Background Colorectal sessile serrated adenoma/polyps (SSA/Ps) are characterized by asymmetrical distribution of Ki67-positive cells, which varies among crypts and involves the crypt length to a ...variable extent; the pattern has been designated as aberration of crypt cell compartmentalization. The regenerating gene (REG) Ialpha is a cell growth and/or anti-apoptotic factor and its overexpression might be associated with aberration of crypt cell compartmentalization in SSA/Ps. We investigated REG Ialpha expression in SSA/Ps in comparison to hyperplastic polyps (HPs). Methods A total of 64 cases of serrated polyps (greater than or equai to10 mm in size), including 53 SSA/Ps and 11 HPs, were included in the present study. Immunostaining was performed using a labeled streptavidin-biotin method. REG Ialpha expression was classified as follows: (i) expression of endocrine cells: grade 0 (a few positive cells) to 3 (marked increase in positive cells); (ii) expression of goblet cells: grade 0 (negative) to 2 (positive for crypts and surface epithelial cells); (iii) staining intensity of goblet cells: grade 0 (negative) to 2 (strong); (iv) staining intensity of crypt (absorptive) cell membranes: grade 0 (negative) to 2 (strong). The presence of aberration of crypt cell compartmentalization was assessed using Ki67 immunostaining. Results With regard to the REG Ialpha expression of endocrine cells, 8 out of 11 HPs (73%) were grade 0, whereas 51 of 53 SSA/Ps (96%) were grade 1 or higher (p < 0.001). With regard to the distribution of REG Ialpha-immunoreactive goblet cells, 10 of 11 HPs (91%) were grade 1, whereas 50 of 53 SSA/Ps (94%) were grade 2 (p < 0.001). A similar trend was found in the staining intensity of goblet cells or crypt cell membranes (p = 0.011). Aberration of crypt cell compartmentalization was more frequently identified in SSA/Ps (72%) than in HPs (18%; p = 0.002). A significant association was observed between REG Ialpha overexpression and the aberration of crypt cell compartmentalization in serrated polyps (p = 0.037). Conclusions REG Ialpha overexpression is a characteristic of SSA/Ps, which appears to reflect aberration of crypt cell compartmentalization. Virtual slides The virtual slide(s) for this article can be found here: Keywords: Colon, Crypt cell compartmentalization, Hyperplastic polyp, REG Ialpha, Sessile serrated adenoma/polyp
Adenomatous areas are found frequently within or in the vicinity of carcinoma of the ampulla of Vater. This makes definite diagnosis difficult in the preoperative examination. The adenoma–carcinoma ...development hypothesis is generally accepted for colorectal tumors. Recently, a genetic alteration model during colorectal tumor development has attracted much attention, leading to various studies. We studied clinicopathologic features, prognostic factors, and the alteration of the p53 tumor suppressor gene using p53 immunohistochemical staining in pure adenomas, pure carcinomas, and carcinomas with adenomatous areas. A proliferative activity of the tumors using Ki-67 was also evaluated. Nine cases of pure adenoma and 198 cases of carcinoma of the ampulla of Vater were selected for this study. Among the 198 cases of the carcinoma, 83 cases (42%) had adenomatous areas. Positivity of p53 immunohistochemical staining was 0% in pure adenomas, 36% in the adenomatous areas of carcinomas with adenomatous areas and 62% in the carcinomatous areas of carcinomas with adenomatous areas, and 56% in pure carcinoma. Accumulation of p53 protein and the Ki-67 labeling index revealed no significant difference in prognosis. The clinicopathological factors examined were as follows: degree of invasion of the surrounding tissue, such as duodenal wall; pancreatic parenchyma; the presence or absence of lymphatic permeation; venous invasion; perineural invasion; the presence of regional lymph node metastasis; and TNM stage. Each of the clinicopathological factors showed a significant difference. Multivariate analysis revealed strong predictors for a worse prognosis: presence of lymphatic permeation, invasion of the pancreas, and perineural invasion. In conclusion, our results are consistent with the adenoma–carcinoma development hypothesis. It would seem that the molecular events leading to p53 accumulation in neoplasms of the ampulla of Vater occur relatively late during the oncogenetic process. Moreover, we think it may be useful to refer to the p53 overexpression in the diagnosis of ampullary tumors.
Aims : To evaluate the relationship between phenotypic expression and tumour progression as represented by macroscopic features, submucosal invasion and lymph node metastasis in early differentiated ...gastric adenocarcinoma.
Methods : One hundred and fifty‐five cases of early gastric differentiated adenocarcinoma without any poorly differentiated components were studied. The mucosal and submucosal components of carcinomas and lymph node metastatic lesions were classified into four categories, gastric type (G‐type), incomplete intestinal type (I‐type), complete intestinal type (C‐type) and unclassified type (U‐type), based on the combination of the phenotypic expression of HGM (gastric foveolar epithelium), MUC6 (gastric pyloric glands), MUC2 (intestinal goblet cells) and CD10 (small intestinal brush border). In addition, a new classification representing a phenotypic shift from mucosa to submucosa or from primary lesion to lymph node metastasis was established with the categories of preserved group (P‐group), loss group (L‐group) and acquired group (A‐group).
Results : (1) In submucosal carcinoma, U‐type was more common in the submucosa (39%) than in the mucosa (9%). (2) U‐type was more common in the metastatic lesions (42%) than in the primary lesions (5%). (3) The submucosal component and lymph node metastatic lesions were classified as P‐group in 48% and 43% of cases, respectively, and as L‐group in 50% and 52% of cases, respectively. (4) Lymph node metastatic lesions comprising undifferentiated carcinoma were classified as L‐group in 100% of cases.
Conclusion : During the course of tumour progression, early differentiated adenocarcinoma at first tends to lose its phenotypic expression despite preserving its morphology, but subsequently morphological dedifferentiation occurs.
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