are also expressed in several nonpituitary tissues, both normal and tumoral, as well as in cancer cell lines. The aim of this study was to investigate the expression of the splice variant 1 (SV-1) of GHRH-R in colorectal cancer (CRC). Seventy patients who underwent partial colectomy for CRC were enrolled in the study. Immunohistochemical expression of SV-1 was studied in paraffin-embedded sections of patient tumor tissue. A cytoplasmic supranuclear expression of SV-1 was observed in CRC as well as in the normal colon mucosa. Tumor grade and pathological stage were negatively correlated with expression of SV-1 (P = 0.012 and P = 0.013, respectively). CRCs metastatic to the liver showed a lower expression of SV-1 than did primary tumors, but this difference was not statistically significant. Kaplan-Meier and Cox univariate survival analyses indicated an improved survival time in patients with high SV-1 compared with those with low GHRH-R expression, but this difference was not statistically significant. The immunohistochemical expression of SV-1 seems to be a favorable prognostic factor in CRC.
Highlights
Colorectal cancer (CRC) is globally the third most common malignancy among adults, and the fourth leading cause of cancer-related deaths after lung cancer [1,2]
Our results suggest that GHRH-R expression is a favorable prognostic factor in colorectal cancer (CRC), we were unable to analyze the association of progression-free survival with splice variant 1 (SV-1) immunohistochemical expression
One-third of patients who undergo a surgical resection with curative intent develop recurrent disease, and many CRCs are detected at a late stage when surgery cannot cure the disease
Summary
Colorectal cancer (CRC) is globally the third most common malignancy among adults, and the fourth leading cause of cancer-related deaths after lung cancer [1,2]. Recent studies indicate the involvement of growth factors in the tumorigenesis of various human tumors, including breast, uterine, endometrium, ovary, prostate, and lung as well as gastroenteropancreatic cancers [2,3,4]. Growth hormone (GH)-releasing hormone (GHRH) is a 40–44 amino acid hypothalamic peptide that regulates the secretion of GH from the anterior pituitary gland [5]. In addition to having neuroendocrine action, GHRH acts directly on a variety of peripheral tissues and tumors and induces cell proliferation [6]. These effects of GHRH and its antagonists are mediated in many tumors by a splice variant of GHRH-re-. Submitted March 31, 2009; Accepted for publication April 14, 2009; Epub (www.molmed.org) ahead of print April 15, 2009
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