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 = 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.
Highlights
In the general population, the most frequently occurring lesion in the colon is the hyperplastic polyp, with a prevalence of 10% to 35% in Western populations [1]
No hyperplastic polyp displayed the major histologic features described for sessile serrated adenomas (SSA), including architectural abnormalities and loss of expression of MLH1 [4, 10, 33] The subset of patients with colonoscopic follow-up was representative of the whole cohort as no statistical difference on clinical and immunohistochemical features was found between patients with a colonoscopic follow-up and the ones with a medical follow-up
This supports the hypothesis that this hormonal precursor, known to be expressed in human colorectal adenomas and adenocarcinomas, could play a protumoral role at the very early stage of colonic carcinogenesis
Summary
The most frequently occurring lesion in the colon is the hyperplastic polyp, with a prevalence of 10% to 35% in Western populations [1]. Large hyperplastic polyps (size > 1 cm) and the presence of multiple hyperplastic polyps (number > 5) in hyperplastic polyposis syndrome have been clearly associated with colorectal adenomas or adenocarcinoma [2,3,4,5]. Other groups have proposed the idea that hyperplastic polyps may represent precursors of some sporadic colorectal cancers, in the serrated neoplasia pathway [7,8,9,10]. Despite these new data, the colonoscopy for patients with hyperplastic polyps is not recommended, except after resection of one large hyperplastic polyp (!1 cm) and/or multiple polyps The colonoscopy for patients with hyperplastic polyps is not recommended, except after resection of one large hyperplastic polyp (!1 cm) and/or multiple polyps (n ! 5) or if there is a family history of hyperplastic polyps, neither in the guidelines from the French National Agency for Accreditation and Evaluation in Healthcare, nor by the American College of Gastroenterology [11, 12]
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