Expression Of FHIT Protein In Colorectal Cancer Tissue And Its Correlation With Pathology

Objective: Colorectal cancer is one of the most common gastrointestinal neoplasms and the incidence rate is rising year by year, though there has been extensively studied, However, the mechanism in the initiation and the development of the colorectal cancer (CRC) are poorly understood.The fragile histidine triad (FHIT) gene, a candidate tumor suppressor gene located at 3p14.2, has been shown to be involved in the carcinogenesis of many human tissues, including digestive tract tissues. Some research shown that the FHIT gene exhibits significantly decreased expression in human CRC compared to colorectal adenoma and normal colorectal tissue . FHIT gene 's abnormal structure or expression have been reported at home and abroad ,However, the function of the FHIT in the initiation and the development of the CRC are still not very clearly.This study are aim to find out the expression of FHIT correlation with pathology of CRC in North China,moreover,It may be provide the immunological basis for early diagnosis and prognosis of CRC.Methods:1.1 Specimens : 50 cases of CRC specimens were collected from patients operated in the Surgery Department of the Fourth Hospital of Hebei Medical University during September 2009 to February 2010. 44 cases of high and middle differentiated adenocarcinoma;6 cases of poorly differentiated adenocarcinoma; 7 cases of Dukes stage A, B phase; 43cases of Dukes stage C, D phase; 39 cases without lymph node metastasis, with lymph node metastasis in 11 cases. None of them received preoperative chemotherapy and radiotherapy or immunotherapy treatment, and so on.1.2 Immunohistochemistry was performed by using the SP method. Operation according to S-P kit instructions. FHIT was mainly located in the cytoplasm, some located in the nucleus. Inside of the cytoplasm or the nucleus particles appeares a brown positive signal. According to Tseng 's methods to have an comprehensive assessment, which includes the scope of staining intensity and staining.In each slide, 500 cells per core were counted. The relative intensity of cell immunostaining was evaluated semiquantitatively. The histological images were captured with an OLYMIPUSBX50 system microscope with an objective magnification 40X, through a video camera and digitized with appropriated software. A quantitative analysis of the immune reactions related to the total tissue area was performed We measured the percentage of positive immune reactivity with these antibodies in the tissue epithelium (normal and tumor). Both the extent and intensity of immunopositivity were considered when scoring FHIT protein expression. The extent of positivity was scored as follows: 0, <5%; 1, >5–25%; 2, >25–50%; 3, >50–75%;and 4, >75% of the colonic epithelial cells in the respective lesions. The intensity was scored as follows: And then staining intensity scoring: colorless, 0 points, 1 point light yellow, brown-yellow 2 points, tan 3 points; 9-12 are divided into strong positive (++), 5-8 are divided into weak positive (+), 0 - 4 is divided into negative (-)The final score was obtained by multiplying the extent of positivity and intensity scores, In order to replace an anti-PBS as negative control and using a known positive sections as positive controls.Results:1 FHIT protein expression and clinicopathological characteristics of colorectal cancer correlation: Low expression of FHIT protein in cancer histological grading of the distribution: poorly differentiated carcinoma 3 / 6, high school undifferentiated carcinoma 19/44;in TNM Staging T3,T4 cancers 15/43; T1,T2 cancers7/7; in lymph node metastasis group was 0/11, without lymph node metastasis was 22/39.Low expression of FHIT protein in cancer in the age group distribution:>53-year-old 14/31;≤53-year-old 8 / 19; in the gender group:the distribution of male 11/29, female 11/21; in the left colon group 7/16; right colon group 6 / 14; rectum group of 9 / 20; statistical analysis showed that the FHIT protein which was low expression in colorectal cancer have no significant related with age, sex, tumor location, differentiation, and so on(P> 0.05), but there was significant related with tumor grade and lymph node metastasis. (p<0.05)2 The positive expression rate of FHIT in normal colorectal mucosa was 96% (48/50) significantly lower than colorectal cancer mucosa which was 44% (22/50) (P<0.05).Conclusion:1 FHIT protein's deletion or reduce may have an important role in the occurrence or development of CRC.2 Pathology combined with detecting FHIT provides the necessary immunological basis for the early diagnosis and prognosis of CRC.