The Association Of Autonomic Nerve With The Clinicopathological Parameters Of Colorectal Cancer Patients

Background: Colorectal cancer is one of the most common gastrointestinal cancer in our country.Recent years,the incidence of colorectal cancer increased rapidly due to the tremendous changes in people's lifestyles.Furthermore,the effects of traditoinal treatments(such as operation,radiotherapy,chemotherapy)are not ideal.As the research developming,the role of the tumor microenvironment in tumor progression has received growing attention.The nervous system in Tumor microenvironment has gradually become a "hot spot" in recent years.Previous studies have described that perineural invasion(PNI)is associated with a poor prognosis in a variety of tumors such as prostate cancer,pancreatic cancer and head and neck tumors.Recently,researchers reported that some degree of neurogenesis occured in the tumor microenvironment and was associated with a poor prognosis.Previous studies did not retrospectively analyzed the sympathetic and parasympathetic nervous.since there is a huge difference between the two nerve function,it is difficult to detect the role of the autonomic nervous system in colorectal cancer.In this study,we investigated existence of the autonomic nervous by Immunohistochemistry and examined the potential association between the autonomic nervous system and different clinicopathological parameter,then analyzing the potential significance in colorectal cancer.Objective:1 To investigate the existence of the sympathetic and parasympathetic nervous in colorectal cancer.2 To analyze respectively the association of the sympathetic and parasympathetic nervous with clinicopathological parameters.3 To further explore the role of the sympathetic and parasympathetic nervous in colorectal cancer.Methods:1 This analysis is to reveal tumor-infiltrating sympathetic fibers [adrenergic,identified by tyrosine hydroxylase(TH)staining] and intratumor parasympathetic fibers [cholinergic,identified by vesicular acetylcholine transporter(VAChT)staining].By immunohistochemistry,we investigate the existence of the sympathetic and parasympathetic nervous in 52 patients.2 This reasearch is not only to examine the association between the autonomic nervous system and the various clinicopathological characteristics but also to evaluate the ralationship between the autonomic nervous system and survival.Results:1 Clinicopathological data60 patients were interviewed by telephone.The information of 52 patients were obtained.Follow-up rate was 86.7%.14 patients were died.The reason of death was tumor metastasis(7 patients lung metastasis,3 patients bone metastasis,4 patients multiple metastases).The overall survival rate was 73.08%.15 patients were colon cancer,37 patients were rectal cancer.27 patients were male and 25 patients were female,28 patients were ?60 years,24 patients were >60 years.9 patients stage?,20 patients stage?,23 patients stage ?.1 patients stage T1,10 patients T2,22 patients T3,19 patients T4.The patients Without lymph node metastasis were 29 cases,The patients With lymph node metastasis were 23 cases.The patients with platelet normal(100-300×10~9/L)were 30 cases,increased(>300×10~9/L)were 22 cases.The patients with CEA normal(1-5ng/ml)were 34 cases,increased(>5ng/ml)were 18 cases.The patients with sympathetic negative were 25 cases,positive were 27 cases.The patients with parasympathetic negative were 21 cases,positive were 31 cases.2 The location of the autonomic nervous system in the tumor microenvironmentThe patients with sympathetic negative were 25 cases,positive were 27 cases.The patients with parasympathetic negative were 21 cases,positive were 31 cases.Most of the sympathetic fibers were seen in the stroma adjacent to the cancer cells.Most of the parasympathetic fibers were seen in the stroma away from the cancer cells.Some of the parasympathetic fibers were surrounded the blood vessels and sporadically located among tertiary lymphoid tissue.3 The relationship between sympathetic nervous and clinical featuresThe presence of sympathetic nerve fibers is not associated with location,age,gender,stageT,stageTNM,the number of platelet and the level of CEA.Sympathetic nerve fibers were observed in only 34.78% of tumors with lymph node invasion whereas 65.52% of lymph node negative tumors contained nerve fibers(P=0.028).The prognosis of patients with sympathetic positive was better than patients with sympathetic negative(85.16%vs60.00%,P=0.041).4 The relationship between parasympathetic nervous and clinical featuresThe presence of parasympathetic nerve fibers is associated with age,stageT,stageTNM and the number of platelet.Parasympathetic nerve fibers were observed in only 39.29% of patients(?60 years)whereas 83.33% of patients(>60 years)(P=0.001).As the stage T advanced,the positive rate of parasympathetic nervous was gradually increased.(T1 0%,T2 30.00%,T3 59.09%,T4 78.95%,P =0.045).As the stage TNM advanced,the positive rate of parasympathetic nervous was gradually increased.(stage?11.11%,stage? 65.00%,stage? 73.91%,P =0.004).Parasympathetic nerve fibers were observed in only 46.67% of patients with platelet normal,as compared to 77.27% of patients with platelet increased(P=0.026).The prognosis of patients with parasympathetic negative was better than patients with parasympathetic positive(80.95%vs67.74%,P =0.323).Conclusions:1 Sympathetic and parasympathetic nerve fibers could infiltrate colorectal tumors.2 Sympathetic nerves stimulate early phases indicating good prognosis.Parasympathetic nerves activate the late metastatic process indicating bad prognosis and are associated with age,stageT,stageTNM and the number of platelet.