Molecular Markers in Mucosa Harboring Gastric Adenomas

Abstract

Gastric adenoma (non-invasive low-grade and high-grade intraepithelial neoplasia) has been considered as one of the important precursor lesions in gastric carcinogenesis. Genetic events leading to the development of adenoma are not completely understood. Aim: To classify the histologic type of the adenomas according to mucin phenotype and to evaluate the gastric mucosa harboring adenomas for molecular markers. Methods: 40 gastric specimens were retrospectively collected from 20 patients who underwent surgical or endoscopical mucosal resection. The tissues were examined by immunohistochemistry for p53, p16ink4a, Bcl-2, cyclin D, and Ki-67. MUC2 (goblet cell mucin) and MUC5AC (gastric-foveolar mucin) were utilized to classify the gastric adenomas in intestinal or gastric type. Results: 12 (60%) patients were men. The mean age was 67.9 ± 12.9 years old. Intestinal type adenomas were detected in 13 (65%) patients and gastric type in 7 (35%) cases, according to the type of mucin. The adenomas were classified as non-invasive low-grade intraepithelial neoplasia (low-grade adenoma) in 13 cases (65%), and high-grade in 3 (15%). Intramucosal carcinoma within the adenoma was detected in 4 (20%) patients. Six (30%) patients had also separated adenocarcinoma distant to the adenoma. 10/13 of the low-grade adenomas and 3/3 high-grade adenomas were of intestinal type; 4/6 separated tumors were of intestinal type, while 4/4 adenomas with adenocarcinoma foci were of gastric type, p = 0.02. p53 immunoexpression was observed in 6/20 (30%) of adenomas, and in 2/6 (33.3%) of separated tumors. There was an association between p53 immunoexpression and intestinal type of adenoma, p = 0.031. Cytoplasmic and nuclear p16 immunoexpression was observed in 15 (75%) of the adenomas and in 62.5% of the tumors. Strong Bcl-2 immunoexpression was shown in 17 (85%) of the adenomas and in 4/6 (66.6%) of the separated tumors. Cyclin D was immunoexpressed in 16 (80%) of the adenomas and in 50% of the tumors. Ki-67 labeled index was not associated to the grade of adenoma or histologic type of adenocarcinoma, nonetheless it was statistically higher in carcinomas than in adenomas. Conclusions: 1. Mucin phenotype may be used to differentiate the histologic type of gastric adenomas and may guide the appropriate treatment; 2. p53 immunoexpression is associated to intestinal type of adenoma/tumor, indicating the same route of carcinogenesis. Gastric adenoma (non-invasive low-grade and high-grade intraepithelial neoplasia) has been considered as one of the important precursor lesions in gastric carcinogenesis. Genetic events leading to the development of adenoma are not completely understood. Aim: To classify the histologic type of the adenomas according to mucin phenotype and to evaluate the gastric mucosa harboring adenomas for molecular markers. Methods: 40 gastric specimens were retrospectively collected from 20 patients who underwent surgical or endoscopical mucosal resection. The tissues were examined by immunohistochemistry for p53, p16ink4a, Bcl-2, cyclin D, and Ki-67. MUC2 (goblet cell mucin) and MUC5AC (gastric-foveolar mucin) were utilized to classify the gastric adenomas in intestinal or gastric type. Results: 12 (60%) patients were men. The mean age was 67.9 ± 12.9 years old. Intestinal type adenomas were detected in 13 (65%) patients and gastric type in 7 (35%) cases, according to the type of mucin. The adenomas were classified as non-invasive low-grade intraepithelial neoplasia (low-grade adenoma) in 13 cases (65%), and high-grade in 3 (15%). Intramucosal carcinoma within the adenoma was detected in 4 (20%) patients. Six (30%) patients had also separated adenocarcinoma distant to the adenoma. 10/13 of the low-grade adenomas and 3/3 high-grade adenomas were of intestinal type; 4/6 separated tumors were of intestinal type, while 4/4 adenomas with adenocarcinoma foci were of gastric type, p = 0.02. p53 immunoexpression was observed in 6/20 (30%) of adenomas, and in 2/6 (33.3%) of separated tumors. There was an association between p53 immunoexpression and intestinal type of adenoma, p = 0.031. Cytoplasmic and nuclear p16 immunoexpression was observed in 15 (75%) of the adenomas and in 62.5% of the tumors. Strong Bcl-2 immunoexpression was shown in 17 (85%) of the adenomas and in 4/6 (66.6%) of the separated tumors. Cyclin D was immunoexpressed in 16 (80%) of the adenomas and in 50% of the tumors. Ki-67 labeled index was not associated to the grade of adenoma or histologic type of adenocarcinoma, nonetheless it was statistically higher in carcinomas than in adenomas. Conclusions: 1. Mucin phenotype may be used to differentiate the histologic type of gastric adenomas and may guide the appropriate treatment; 2. p53 immunoexpression is associated to intestinal type of adenoma/tumor, indicating the same route of carcinogenesis.