INSERM, UMR1037 Cancer Research Center of Toulouse (CRCT), Université Paul Sabatier Toulouse III, 1 Avenue Jean Poulhés, BP 84225, 31432 Toulouse Cedex 4, Toulouse, France.
Cancer Prev Res (Phila). 2012 Apr;5(4):675-84. doi: 10.1158/1940-6207.CAPR-11-0408. Epub 2012 Feb 24.
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.
结肠中最常见的病变是增生性息肉。长期以来,增生性息肉被认为是没有恶性潜能的病变,不建议对这些患者进行结肠镜检查。然而,最近的研究表明,增生性息肉可能是某些散发性结直肠癌的前体病变。到目前为止,还没有生物标志物可以识别出具有恶性潜能的增生性息肉亚群。由于激素前体胃泌素已被涉及结肠癌变,我们研究了增生性息肉中胃泌素的表达是否可以预测增生性息肉切除后结肠肿瘤的发生。我们回顾性分析了 74 例无结直肠病史患者的增生性息肉中胃泌素的表达。在我们的研究中,41%的患者最初表现为增生性息肉,随后发展为腺瘤性息肉,被认为是结直肠腺癌的前体病变。在 40%的患者中,增生性息肉中胃泌素过度表达。我们发现胃泌素过度表达与无肿瘤生存时间缩短之间存在显著相关性(P=0.001)。胃泌素高表达的患者 5 年无肿瘤生存率为 38%,而胃泌素低表达的患者为 100%。此外,我们还基于胃泌素染色和患者年龄建立了一个预测试验,该试验预测首次出现增生性息肉后发生肿瘤的发生率,其敏感性为 100%(95%置信区间,79%-100%),特异性为 74%(51%-90%)。我们表明,增生性息肉中胃泌素表达的评估是一种有效的预后工具,可以确定具有更高发生异时性肿瘤风险的患者,这些患者可能受益于适应性随访。