Gastrin-Releasing Peptide Receptor Expression in Cervical Cancer

Abstract

Objectives: It was the aim of this study to evaluate whether cervical neoplasms and adjacent tissues express the gastrin-releasing peptide receptor (GRPR) and whether there is a significant difference in its distribution among preinvasive and invasive cancers. Methods: Sections of paraffin-embedded cervical tumors (n = 88) and non-neoplastic control cervical tissues (n = 14) obtained from women registered in the Pathology Department, Academic Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Brazil, were investigated by immunohistochemistry for GRPR. Results: GRPR was detected in 99% of tumor specimens, mostly exhibiting a diffuse strong staining. The receptors were seldom detected in the endocervices, while ectocervices expressed GRPRs only when adjacent to neoplastic lesions. No correlation between GRPR expression and preinvasive and invasive neoplasms was found. Conclusions: To the best of our knowledge, this is the first demonstration of the widespread GRPR expression in human cervical cancer. The presence of receptors both in tumors and surrounding tissues may suggest that GRPR can play a role in the cervical carcinogenic process. These data provide a molecular basis for exploiting GRPR as a target for diagnostic and therapeutic purposes in cervical neoplasms.

BDNF/TrkB Content and Interaction with Gastrin-Releasing Peptide Receptor Blockade in Colorectal Cancer

“…Expression of TrkB and GRPR in HT-29 and SW620 cells and colorectal tumor samples was analyzed with immunohistochemistry following the general methods described in previous studies [20,21]. The primary antibodies used were a rabbit polyclonal antibody against GRPR (OPA1-15619; Affinity Bioreagents, Golden, Colo., USA), corresponding to the second extracellular loop of human GRPR, and a mouse monoclonal antibody raised against an extracellular domain of the human TrkB receptor (ab51190; Abcam plc, Cambrigde, UK), corresponding to the portion near the site of phosphorylation of tyrosine 515.…”

“…The primary antibody diluted in solution (1:50) was incubated for 12 h at 4°C, followed by application of the complex biotin streptavidin-biotin-peroxidase (LSAB; Dako) and revelation with diaminobenzidine tetrahydrochloride (DAB Kit, Dako). Cell nuclei were lightly counterstained with HE as a control [20,21]. …”

The Gastrin-Releasing Peptide Receptor as a Marker of Dysplastic Alterations in Cervical Epithelial Cells

“…In an earlier immunohistochemical study, we found aberrant GRPR expression in dysplastic squamous lesions and invasive squamous carcinomas of the cervix, in contrast to low expression in normal epithelia and endocervices. Based on those findings, we postulated that GRPR could be involved in cervical carcinogenesis [13]. These results prompted us to continue investigating GRPR immunosignaling in cervical smears.…”

“…For p16 expression, we used a p16-INK4A-specific monoclonal antibody, clone E6H4 (Dako AS, Glostrup, Denmark), primary antibody. The immunohistochemical methods have been described in our previous study [13]. Briefly, after dewaxing, inactivating endogenous peroxidase activity and blocking cross-reactions with normal serum, 4-µm sections were incubated overnight at 4°C with a diluted solution of the primary antibody (1:50).…”

“…In addition, we have recently described the aberrant expression of GRPR in both cervical dysplasias and invasive carcinomas. Based on the presence of this receptor in 99% of the evaluated samples, but not in nonmalignant cervices, it has been suggested that GRPR may play a role in cervical carcinogenesis [13]. These data provided the molecular basis for exploiting GRPR as a target for cervical cancer diagnosis.…”