The Immunohistochemical Expression of Growth Hormone-Releasing Hormone Receptor Splice Variant 1 Is a Favorable Prognostic Marker in Colorectal Cancer

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.

Ferulic Acid Exerts Anti-Angiogenic and Anti-Tumor Activity by Targeting Fibroblast Growth Factor Receptor 1-Mediated Angiogenesis

“…After euthanizing mice on Day 25, deparaffinized tumor sections were stained with specific antibodies, including CD31 (Abbiotec, Stockholm, Sweden), p-FGFR1 Y154 , p-PI3K p85 Tyr458 and p-Akt Thr308 . Detection was done with avidin-biotin-HRP complex (Thermo Scientific, Hudson, NH, USA) and diaminobenzidine as the chromogen [ 37 ]. Nuclei were counterstained with hematoxylin.…”

Immunohistochemical expression of somatostatin receptor subtypes 2 and 5 in colorectal cancer

“…Each immunohistochemistry slide was evaluated independently by two blinded, trained pathologists (IE and CP) using intermediate power light microscopy [21]. One representative tumour section was stained and evaluated per case.…”

“…Immunohistochemical expression of Sst2 and Sst5 was predominantly cytoplasmic and was categorized as either grade 1 (weak intensity), grade 2 (moderate intensity) or grade 3 (strong intensity). The H scoring system, a model that incorporates both intensity and distribution of staining [21,22], was used for semiquantitative analysis of Sst immunoreactivity. More specifically, the percentage of positive tumour cells was measured in every section and multiplied by 1, 2 and 3, respectively (grade 1 score = % per cent grade 1 expression × 1; grade 2 score = % per cent grade 2 expression × 2; grade 3 score = % per cent grade 3 expression × 3).…”

Growth hormone-releasing hormone: Extrapituitary effects in physiology and pathology

“…90,92,93 These species are involved in the generation of various diseases related line 38 and colorectal cancer. 39 These findings suggest that GHRH may also be involved in the pathogenesis and growth of cancers.…”

“…9,41 This receptor has also been shown to possess a strong ligand independent activity. 9,23,42,43 Molecular and cellular biology techniques revealed the expression of SVs in several cancers, including prostatic, 23,30,31,[44][45][46] colorectal, gastric, pancreatic 37,39,47 and renal cancers, 48 lung cancers, 23,45,49 breast carcinomas, 23,29,[50][51][52] ovarian and endometrial carcinomas, 20,21,52,53 bone sarcomas, 37 glioblastomas 26,36,52,54,55 non Hodgkin's lymphomas, 56 SW 13 human adrenal carcinoma cell line, 38 primary human melanomas 57 and transformed mucosa of the oesophagus. 47 Our laboratory has also investigated whether human cancers express the pituitary type GHRH receptor.…”