A Study On Mutation Of The PTEN Gene In Primary Esophageal Small Cell Carcinoma

Background and Objectives:Primary esophageal small cell carcinoma(PESCC) is the most common small cell carcinoma besides small cell lung cancer. Which has the main characteristics of high grade malignancy, rapid progress and poor prognosis. It is reported that the mobidity of PSCCE accounted for1-1.5%in the esophageal carcinoma, however, the mobidity of PSCCE accounted for7.6%in China. Due to the low incidence of PESCC, There exists a lack of consensus on the treatment of PESCC.Even if based on the operation of a variety of methods for the treatment of the PESCC but the prognosis is still unsatisfactory. The occurrence and development of tumors is closely related to the oncogene activation or inactivation of tumor suppressor genes leading to the abnormal signal transduction pathway. Thus, Both detecting the specific gene information carried by patients and selecting specific targeted therapies are very important for PESCC, which could extend the overall survival and improve the quality of life.PTEN is the first discovery gene has the double phosphatase activity of tumor suppressor gene. PTEN blocks the PI3K/PKB signal transduction pathwayby reducing the level of PIP3. PTEN plays an important role in cell apoptosis, proliferation, invasion and migration by negative regulation of signals of cell growth, such as, PI3K, MAPK and FAK. Some studies have found PTEN Mutation existed in gliomas, endometrial cancer, prostate cancer and other cancers. which the mutation has a close correlation to tumor development. In addition, PTEN affects some mportant biological processes including cell proliferation, invasion, metastasis and angiogenesis by activation of the tyrosine kinase activity result in promoting aberrant activation of downstream RAS-RAF-MAPK and PI3K-PTEN-AKT two major signal transduction pathways. EGFR mutation was recognized as an therapeutic target in many malignancies, and can be used to predict the efficacy of targeted therapy. As a key regulatory molecules downstream of EGFR signaling pathway, studies Have confirmed that K-ras and PI3K mutated in esophageal carcinoma,which closely related to tumor occurrence and development. This experiment is mainly to detect mutation of PTEN, EGFR, K-ras and PIK3CA genes in esophageal small cell carcinoma,, as the preliminary discussion on its mechanism in the occurrence and development of small cell carcinoma of the esophagus and looking for small cell carcinoma of the esophagus to provide experimental basis of individualized targeted therapies.Therefore, this experiment by detecting The mutation of PTEN, EGFR, K-ras and PIK3CA genes in PESCC tissues and analyzing possible pathways to the patients with PESCC tissue, analysis of possible pathways in order to provide the molecular target therapy to PESCC in future.Methods:1. Collected38cases of surgically resected pathological specimens of patients with small cell carcinoma of the esophagus, and the clinical pathological data such as patients’ age, sex, tumor location, TNM stage and so on.2. We applied HRMA, ARMS and pyrophosphate sequencing to detect the mutation of EGFR, PTEN, K-ras and PIK3CA genes in histopathological of PESCC and analyse their correlation with clinical pathological.Results:1.38cases pathological tissue samples of PESCC after HRMA detected found14cases of pathological specimens existed PTEN gene mutation, mutation rate was36.84%. PTEN gene mutations among14cases, including4cases of PTEN exon5,7cases of exon6,1case of exon8and exon5and exon6mutations in2cases together. There is no significant difference between the mutation of PTEN gene pathological and PESCC patients with clinicopathological features.2.38cases of the pathological tissue samples of PESCC found a case of a specimen was detected by ARMS method showed EGFR exon21L858locus existing mutation, mutation rate was2.63%, the rest of other EGFR mutations on18,19,20exon were not found.3. According to pyrophosphate sequencing assay,38cases PESCC pathological specimens found no mutations of K-ras and PI3KCA genes.Conclusions: 1. The mutation rate of PTEN gene is higher in PESCC, and the mutations are mainly concentrated on the exon5and6, which indicates PTEN may play a critical role in the development of PESCC.2. The EGFR gene mutation rate is low in PESCC, the mutation of this is closely related to the efficacy of EGFR-TKI. These sites may exist mutant in patients with PESCC has a certain effect.3. In this study, we didn’t find that K-ras and PI3KCA exsited mutation in PESCC, which suggested K-ras and PI3KCA may not play a critical role in the development of PESCC.