Analysis Of Difference Between Colon Cancer And Rectal Cancer In Clinical Features, Molecular Mechanism Of Oncogenesis

Background:Colorectal cancer is one of most common cancer in gastrointestinal tract, and the morbidity is gradually increased in China recently years. According to the epidemiological data, the distinguished difference between colon and rectal cancer in morbility model and etiology was existed. Rectal cancer is more common in China, Compared with 80's years, the percentage of rectal cancer is decreased within 10 years, this changing illustrated that onset of colon cancer is more associated with life style and west-habit of diets than rectal cancer. In the meantime, because of difference site of cancer, the clinical manisfastation, laboratory examination and treatment method were different, the difference mechanism must existed in cancer development. The carcinogenesis of colorectal cancer is clear right now, the typical is "normal—adenoma polyps—cancer, and also called chromosomal instability pathway, in which Wnt signal, many oncogenes and anti-oncogenes were involved. Another important pathway is microsatellite instability (MSI), in which several mis-match repared(MMR) gene were mutant. Right now many study confused colon cancer and rectal cancer and put them together. Whether the mechanism is similar or difference between these two tumors is not clear. Several paper reported that APC, p53 and K-ras mutation were higher in colon cancer than rectal cancer, and MSI also common in colon cancer. But further and systemic study should be done to confirm.Objective:In-patient colon cancer and rectal cancer in recent 10 years were summarize for analysis the changing of morbidity and the difference of clinical features. Tissue samples of colon cancer and rectal were collected for immunohistochemistry and gene microarray detection, in order to investigate the difference the oncogenesis mechanism, which focus on the important factors in chromosomal instability pathway and MIS. This study will provide the information for early diagnosis, screening and prevention according different tumor site.Methods and materials:1906 cases of in-patient colon cancer and rectal cancer in Peking Union Medical College Hospital from 1999-2008 were summarize and morbidity changing, clinical manifestation, laboratory examination, diagnosis methods, and pathological stage were analysis retrospective. Each 30 cases of colon and rectal cancer operated tissue sample were detected by immnohistochemistry for APC,Wnt1,β-catenin,p53,MLH1,PMS2,MSH2,MSH6 protein expression. Microdissection and PCR-sequecing were used to detect the mutation of K-ras in the specimens. Gene profile were analysis using microarray technique in 16 colorectal cancer sample for probe the difference of gene expression in colon and rectal cancer.Results:The clinical data shown that the mobidity of colorectal was increased in recently 10 years(1.39% vs 0.97% p<0.05),More patients were rectal cancer aging between 40～60 and colon cancer aging over 70 years old (p<0.05).Hematochezia and changing of bowel habit were occurred in rectal cancer, which is 76.9% vs 31.7% and 71.9% vs 33.9%(p<0.01) respectively. Compared with rectal cancer, abnormal of stool routine was less and Hb decreased was more often significant in colon cancer (p<0.01). Less patients performed CEA test and abnormal was not common in rectal cancer (57.9% vs 31.1% p＜0.01).High positive rate(87.9%) of rectal touch was in rectal cancer, and colonoscopy was the mainly diagnosis method in colon cancer and polyps were found (35.7% vs 19.7% p<0.01). Operation was the mainly treatment in both patients. Immunohistochemistry detection shown that APC protein absent, wnt1 and p53 positive was higher in rectal cancer (46.7% vs 40.0%,66.7% vs 50.0% 86.7% vs 76.7%), but there was no significant difference.β-catenin positive above 90% in both tumor. MLH1,PMS2,MSH2,MSH6 absent were common in colon cancer (8 cases 26.7%) and rectal cancer only 4 cases (13.3% p＜0.01).In colon cancer, MLH1 and PMS2 disappeared at same time and account 87.5%,and MSH2 and MSH6 together absent in 100% of rectal cancer. K-ras mutant was detected in 53.3% colon cancer and 36.6% rectal cancer (p<0.05). The data of gene expression microarray analysis show that between colon and rectal cancer, the significant different was found in many genes expression.Conclusion:Morbidity of colon cancer and rectal cancer were increased. The clinical manifestation was less specific in colon cancer. In clinic, if the symptom occurred in high risk patients, physical examination and endoscopy should be combined in order to early diagnosis. In carcinogenesis, the wnt signal was exist in both tumor, but the activated factor maybe difference. MSI was common in colon cancer and MLH1 and PMS2 were involved. In short, between colon cancer and rectal cancer, common factors and different features were existed in the meantime.