| Colorectal carcinoma is one of the common malignant carcinoma that severely harms the public health. In western countries, the mortality of colorectal carcinoma has ranked second among all malignant carcinoma, next only to lung cancer. In China, the mortality is also increasing, currently ranking between the 4th to the 6th. With the advance of the comprehensive treatment plans, mainly involving surgical removals, there has been great progress in the prognosis in the colorectal carcinoma recently. However, the five-year survival rate is still only 60-70%. Although a perfect prognostic evaluation system can be used for guiding clinical treatments and reducing healthcare cost, traditional TNM grading system is still used in the majority of prognostic analysis. Recently, there has been great development in the scientific understanding of the colorectal carcinoma, especially the emergence of many bio-molecular markers. We believe building a prognostic evaluation system based on individual characteristics and bio-molecular markers is an urgent task.Based on the XIAOSHAN population cancer registry system, survival rates were calculated with life-table and the COX proportional hazards regression model were used to explore the independent effect of potential factor on prognosis. The tendency of location, age at diagnosis were analyzed with rank sum test.Surgical and pathological verified colorectal carcinoma cases were taken from the Xiaoshan tumor registry system during 1991-2000. All clinical and pathological data were individually reviewed. Those died within one month from surgery or died due to causes other than colorectal carcinoma were excluded from the study. Among the total of 320 cases, there were 101 colon carcinoma cases and 219 rectal carcinoma cases.183 of them were males and 137 were females. There were 226 cases undergone surgical treatments, including 155 colon carcinoma cases and 71 rectal carcinoma cases.124 of them were males and 102 were females.The survival data was provided by the Xiaoshan Center for Disease Control. All follow-up ended on Dec.31,2002. The duration of follow-up varied from 1 month to a maximum of 152 months, with the medium of 45 months and the mean of 52 months. The archival block of representative tumor tissues and corresponding normal tissues were sliced for HE staining and Envision immunohistochemical staining.Statistical analysis was performed using SPSS10.0 for Windows. Cumulative survival rate was calculated using life-table methods with a one-year step size. Survival curve was drawn using the univariate survival analysis based on Kaplan-Meier methods (the significance level tested by Log-rank method). OR values were calculated by using the univariate survival analysis based on univariate COX proportional hazard model. The statistically significant prognostic factors identified by univariate analysis were then analyzed using multivariate Cox proportional hazard model. The x 2 analysis was used for the correlation analysis between two factors, and for calculating Spearman's correlation coefficients, a=0.05.The average incidence of colorectal cancer was 11.55/100000; the colorectal cancer cases accounting for 8.99% of the total tumors, and was the fourth rank between 1991 to 2000.Of 2450 colorectal patients, the median age at diagnosis was 65.3 years. The median age at diagnosis of colon cancer was significantly greater than that of rectum cancer. The median age of patients diagnosed between 2000.1-2005.12 was significantly greater than that of patients between 1990.1-1995.12 and 1996.1-2000.12.The proportion of colon cancer is higher in patients whose age at diagnosis below 60 years old and diagnosed after 1996. The survival rates in 1,3 and 5 year were 51.5%,45.6% and 43.4%, respectively. Location, age and periods at diagnosis were found to significant prognosis factors.First we performed survival analysis on all 320 colon-rectum cancer cases. The five-year cumulative survival rate (FYCSR) for colorectal carcinoma was found to be 62.10%, where the FYCSR for colon carcinoma (71.96%) was higher than the FYCSR for rectal carcinoma (58.18%).The results also showed that the cumulative survival rates decrease over one-year, three-year and five-year periods, with the steepest decrease for rectal carcinoma. There was relatively no change for colon carcinoma. Therefore the percentages of colon cases and rectal cases are important when comparing the FYCSR in research data. When there is more rectal carcinoma in the data, the FYCSR must be low. In addition, when calculating the FYCSR using survival table, there was large discrepancy in the results using one-year interval v.s. five-year interval. Therefore the cumulative survival rates between different research data should not be simply compared.Because the FYCSR for colon carcinoma and rectal carcinoma were different, in order to understand the difference in prognostic factors for colon and rectal cancer, we performed survival analysis on the 101 colon carcinoma cases and 219 rectal carcinoma cases.There was obvious difference in the prognostic factors for colon and rectal carcinoma, Smoking, lymph node metastasis and serum albumin concentration were the independent factors in the prognosis for colon carcinoma, while TNM stage, metastasis and surgical method were the independent factors for rectal carcinoma. The radical surgical rate of colon carcinoma was higher than that of rectal carcinoma, while the post,surgical recurrence rate was lower. The reason may be that the prognostic factor of colon carcinoma are more related to the systemic status, while the prognostic factors of rectal carcinoma are more related to the tumor states and surgical treatment. Based on analysis results, we suggest that the colon and rectal carcinoma should be treated differently in both clinical treatment and scientific research.In order to further understand the significance of clinical-pathology parameters and molecular biomarkers in the prognosis of colorectal carcinoma, we did more research on the 226 post-surgery cases out of the 320 cases. Based on the previous clinical-pathology parameters, we further studied the following factors:growth fashion, vessel invasion, perineural invasion, tumor budding, tumor-infiltrating lymphocytes, peritumoral-lymphocytic infiltration and Crohn's like reactivity. We also studied the p53, Ki67, Bcl2, CXCR4 using immunohistochemical method.The FYCSR for all post-surgery colorectal carcinoma cases was 67.42%, which was higher than the FYCSR of the general colorectal cases (62.10%). The FYCSR for post-surgery colon carcinoma (72.41%) was higher than that for rectal carcinoma(65.24%).Age, perineural invasion, lymph node metastasis, metastasis, urine glucose and positive rate of p53 were identified as the independent factors for prognosis of post-surgery colorectal carcinoma by multivariate COX proportional hazar model. Peritumoral-lymphocytic infiltration, tumor budding, TNM stage and urine glucose were identified as significant factors of post surgery rectal carcinoma by multiivariate COX proportional hazar model.The analysis on post-surgery colorectal carcinoma showed that there was no difference in the survival for the two age groups:< 40 and 40-60. The survival was not good only for the age group that were older than 60.We also proved that the tumor budding was one of the independent prognostic factors in surgically treated rectum cancers using multivariate analysis. Tumor budding was the one or a group of (<5) undifferentiated tumor cells in the front of tumor. They are identified easily. In order to further understand the significance of tumor budding in clinic, the correlations between tumor budding and other pathological parameters, and the significance of tumor budding in prognosis were specifically analyzed on for 167 cases of adenocarcinoma.The correlation analysis of tumor budding with other pathological parameters showed that there are significant correlations between tumor budding and location, histological grading, the depth of invasion, vessel invasion, perineural invasion, tumor-infiltrating lymphocytes, peritumoral-lymphocytic infiltration, Crohn's like reaction, lymph node metastasis. Survival analysis showed that tumor budding was an independent prognostic factor for colorectal adenocarcinom. Therefore tumor budding is an important factor in diagnosis for colorectal carcinoma.Based on results above, we drew the following conclusions:1,The colorectal cancer cases accounting for 8.99% of the total tumors, and was the fourth rank. The incidences of the large intestine cancer in both sexes were increased with ages, especially higher above 45 years old. The incidence of the large intestine cancer in males was higher than that in females. The incidences of the large intestine cancer in both sexes were increased year by year, and the female's increased much than the males' during 1991 to 2000.2,The pattern of colorectal cancer in the population changes obviously, especially significant tendencies increasing age at diagnosis, the proximal shift for location and improvement of prognosis.3,Smoking, lymph node metastasis and serum albumin concentration are independent prognostic factors for colon carcinoma; while TNM stage, metastasis and surgical method are independent prognostic factors for rectal carcinoma.4,Age, perineural invasion, lymph node metastasis, metastasis, urine glucose and positive rate of p53 are independent prognostic factors for post-surgery colorectal carcinoma. Peritumoral-lymphocytic infiltration, tumor budding, TNM stage and urine glucose are independent prognostic factor for post-surgery rectal carcinoma5,In post-surgery colorectal carcinoma,there was no difference in the survival for the two age groups:< 40 and 40-60. The survival was not good only for the age group that were older than 60.6,There are some correlation between p53 level and prognosis, while Ki67, Bcl2 and CXCR4 levels are irrelevant to prognosis.7,Tumor budding is an important clinical and pathological indicator.
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