Expression And Its Significance Of Estrogen Receptor Alpha36(Erα36) In Non-samll Cell Lung Cancer

Background:Pulmonary malignancy is the leading cause of cancer death in the world,. Even though lung cancer has historically been considered as a "man disease", and is still more frequent seen in male than female, women have been reported to suffer a greater susceptibility to develop such disease. Many researches have revealed a higher risk for women to develop lung carcinoma when consuming the same amount of cigarettes. In patients who have never smoked, the male/female ratio is notably1:3. Reasonably, estrogen has been proposed to be responsible for such gender difference. Many epidemiological studies reported that women undertaking estrogen replacement therapy had a higher risk of lung cancer, especially AC. But studies on estrogen receptors (ERs) in pulmonary malignancies turned out to be of dispute. Traditionally, ERs (ERa and ERβ) were a group of nuclear receptors which controlled the expression of target genes through estrogen-dependent and estrogen-independent genomic pathway. The expression rate of ERs in lung cancer varied drastically from0%to100%. Meanwhile, investigators have reported a rapid non-genomic pathway for estrogen in a number of malignancies including lung cancer. This indicated the existence of membrane ERs and a lot of work has been done to identify it. In2005, Wang et al successfully cloned a novel receptor for estrogen and named it ERa66(considering it is36kDa). The original ERa was then called ERa36. Instead of binding to target gene, ERa66mainly exist in the cytoplasm or on the cell membrane of breast cancer cells and exerts its effect through MAPK and/or PKB pathway. In this study, we detected the expression of ERa66in126NSCLC patients by immunohistochemistry to see if this novel receptor for estrogen is to any extent related to the clinical features of NSCLC.Methods and materials:1.126patients who underwent segmentectomies or lobectomies in Shandong Provincial Hospital in2008were randomly chosen and their resection specimens were collected.2. Using immunohistochemical staining, protein expression of ERa36, was detected in tissue specimens from126patients (79male and47female) who underwent resection for NSCLC. The immunoreactivity of ERa66was also studied as a comparison. The clinic pathological implication of these molecules was statistically analyzed. Subgroup analyses were performed for adenocarcinoma (AC) and squamous cell carcinoma (SCC).3. SPSS.16for Windows software was used for the result analyses. Values of P<0.05were considered significant.Results:ERa36has a higher expression than ERa66on NSCLC patients with AC in both female (P<0.001) and male (P<0.001). Besides, ERa36expression has a strong correlation with histology (AC:51/65, SCC:15/51, P<0.001) and had a significantly positive correlation with lymphatic metastasis (P=0.027) only in AC.Conclusion:ERa36had a high expression mainly in AC and high expression of ERα36was strongly correlated with more advanced regional lymph node metastasis in AC.