Molecular Pathology Screening Of Lynch Syndrome - Associated Colorectal

Objective:To screen the colorectal cancer relating to Lynch syndrome with immunohistochemistry staining, analyze the molecular pathological character of Lynch syndrome, evaluate the incidence of Lynch syndrome related colorectal cancer among the patients suffering from colorectal cancer hospitalized in Beijing area, summarize the feature of this disease in Beijing area, and provide suggestions for scientific, precise, and convenient screening and diagnosis.Material and methods:Eighty tumor tissue samples of patients suffering from colorectal cancer hospitalized in Beijing area were collected, and then applied with immunohistochemistry staining. The protein expression corresponding to MLH1, MSH2, MSH6 and PMS2 genes in the tumor tissue were observed under optical microscope with 100 times and 400 times. The results were judged according to the Friedrichs’standard for immunohistochemistry. The type and number of the mismatch repair genes with negative expression were took down. Evaluation of the nuclear staining reaction was performed in accordance with the immunoreactive score (IRS) proposed by Friedrichs et al:IRS= SI (staining intensity) x PP (percentage of positive cells). SI was determined as 0 is blue; 1, light yellow; 2, pale brown; and 3, brown. PP was defined as 0 is negative; 1, no more than 10% positive cells; 2, 11%～50% positive cells; 3,51%～80% positive cells; and 4, more than 80% positive cells. Ten visual fields from different areas of each tumor under 400-time optical microscope were used for the IRS evaluation. Tumor slices scoring at least 2 points in our study were classified positive expression of proteins; 1 point, weak positive expression; 0, loss of expression. Both weak positive expression and loss of expression were considered as negative expression. Positive controls were the normal intestinal mucosa epitheliums and (or) lymphocytes with positive staining from every section. The section with least one mismatch repair protein expressing negatively was considered as Lynch syndrome related colorectal cancer.Results:After immunohistochemistry staining screening, in the eighty collected colorectal cancer tumor tissue samples,14 samples showed loss of expression for at least one mismatch repair protein, whose proportion was 17.5%. Among these 14 samples,6 samples showed loss of expression for MLH1 protein,2 samples showed loss of expression for MSH2 protein,4 samples showed loss of expression for MSH6 protein,10 samples showed loss of expression for PMS2 protein; 5 samples showed isolated loss of expression for PMS2 protein, 4 samples showed loss of expression for MLHl and PMS2 proteins,1 sample showed loss of expression for MLH1、MSH6 and PMS2 proteins. Lynch syndrome related colorectal cancer patients were primarily male, mostly older than 64; the cancer, the pathological types of which were basically adenocarcinoma, mostly involved colon, differentiated moderately, and predominately had no signs of metastasis.Conclusions:The incidence of Lynch syndrome related colorectal cancer among the hospitalized patients with colorectal cancer in Beijing area is higher than the worldwide annual incidence. And loss of expression of PMS2 is especially prominent, which may be resulted from the feature of incidence among the Beijing population.