The Association Between Epithelial Proliferation And Intraepithelial Infiltrating Inflammatory Cells And The Detection Of HPV Infection In Esophageal Carcinoma High-risk Population

Background and ObjectiveChina is one of the highest incidence areas of Esophageal carcinoma in the world,especially ChaoShan area in sounthem China and LinZhou City in northern China. It's reportedin this 10 years, the incidence rate of esophageal cancer in ChaoShan area is 109.5/100,000 while83.2/100,000 in LinZhou City in 1998-2004. Our work team had studied the relationship of chronicesophagitis and esophageal cancer in ChaoShan area and we had confined that the population in ChaoShanarea were migarated from the central region of China. But there was still a controversy about the relationshipbetween inflammation and cancer. In 2005 Dec, we were invited to assist the endoscopic screening carried outby LinZhou City Tumor Hispital. So, the correlation between inflammation and esophagus cancerwas necessarily analied for the next research.Chronic esophagitis may act a key role in the carcinogenesis of esophagus cancer. Manyresearchers found the prevalence of chronic esophagitis in high risk area was obviously higherthan the lower one. Meanwhile, the incident of hyperplasia and atypical hyperplasia inepithelium accompanying esophagitis was higher than that of non-esophagitis.Our research team confined that the infiltrating cells in epithelium of esophagus weremainly T lymph-cell by IHC. HLA-DR as one of HLA classâ…¡antigens, acts a critical role inimmune response and immune regular mechanism. HLA-DR expresses on the surface ofactivated T lymph-cells, B lymph-cells, antigen presenting cells and vascular endothelial cells,etc. The expression of HLA-DR on peripheral blood lymphocytes can reflect the activated state.Since the correlation between HPV and esophageal cancer was found by Syijanen in 1982,more and more researches about HPV and esophageal cancer were carded out with differentdetection rate of HPV because of many objective reasons. Many researches show the infection ofHPV may be associated with esophagus cancer in high risk region. Some studies found thedetection rate was different in tissues of cancerous, paracancerous and normal mucosa. It was also reported that there was a high detection rate in non-cancer population in high risk region andthe rate gradually increased from normal mucosa to early cancer mucosa.Our research work was to observe the number of T lymphocytes infiltrating in epitheliumand the activated ones and its correlation with the degree of epithelial proliferation. Through thedetection rate of HPV in normal high-risk population, we did preliminary research about theHPV infection condition in high risk region and its relation with the degree of epitheliumproliferation.MATERIALS AND METHODSMaterialThe samples from 1480 symptom-free subjects aged from 40 to 70 years old, living inHejian town, Linzhou city. There were 558 male and 922 female in total.The population received investigation about address, living habit, Family Medical History,etc and the examination of body height, weight, Blood Pressure, and the HBV(s)-Ag, etc.The procedure of to draw materials is as following: firstly, exeminedthe gastrointestinaltract from esophagus to dodecadactylon; secondly, the biopsies from lesions of cardia of stomach and bodyof stomach were clamped; thirdly, the esophagus with Lugol staining and the esophagus lesions were clamped.Methods1. 1480 esophagus epithelium were stained with H.E, diagnosed pathologically andanalyzed statistically. In 301 subjects, which were selected randomly, the numbers ofthe inflammatory cells in the mucous membrane was counted under high power lens,and then the association between the numbers of inflammatory cells and the stage ofepithelial proliferation was analyzed. 2. Immunohistochemistry (IHC) straining against CD₃ and HLA-DR was performed byusing standard techniques. The positive cells were counted and the correlationbetween positive cells and the degree of proliferation was analyzed.3. Immunohistochemistry (IHC) and in situ hybridization(ISH) were performed for thedetection of HPV.RESULT1. The incidence of inflammation, atypical hyperplasia and early cancer was more andhigher as age developed. Especially in population of older than 50, the incidence ofinflammation, dysplasiaâ…¡and dysplasiaâ…¢was higher obviously. The number ofinflammation cells infiltrating in epithelium was correlated with the degree of epithelialproliferation.2. The number of CD₃⁺ cells infiltrating in epithelium was correlated with the degree ofepithelial proliferation. The expression of HLA-DR differed in group of normal,hyperplasia and dysplasia. The number of HLA-DR positive cells in dysplasia groupwas higher than the normal one.3. There was no protein of HPV 6, 11, 16, 18, 35 detected by immunohistochemistry andthe detection rate of HPV DNA for HPV5, 6, 8, 11, 16, 18, 26, 27, 30, 31, 33, 35, 39,40, 41, 42, 43, 45, 47, 48, 51, 52, 53, 54,55,57,58,59 was 32.9%(75/233).CONCLUTION1. The endoscopic screening is useful for the early detection of esophagus cancer. Thenumber of inflammation cells infiltrating in epithelium was correlated with the degreeof epithelial proliferation in high risk population.2. The infiltrating cells in epithelium of esophagus were mainly T lymph-cell in chronicesophagitis. The number of T cells infiltrating in epithelium was correlated with thedegree of epithelial proliferation but the activated T lymph cells. In dysplasia epithelium, the number of infiltrating HLA-DR⁺ cells was more than the normal epithelium.3. The detection rate of HPV DNA for HPV5, 6, 8, 11, 16, 18, 26, 27, 30, 31, 33, 35, 39, 40,41, 42, 43, 45, 47, 48, 51, 52, 53, 54, 55, 57, 58, 59 was 32.9%(75/228).