Results Expression of Savolitinib p-ERK1/2 and PI3-K in human gallbladder adenocarcinoma, peri-tumor tissues, adenomatous polyps, and chronic cholecystitis Immunohistochemistry for p-ERK1/2 and PI3-K were conducted with 108 gallbladder adenocarcinomas, 46 surrounding tissues of gallbladder adenocarcinoma, 15 adenoma polyps, and 35 chronic cholecystitis samples.
Positive staining for p-ERK1/2 was observed in the cytoplasm VX-689 supplier and/or nucleus (Figure 1 and 2a–c). PI3-K staining was mostly seen in the cytoplasm as expected (Figure 1 and 2d–f). As shown in Table 1, of the 108 gallbladder adenocarcinomas, expression of p-ERK1/2 and PI3-K was detected in 63 (58.3%) and 55 cases (50.9%), respectively. In the 46 surrounding tissues of gallbladder adenocarcinoma, p-ERK1/2 and PI3-K were positive in 14 (30.4%) and 5 (10.1%) cases, respectively. Moderate to severe atypical hyperplasia were observed in all gallbladder mucous epithelium in p-ERK1/2 positive cases. In PI3-K positive samples, however, gallbladder
mucous epithelium was normal in one case, mild atypical hyperplasia in one case, while moderate and severe atypical hyperplasia were seen in one and 2 cases, respectively. Positive staining for p-ERK1/2 and PI3-K was both observed in 3 out of 15 adenoma polyps which all showed moderate to severe atypical hyperplasia. In the chronic cholecystitis group, p-ERK1/2 and PI3-K staining was positive in 4 (11.4%) and Selleck AMN-107 3 (8.6%) of the 35 cases, respectively. Gallbladder mucous epithelium in positive specimens showed moderate to severe atypical hyperplasia. Overall, the frequency of samples positive for p-ERK1/2 and PI3-K in gallbladder adenocarcinomas was significantly
higher than that in surrounding tissues (χ2 pERK = 10.04, P < 0.01; χ2 PI3-K = 21.77, P < 0.01), in adenoma polyps (χ2 pERK = 7.78, P < 0.01; χ2 PI3-K = 5.06, P < 0.01), and in chronic cholecystitis (χ2 pERK = 23.35, P < 0.01; χ2 PI3-K = 19.67, P < 0.01). Figure 1 Expression of p-ERK1/2 and PI3-K (original magnification 200×). Expression of p-ERK1/2 in well-differentiated gallbladder adenocarcinoma (a), moderately-differentiated gallbladder adenocarcinoma (b), and poorly-differentiated gallbladder adenocarcinoma (c); PI3-K expression in well-differentiated (d), moderately-differentiated (e), and poorly-differentiated gallbladder adenocarcinoma (f). Figure 2 Immunohistochemical staining mafosfamide of p-ERK1/2 and PI3-K (original magnification 200×). p-ERK1/2 expression in peri-tumor tissues with severe atypical proliferation of gallbladder adenocarcinoma (a), in gallbladder adenoma polyps with moderate atypical proliferation (b), in chronic cholecystitis with moderate atypical proliferation (c). PI3-K staining in surrounding tissues with severe atypical proliferation of gallbladder adenocarcinoma (d), in gallbladder adenoma polyps with severe atypical proliferation pericancerous tissues (e), and in chronic cholecystitis with mild (f).