The Expression Of SSTR2,SSTR5 And PR In Pulmonary Neuroendocrine Tumors And Their Clinical Significance

Background:The classification of lung and pleura tumor (2004) divided the pulmonary neuroendocrine tumors into four categories:the low grade typical carcinoid (TC), intermediate grade atypical carcinoid (AC) and the high grade large cell NE carcinoma (LCNEC) and small cell carcinoma (SCLC). According to statistics, pulmonary neuroendocrine tumors account for about 20%-25% of all lung cancer, about 90% of which are the high grade LCNEC and SCLC. LCNEC, and SCLC have a poor prognosis, and now treatment programs and their clinical application is limited. There need a new treatment ideas.There have been a large number of studies have found that tumor cells, vascular endothelial cells could express somatostatin receptors (Somatostatin receptor, SSTR). And there are five kinds of different molecular subtypes of somatostatin:SSTR1-5. Vitro and in vivo experiments have confirmed that somatostatin (Somastostatin, SST) and its analogues (Somatostatin analogue, SSA) could combined with SSTR on the cell membrane and that could inhibit the secretion of growth factors, inhibit endothelial cell proliferation, so as to achieve anti-angiogenesis effect. So SST and the SSA may develop into anticancer drugs of the more promising prospect. At present, the SSA include Octreotide(SMS 201-995), Vapreotide(RC-160), Lanretide(BIM-23014) and Seglitide(MK678),but their therapeutic effect had to been proved in clinic experiment in future.SSTRs have been found in a number of endocrine tumors, but their expression in pulmonary neuroendocrine tumors has been seldom reported in large quantity. It has been identified that pulmonary neuroendocrine tumors contains progesterone receptor (PR), but it's relationship with SSTRs is seldom reported too. The present study aims to find out the relationship between SSTR2, SSTR5 and clinical pathological factors, the correlation between SSTR2, SSTR5 and PR, the survival period of prognosis through studying the expression of SSTR2A, SSTR5, PR in pulmonary neuroendocrine tumors and normal tumor-adjacent lung tissues. It will shed light on the targeted therapy of LCNEC and SCLC.Objective:To investigate the expression of somatostatin receptor subtypes (SSTR2 and SSTR5) and PR in pulmonary neuroendocrine tumors, explore their relationships with angiogenesis, clinical parameters and prognosis.Subjects:There are 42 pulmonary neuroendocrine tumors paraffin-embedded specimens, which were removed in radical surgery and verified pathologically from Jan 2005 to Jul 2008, of Thoracic Surgery Department of Qilu Hospital. Among them,42 pulmonary neuroendocrine tumors tissue specimens consist of the investigation group, and the other 12 tumor-adjacent lung tissues consist of the contrast group.Methods:Immunohistochemical staining was used to detect the expression of SSTR2 SSTR5 and PR proteins in 42 cases of pulmonary neuroendocrine tumors and 12 tumor-adjacent normal lung tissues. Statistical analysis was done by SPSS 17.0, P<0.05 were considered significant.Results:SSTR2 is mainly located in cellular membrane, seldom stained in cytoplasm.SSTR5 is mainly located in cellular membarane and cytoplasm.PR is mainly located in nucleus.1.In the 12 tumor-adjacent normal lung tissues, the positive rates of SSTR2 and SSTR5 were 1/12 and 2/12 respectively. And all the 12 normal tissues nearby the cancer tissues are negative of PR.2. The positive rate of SSTR2 expression in pulmonary neuroendocrine tumors was 71.4%(30/42) and SSTR5 was 76.1%(32/42). While The positive rate of PR was 52.4%(22/42).3. SSTR2 and SSTR5 expression in lung neuroendocrine tumors is closely related to TNM stage and tumor type (P<0.05), but they have no significant correlation with sex, age, smoking status, tumor size and lymph node metastasis (P> 0.05). At the same group, PR expression is closely related to the type of lung neuroendocrine tumors (P<0.05), but not with sex, age, smoking status, tumor size, TNM stage and lymph node metastasis (P> 0.05).4. SSTR2 positive group of 3-year survival rate was 48.50%, higher than the negative group,22.16%, Log-rank test:3.86. The difference was statistically significant (P<0.05). SSTR2-negative group, the median survival was 32 months, lower than the positive group, the median survival of 36 months (P<0.05). SSTR5 expression group 3-year survival rate was 52.91%, higher than the negative group 28.22%, Log-rank test:3.81, and the difference was statistically significant(P<0.05). SSTR5 expression in the negative group,the median survival was 28 months,was lower than the positive group, the median survival of 38 months (P<0.05).Expression of negative PR 3-year survival rate was 50.44% higher than the positive 32.77%, and the difference had on statistically significant (P> 0.05). But the difference of the median survival between PR positive(32 months) and the negative group(36 months) had no statistically significant too (P> 0.05).5. The expression of SSTR2 and SSTR5 in pulmonary neuroendocrine tumor were both positively correlated with the expression of PR.Conclusions:The expression of SSTR2, SSTR5 and PR in Pulmonary neuroendocrine tumors suggests that the higher SSTR2, SSTR5 and PR expression, the better the prognosis, and longer survival (P<0.05). SSTR2, SSTR5 and PR are positively correlated.