A New Biomarker That Predicts Colonic Neoplasia Outcome in Patients with Hyperplastic Colonic Polyps

Abstract

The most frequently occurring lesions in the colon are the hyperplastic polyps. Hyperplastic polyps have long been considered as lesions with no malignant potential and colonoscopy for these patients is not recommended. However, recent works suggest that hyperplastic polyps may represent precursor lesions of some sporadic colorectal cancers. Until now, no biomarker allows to identify the subset of hyperplastic polyps that may have a malignant potential. Because the hormone precursor progastrin has been involved in colon carcinogenesis, we investigated whether its expression in hyperplastic polyps predicts the occurrence of colonic neoplasm after resection of hyperplastic polyps. We retrospectively analyzed progastrin expression in hyperplastic polyps from 74 patients without history of colorectal pathology. In our study, 41% of patients presenting an initial hyperplastic polyp subsequently developed adenomatous polyps, recognized as precursor lesions for colorectal adenocarcinomas. Progastrin was overexpressed in the hyperplastic polyps in 40% of the patients. We showed a significant association between progastrin overexpression and shortened neoplasm-free survival (P ¼ 0.001). Patients with high overexpression of progastrin had a 5-year neoplasm-free survival rate of 38% as compared with 100% for the patients with low progastrin expression. In addition, we established a predictive test on the basis of progastrin staining and patients' age that predicts occurrence of neoplasm after developing a first hyperplastic polyp with a sensitivity of 100% [95% confidence interval (CI), 79%-100%] and a specificity of 74% (51%-90%). We show that progastrin expression evaluation in hyperplastic polyps is an efficient prognostic tool to determine patients with higher risk of metachronous neoplasms who could benefit from an adapted follow-up. Cancer Prev Res; 5(4);

Autocrine Secretion of Progastrin Promotes the Survival and Self-Renewal of Colon Cancer Stem–like Cells

“…Similarly, secretion by tumor cells of factors that promote their own proliferation or CSC self-renewal has been reported in the case of IL4 (7) and TGFb (45), raising interest in these factors as potential therapeutic targets or prognostic biomarkers. Accordingly, in view of the reported role of CSCs during early stages of tumor initiation, the promotion of self-renewal identified here provides a potential rationale for the proposed role of progastrin overexpression as a risk marker of neoplastic transformation in patients with hyperplastic colonic polyps (46). Homeostatic equilibrium within heterogeneous tumor cell populations involves proliferation and cell death rates of CSCs and non-CSCs, as well as rates of phenotypic transitions between the CSC and non-CSC states (8,32,47).…”

Opportunistic screening for colorectal neoplasia in Singapore using faecal immunochemical occult blood test

“…However, recent studies suggest that hyperplastic polyps may represent precursor lesions of some sporadic colorectal cancers. (22) Therefore, hyperplastic polyps were also included as colorectal neoplasia, together with adenomas and cancers, in our study. There are several limitations to this study.…”

Progastrin: a potential predictive marker of liver metastasis in colorectal cancer

“…Immunohistochemical staining A primary antibody and immunohistochemical staining methodology previously shown to detect PG in human CRC specimens was used in this study [7]. PG expression was detected using anti-human PG rabbit polyclonal antibody (1137; [1]) at 1:1000 dilution.…”