Research On Expression Of HMLH1 And P53 In Sporadic Colorectal Carcinoma And Colorectal Adenoma

Objective To analyse the role of hMLH1 and p53 gene in the carcinogenesis ofsporadic colorectal carcinoma, we determined the expression of mismatch repair genehMLH1 and its relationship with p53 expression in sporadic colorectal carcinoma andcolorectal adenoma.Methods The expression of mismatch repair gene hMLH1 and p53 in 60 cases ofsporadic colorectal carcinoma,45 cases of colorectal adenoma and 26 cases of normalcolon mucosa were retrospectively analyzed using PV-6000 immunohistochemicalmethod.Results (1)Loss of hMLH1 expression were found in 18.3%(11cases,11/60) sporadiccolorectal carcinoma, 4.4%(2cases,2/45) colorectal adenoma and 0.0%(0case,0/26)normal colon mucosa respectively. There was a significant correlation between theobserved lost immunoexpression and some clinical and pathological characteristics, suchas age, tumor location, histological type and histological grade. There was a highly lossexpression rate of hMLH1 in＜40 years old, proximal-sided location, poorlydifferentiated carcinoma and mucous carcinoma (P＜0.05 or P＜0.01). There was nosignificant correlation between the loss of hMLH1 immunoexpression and patient'sgender, tumor gross type, tumor size, invasive depth, lymph node metastasis, distantmetastasis and Dukes stage(P＞0.05). (2) Positive expression of p53 protein were foundin 53.3%(32cases, 32/60) sporadic colorectal carcinoma, 20.0%(9cases, 9/45) colorectaladenoma and 0.0%(0case,0/26) normal colon mucosa respectively. The positiveexpression of p53 protein did not correlate with patient's gender, tumor gross type, tumorsize, invasive depth, lymph node metastasis, distant metastasis and Dukes stage(P＞0.05),but was closely related to patient's age, tumor location, histological type and histologicalgrade(P＜0.05). There was a highly positive expression rate of p53 protein in＞40 years old, distal-sided location, poorly differentiated carcinoma and mucous carcinoma(P＜0.05). The positive expression of p53 protein was closely related to adenma site,histological type and dysplasia grade. There was a highly positive expression rate of p53protein in distal-sided location, villi adenoma and high grade dysplasia(P＜0.05), but itdid not correlate with patient's gender and age(P＞0.05). (3)The positive expression ofp53 was lower in the group of hMLH1 negative expression than that in the group ofhMLH1 normal expression (P＜0.05).Condusion (1)The sporadic colorectal carcinoma were developed via differentpathway. Majority of sporadic colorectal carcinoma were developed via the chromosomalinstability pathway in which the p53 gene played more important role, meanwhile therewas a subset of sporadic colorectal carcinoma displaying MMR defective, with speciallyclinical and pathological features. (2) There was a subset of colorectal adenomadiaplaying MMR loss expression of hMLH1 protein and positive expression of p53protein. Defect of hMLH1 gene and mutation of p53 gene might occur in the early stageof carcinogenesis in sporadic colorectal carcinoma. (3) The expression of p53 wasnegatively correlated with the loss of hMLH1 expression.