Apoptosis index and apoptosis-related antigen expression in serrated adenoma of the colorectum: the saw-toothed structure may be related to inhibition of apoptosis.
ABSTRACT Serrated adenoma of the colorectum is a recently proposed entity characterized by a saw-toothed structure of hyperplastic polyp and cytologic atypia of tubular adenoma. To clarify the role of apoptosis in morphogenesis of serrated adenoma, we investigated apoptotic indices and expression of apoptosis-related antigens in the tumor cells. Thirty-eight serrated adenomas were examined by the nick-end DNA labeling method and immunostained for CD95 (Fas), bcl-2, bax, and p53. Thirty-seven hyperplastic polyps, 48 tubular adenomas, and 16 sections containing normal colonic mucosa were similarly examined for comparison. The apoptotic indices in the upper and middle zones of the crypts of serrated adenomas and hyperplastic polyps were lower than those of normal colon mucosa and tubular adenomas with statistically significant differences. The CD95 expression was diffusely observed throughout the epithelium of normal crypts and tubular adenomas, whereas it was reduced in serrated adenomas and hyperplastic polyps. The bcl-2 expression was confined to the basal crypts in the latter two lesions but was diffuse throughout the neoplastic epithelium in tubular adenomas. The bax expression was increased in serrated adenomas and tubular adenomas but was decreased in hyperplastic polyps. Overexpression of p53 protein was observed in 50% of serrated adenomas, none of hyperplastic polyps, and 14% of tubular adenomas. These findings suggest that inhibition of apoptosis is caused by reduced CD95 expression in serrated adenomas and hyperplastic polyps, which may induce the characteristic saw-toothed structure in these lesions. Based on the similarities and differences between serrated adenoma and hyperplastic polyp observed in the present study, a progression from the latter to the former lesion may be postulated.
SourceAvailable from: Ali Salajegheh[Show abstract] [Hide abstract]
ABSTRACT: B-Raf is one of the more commonly mutated proto-oncogenes implicated in the development of cancers. In this review, we consider the mechanisms and clinical impacts of B-Raf mutations in cancer and discuss the implications for the patient in melanoma, thyroid cancer and colorectal cancer, where B-Raf mutations are particularly common.Experimental and Molecular Pathology 10/2013; 95(3). DOI:10.1016/j.yexmp.2013.10.005 · 2.88 Impact Factor
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ABSTRACT: A crucial role for Aurora Kinase A (AURKA) gene has been demonstrated in the advanced steps of colorectal tumor progression. Little is known, however, about its role in the early phases of the adenoma-carcinoma sequence. Moreover, no data are currently available concerning Aurora Kinase A involvement in the serrated tumorigenesis.Human pathology 12/2014; DOI:10.1016/j.humpath.2014.11.016 · 2.81 Impact Factor
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ABSTRACT: Serrated carcinoma (SC) is a subtype of colorectal carcinoma (CRC). Recently, the WHO estimated that it accounts for 7.5-9.2% of all CRCs. The diagnostic criteria proposed by Finnish authors, have been confirmed by Spanish research. Various studies show that SC has a worse prognosis than conventional CRC carcinoma (CC). Histological features with prognostic significance have been identified in SC, including the immunohistochemical expression of proteins implicated in tumour-budding formation and DNA repair, the microsatellite instability (MSI) status and the occurrence of KRAS and BRAF mutation. In agreement with clinical evidence, we have shown histologically that SC, with a distinct pattern of proteins at the invasive front and oncogene mutations, has a worse prognosis than CC. Thus, an accurate diagnosis of SC is of clinical importance.07/2013; 46(3):162–171. DOI:10.1016/j.patol.2013.03.005