Sex Hormone Receptors, And Vegf, Egfr And Cox-2 In Colorectal Liver Metastases

BACKGROUND: Colorectal cancer is a common gastrointestinal cancer and the incidence was increasing in China now. Liver is the most common metastatic site of colorectal cancer and the main reason of death from colorectal cancer. Epidemiological investigation showed that the incidence of colorectal cancer in women are lower than that in men(1.9:1). The risk of sufferring colon cancer in postmenopausal women is higher than in premenopausal women. Application of estrogen replacement therapy in postmenopausal women can reduce the risk of colon cancer by 30% ~ 40%. It has been found that sex steroid hormones regulated cell differentiation in intestinal mucosa and mature, and estrogen receptor and progesterone receptor express in normal colorectal tissue and tumor tissue. All of these indicate estrogen and progesterone affect these tumors'occurrence and development. In addition, estrogen (alone or combination with progesterone) replacement therapy in the clinical treatment of colorectal cancer have achieved a certain effect. It can be Speculated that CRC LM may associated with the level of sex hormones.OBJECTIVE: Study the expression of estrogen receptorα, estrogen receptorβ, androgen receptor, progesterone receptor in colorectal cancer tissues, normal tissues adjacent to cancer and liver metastasis tissues, discuss the roles play in colorectal cancer.Materials and Methods:Selection criteria: No pre-operative radiotherapy, chemotherapy. No taking hormone drugs within 1 year;Excluding criteria: lesions'size were too small to fit pathological examination and experimental studies. 43 cases of CRC with liver metastases and no metastasis in other organs from March 2000 to December 2008 were collorected as the experiment group, 43 cases of CRC with no metastases were colorected randomly at the same time as the control group, immunohistochemical SP method and the determination SuperPicTure TM Polymer two-step were used in the primary lesion of colorectal cancer, adjacent normal mucosa and estrogen receptor of liver metastasis (ERα, ERβ), progesterone receptor (PR ), androgen receptor (AR) expression. Statistical methods: The data were analyzed use a two-sample comparison, the fourfold table Fisher exact test,χ2 diverse segmentation method was used to calculate each two rates of varied rates, and t test comparing was used for two relatively small samples, the standard of admission testα= 0.05, by SPSS13.0 for statistical work has been completed windows package. The dates were analyzed using statistical software SPSS version13.0.RESULTS:No expression of ERαprotein were detected in colorectal lesions, normal mucosa and liver lesions. ERβprotein expression in liver lesions were 13.2% (5 / 43), less than in colorectal lesions 36.0% (31 / 86), the difference was statistically significant (P <0.05), and the rate of ERβprotein expression in normal mucosa was 60.5% (26/43, liver metastasis group), the difference was statistically significant (P <0.05). ERβprotein expression in colorectal cancer lesions between experimental and control group were 34.9%(15/43), 39.5%(17/43), the difference was not significant (P> 0.05), and in normal lesion were 60.5%(16/43), 62.8 %(27/43), the difference was not significant (P> 0.05). However, it was significant differencer between colorectal cancer and normal mucosa (P <0.05). PR protein expression in liver lesions were 4.7% (2 / 43), less than in colorectal lesions 40.7% (35/86), the difference was statistically significant (P <0.05), and the rate of PR protein expression in normal mucosa was 55.8% (24/43, liver metastasis group), the difference was statistically significant (P<0.05). PR protein expression in colorectal cancer lesions between experimental and control group were 39.5% (17/43), 41.9% (18/43), the difference was not significant (P> 0.05), and in normal lesion both group were 55.8% (24/43), there was no difference. However, it was significant differencer between colorectal cancer and normal mucosa (P <0.05). AR protein expression in liver lesions were 7.0% (3/43), less than in colorectal lesions 27.9% (24/86), the difference was statistically significant (P <0.05), and the rate of AR protein expression in normal mucosa was 23.3% (10/43, liver metastasis group), the difference was not significant (P> 0.05). AR protein expression in colorectal cancer lesions between experimental and control group were 23.3% (10/43), 32.6% (14/43), the difference was not significant (P> 0.05), and in normal lesion were 23.3% (10/43), 37.2 % (16/43), the difference was not significant (P> 0.05). H0were, there was no significant difference between colorectal cancer and nomarl mucosa. In experiment group, ERβmRNA expression in colorectal cancer lesions were 33.3% (10/30), less than in normal mucosa 60%(18/30), the difference was statistically significant (P <0.05). In control group, ERβmRNA expression in colorectal cancer lesions were 43.3%(13/30), less than in normal mucosa 73.3%(22/30), the difference was statistically significant (P <0.05). However, for ERβmRNA expression in colorectal cancer lesions or in normal mucosa, there were no difference between experiment group and control group (P>0.05).CONCLUSION:ERβprotein is the mainly ER in CRC liver metastasis. ERβprotein expressions were not found in CRC liver metastases and primary lesions. In experimental group, ERβprotein and PR protein expression rates was ascending in liver lesions, cancer lesions and normal mucosa orderly. Which indicated that ERβprotein is more invasive, ERβis a protective factor for colorectal liver metastases. PR synergized with ERβand plays a protective role in liver metastasis. AR had low expression in colorectal cancer. Background: Colorectal cancer is a common digestive tract cancer, the incidence of malignant tumors in men ranked fourth and women ranked the third in recent years, with the living conditions and dietary habits change, the incidence of colorectal cancer showed an upward trend year after year, and 75% of the cases occurred in the general population. Although the study with the depth and the improvement of medical technology, the early diagnosis of colorectal cancer and post-operative survival rate has increased, but has yet to achieve a breakthrough, the overall sentiment satisfactory situation. Metastasis and recurrence is the main reason for the impact of CRC prognosis, liver is the most common metastatic sites from CRC, more than 20%~40% of patients with synchronous liver metastases, and 20%~25% of patients with metachronous liver metastases . To improve the early diagnosis of CRC and the cure rate is currently a major problem, select an effective drug prevention and to explore its role in the mechanism has become a very urgent task. Objective: To investigate the VEGF and EGFR in liver metastases from colorectal cancer and its relationship with clinicopathological characteristics.Materials and Methods: According to the first part of the selection and exclusion criteria, 43 cases of randomly selected patients with liver metastases of colorectal cancer as the experimental group, 43 cases of colorectal cancer with no metastases as a control group, immunohistochemical detection of VEGF and EGFR protein expression were presented in primary cancer lesions and the corresponding adjacent normal mucosa and liver organization, statistical analysis of VEGF and EGFR in the two groups its relationship with tumor clinicopathological characteristics were performed. Statistical methods: The data were analyzed use a two-sample comparison, Fisher's exact test,χ2 diverse segmentation method was used to calculate each two rates of varied rates,χ2 test was used for the comparison of the positive rate of different groups,correlation analysis Spearman correlated test , statistical significance was accepted at P<0.05, SPSS13.0 for statistical work has been completed windows package. The dates were analyzed using statistical software SPSS version13.0.Results: (1) VEGF protein in colorectal cancer lesions in the experimental group were 76.7 % (33/43), higher than the liver lesions and normal mucosa which were 58.1% (25/43) of 9.3% (4/43) ( P <0.05); VEGF protein expression in experimental group were higher than in control group at lesions of colorectal cancer (P <0.05); however, there were no significan difference at the normal mucosa between experimental group and control group (P> 0.05); (2) EGFR protein in colorectal cancer lesions in the experimental group were 79.1 %(34/43), higher than the liver lesions and normal mucosa which were 48.8% (21/43) of 11.6% (5/43) ( P <0.05); EGFR protein expression in experimental group were higher than in control group(58.1%, 25/43) at lesions of colorectal cancer(P <0.05); however, there were no significan difference at the normal mucosa between experimental group and control group(P> 0.05) ; (3) The relationship between VEGF and EGFR protein expression and clinicopathological characteristics found that VEGF and EGFR protein expression with gender, age, tumor site, histological type, depth of invasion associated with tumor differentiation was negatively correlated with liver metastasis and lymph node metastasis was positively correlated, and both are related to each other.Conclusions: (1) VEGF and abnormal expression of EGFR is the occurrence of liver metastasis of colorectal cancer in an important part. (2) VEGF and EGFR in colorectal cancer can be used as biological indicators, and can help to predict the occurrence of liver metastasis of CRC or CRC liver metastases to determine the prognosis for the future treatment of a new idea. Objective: to detect the affect of COX-2 in liver metastasis from colorectal cancer.Materials and Methods:43 cases with liver metastasis from colorectal cancer were selected as experimental group, and no-metastases cases of colorectal cancer were randomly selected as control group. Immunohistochemistry were used to discover the COX-2 protein expression in liver lesions, primary cancer and adjacent normal mucosa. Statistical methods: The data were analyzed use a two-sample comparison, Fisher's exact test,χ2 diverse segmentation method was used to calculate each two rates of varied rates,χ2 test was used for the comparison of the positive rate of different groups,correlation analysis Spearman correlated test , statistical significance was accepted at P<0.05, SPSS13.0 for statistical work has been completed windows package. The dates were analyzed using statistical software SPSS version13.0.Results: The liver lesions in the experimental group was in a higher COX-2 protein expression rate (19/43,44.2%), but lower than colorectal cancer lesions (79.1%, 34/43,), the difference was statistically significant (P <0.05), and expression of COX-2 protein at colorectal cancer site were higher than at normal mucosa (11.6%, 5/43), the difference was significant( P <0.05). there were no significant difference between experimental group and control group at colorectal cancer site(65.1%, 28/43,control group ) (P> 0.05). Two cases will be a comprehensive analysis of COX-2 protein expression rate and the relationship between clinicopathological factors and found that COX-2 protein expression and tumor differentiation was negatively correlated with lymph node metastasis and liver metastasis was positively correlated with gender, age, tumor site, histological type and depth of invasion is no clear correlation.Conclusion: 1.COX-2 protein in colorectal cancer over-expressed, in particular colorectal cancer liver metastases group of COX-2 protein expression was higher in colorectal cancer may be the occurrence and development play an important role.2. COX-2 protein expression level and the degree of tumor differentiation and lymph node metastasis was positively correlated.3. COX-2 protein expression level and patient gender, age, tumor location and depth of invasion is no clear correlation.4. COX-2 expression can be the basis to determine liver metastasis from colorectal cancer and provides a theoretical basis for regulation and control COX-2 protein expression to prevent tumor metastases.