The Significance Of The TGF-β, TGF-βⅡ Receptor And Smad4 Protein Expression In Human Colorectal Cancer

[Background]: Colorectal cancer is a malignant tumor originated from epithelium of colorectal mucosa, whose morbidity is increasing and is almost next to gastric cancer and esophageal cancer in gastrointestinal cancer. The 5-year overall survival of the patients with obvious symptom is thirty two percent statistically. Thus, the research of the pathogenesis and prognostic prediction in colorectal cancer has become one of the hotspots.The carcinogenesis and progression of colorectal cancer is a multi-gene and multi-step course. Chromosome instability and microsatellite instability are two main pathways to affect colorectal cancer progression.Chromosome instability mainly includes the mutation of APC, P53 and DCC/Smad4. Thus, changing signal transduction pathways such as TGF-β could have an effect on the carcinogenesis and progression of malignant tumors. Smad/DPC4 is a tumor suppressor gene discovered recently. Some studies indicated that Smad/DPC4 played an important role mainly in colorectal cancer, breast cancer and gastric cancer.[Objective] To detect the expression of Smad4 protein, TGF- β and TGF- β II R protein in human colorectal cancer and analyze the relationship between these protein's expression and clinical characteristics including pathological and prognostic factors.[Methods] Total 76 patients pathological diagnosed with colorectal cancer by surgery in The Zhejiang Cancer Hospital from December 1998 to November 2000 were collected and the expression of Smad4 protein, TGF- β and TGF- β II R protein were measured in both specimens of normal mucosa and tumor tissue with immunohistochemistry (IHC). The relationship between the expression of Smad4 protein, TGF- β and TGF-β II R protein and the clinic-pathological factorswas analyzed and all patients were followed up to July 2006.[Resluts] 1. The positive rate of Smad4 protein expression in the tumor tissues and normal mucosa were 35.5% (27/76) and 63.2% (48/76) respectively and their difference is significant statistically (P<0.01). 2. The positive rate of TGF- β protein in tumor tissue and normal mucosa were 25.0% (19/76) and 42.1% (32/76) respectively and their difference is significant statistically too (P<0.05). 3. The positive rate of TGF-β II R protein in tumor and normal mucosa were 18.4% (14/76) and 21.1% (16/76) respectively. There is no significant difference statistically (P>0.05); 4. The high level expression of Smad4 protein in tumor tissue was relative to the earlier tumor stage and fewer lymph node metastasis (P<0.05) . 5. There is no relationship between Smad4 protein and gender, age, tumor location, tumor size, differentiation, tumor embolus, pathologic type, as well as TGF-β II R, TGF-β protein (P>0.05). 6. There is no significant difference between Smad4 protein and TGF-β , TGF- β II R protein (P>0.05). 7. There is significant difference between Smad4 protein and the 5-year overallsurvival(P<0.05); 8. There is no significant difference between TGF- β ,TGF- β II R protein and the 5-years overall survival (P>0.05) .[Conclusion] 1. Smad4 protein isdown-expressed in tumor tissue in contrast to normal mucosa in colorectal cancer patients and those patients with Smad4 protein lower expression are always accompanied with later stage, more lymph node metastasis and worse prognosis. Smad4 could be a useful prognostic marker in clinic. 2. TGF-β protein is down-expressed in tumor tissue in contrast to normal mucosa in colorectal cancer patients, but there is no significant difference between TGF-β expression and tumor stage, lymph node metastasis. 3. There is no significant difference of TGF-β II R protein expressed in tumor tissue and normal mucosa.