Expression And Clinical Significance Of HMLH1、ERCC1 And Ki67 Proteins In Esophageal Squamous Carcinoma

Objective: Esophageal carcinoma is one of common gastrointestinal malignancy cancer in our country.Development of esophageal carcinoma involved multiple gene mutations through multiple stages,multiple factors,and multiple time accumulated.Genome Stability often relies on integrated damage repair system in normal cell.Two important repair patterns are mismatch repair(MMR)and nucleotide excision repair(NER).Mismatch repair gene(hMLH1)is one of the most important gene in MMR system,which mainly corrects the base pairing mistakes during DNA replication,restructuring and genetic damage.Excision repair cross complementary 1(ERCC1)is marked genes in NER system which can repair damaged structure of chromosomes.Ki-67 is closely related to cell proliferation,which can reflect the proliferation rate of cancer cells.This paper mainly studied the influence of mismatch repair system on development of esophageal squamous cell carcinoma(ESCC)and the feasibility of individualized treatment and clinical prognosis judgement by examining the expressions of hMLH1 protein in the MMR system and ERCC1 protein in NER system between ESCC and normal esophageal squamous epithelium.Methods: Selected 120 cases of ESCC and 20 cases of normal esophageal epithelial tissues from the First Affiliated Hospital in Hebei North University to detect protein expressions of hMLH1,ERCC1 and Ki67 by SP immunohistochemistry.To analyze the relationship between expressions of three proteins and clinical pathologic characteristics,and to study the correlation between cellular proliferation and the two proteins.Results:1 Protein expression of ERCC1: Positive expression rate of ERCC1 in ESCC group(34.2%)was significantly lower than that in normal esophageal mucosa(60.0%)(P<0.05).ERCC1 expression was related to differentiation degree: positive expression rate of ERCC1 in high or moderate differentiation carcinoma groups(70.0%,36.2%)were both significantly higher than that in poorly differentiated carcinoma group(14.3%)(P<0.05).ERCC1 expression was associated with lymph node metastasis: positive expression rate in lymph node metastasis group(12.2%)was significantly lower than that in without lymph node metastasis group(45.6%)(P<0.05).But ERCC1 expression had no significant relationship with patients’ gender,age,depth of tumor invasion and clinical stage(P>0.05).2 Protein expression of hMLH1: Positive expression rate of hMLH1 in ESCC group(39.2%)was significantly lower than that in normal esophageal mucosa(90.0%)(P<0.05).hMLH1 expression was related to differentiation degree: positive expression rate of hMLH1 in high or moderate differentiation carcinoma groups(60.0%,46.6%)was significantly higher than that in poorly differentiated carcinoma group(19.0%)(P<0.05).h MLH1 expression was also associated with lymph node metastasis: hMLH1 expression in lymph node metastasis group(19.5%)was significantly lower than that in without lymph node metastasis group(49.4%)(P<0.05).But hMLH1 expression had no significant relationship with patients’ gender,age,depth of tumor invasion and clinical stage(P> 0.05).3 Protein expression of Ki67: Positive expression rate of Ki67 in ESCC group(62.5%)was significantly higher than that in normal esophageal mucosa(0.0%)(P<0.05).Ki67 expression was related to infiltration depth: positive expression rates of T1 or T2 group(0.0%,47.2%)was significantly lower than that of T3 or T4 group(71.4%,87.5%)(P<0.01).Ki67 expression was related to differentiation degree: positive expression rate of Ki67 in high or moderate differentiation carcinoma groups(35.0%,65.5%)was both significantly lower than that in poorly differentiated carcinoma group(71.4%)(P< 0.05).Ki67 expression was associated with lymph node metastasis: expression of Ki67 protein in lymph node metastasis group(85.4%)was significantly higher than that in without lymph node metastasis group(50.6%)(P<0.05).But Ki67 expression had no significant relationship with patients’ gender,age,and clinical stage(P> 0.05).4 Correlation analysis: Expressions of ERCC1 and Ki67 protein had significantly negative correlation(P<0.01,r=-0.386);and expressions of hMLH1 and Ki67 protein had also significantly negative correlation(P<0.05,r=-0.225).But expressions of ERCC1 protein had no relationship with hMLH1(P> 0.05,r=0.142).Conclusions:1 The expressions of ERCC1 and hMLH1 protein were up-regulated,while Ki67 was down-regulated.2 The expressions of ERCC1,hMLH1 and Ki67 were associated with the occurrence and development of esophageal cancer,which could be used as biological indicators to evaluate the clinical pathological characteristics of esophageal squamous carcinoma.3 To detect protein expressions of ERCC1 and hMLH1 could understand the proliferation of esophageal cancer cell,which is helpful to evaluate the progress of esophageal cancer,and also to provide reference for clinical reasonable chemotherapy regimens.