Ectopic production of prolactin by colorectal adenocarcinoma

Abstract

PURPOSE: This study assessed the role of prolactin in patients with Dukes B and C colorectal carcinoma.

METHODS: Circulating prolactin and carcinoembryonic antigen were assayed using immunoradiometric assay and radioimmunoassay kits, respectively, in preoperative blood (n = 98) and tumor-draining venous blood (n = 34) samples of colorectal carcinoma patients. Immunohistochemical localization of prolactin (n = 98), carcinoembryonic antigen (n = 98), and prolactin receptors (n = 56) was performed. The expression of prolactin messenger ribonucleic acid (n = 50) and prolactin receptor messenger ribonucleic acid (n = 50) was studied by reverse transcriptase polymerase chain reaction. Further, prolactin amplimer was sequenced.

RESULTS: Preoperative prolactin and carcinoembryonic antigen levels were significantly higher in patients with colorectal carcinoma than in controls (prolactin, P = 0.001; carcinoembryonic antigen, P = 0.0001). Univariate survival analysis showed that Dukes stage, histologic grade, and circulating prolactin were significant prognostic factors for determining overall survival (Dukes stage, P = 0.00001; histologic grade, P = 0.005; prolactin, P = 0.001). In multivariate analysis, besides Dukes stage, circulating prolactin emerged as the most significant independent prognostic factor influencing overall survival. Preoperative prolactin levels showed excellent significant correlation with response to therapy and progression of disease. A significant tenfold higher mean concentration of prolactin was observed in tumor-draining venous blood than in peripheral blood (P = 0.0001). Diffuse cytoplasmic staining for prolactin was seen in 51 percent (50/98) of the colorectal carcinomas. Prolactin messenger ribonucleic acid expression was seen in 88 percent (44/50) of the colorectal carcinomas. Sequence analysis of the 234-bp prolactin amplimer revealed that the sequence was homologous to exon 5 of pituitary prolactin messenger ribonucleic acid.

CONCLUSION: These multiple approaches confirmed that prolactin is produced by colorectal carcinoma cells. Looking at its prognostic value and correlation with disease activity, it may provide new insights into treatment for patients with colorectal carcinoma.

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