Expression Of Progastrin-releasing Peptide In Tumor Of Patients With Prostate Carcinoma, Non-small Cell Lung Cancer And Prognostic Significance Of Neuroendocrine Differentiation In Survival

Background and Objective: Malignant tumor pathological grade and clinical stage were more recognized prognostic indicators, but with heterogeneous and multi-differentiati on potential of tumor, estimating the prognosis is still relatively difficult. In recent years, neuroendocrine differentiation (NED) have an impact on the prognosis. Traditional view believed that only the carcinoid had the neuroendocrine cells, the study found that in prostate cancer, non-small-cell lung carcinoma (N-SCLC) had existing NED, too. Prostate cancer, N-SCLC with NED had a lot of difference with the others in a variety of biological behavior of tumor. Its shape was equivalent to the small cell lung cancer, but had often accompanied the composition with prostate cancer, lung adeno-, squamous cell carcinoma ,which may be related to patient's prognosis.In this study we evaluate the application of Progast rinreleasing peptide 31-98(Progrp 31-98)as a marker in the diagnosis of prostate cancer and N-SCLC, and observe the relationship between neuroendocrine differentiation and patients'postoperative survival.Methods: 1.During June 2002 to December 2007, patients with prostate cancer who were surgical treated were enrolled in this study. The tumor specimens were stained by NED markers : Progastrinreleasing peptide(Progrp31-98), neuron specific enolase(NSE) and chromogranin(CgA),These patients were positive for NED stain were also examined by electronmicroscope for the specific neuroendocrine granule. All enrolled patients were followed up to 7 months, and the maximum follow-up time was 70 months. Patients'postoperative survival for the NED positive expression and negative expression had been analyzed by the logistic analysis .The Cox proportional hazard model multivariate analysis was applied to observe the relationship among the prostate cancer with neuroendocrine differentiation and other prognostic factors .2. During January 2003 to June 2008, patients with non-small cell lung cancer who were surgical treated were enrolled in this study. To investigate the percent of neuroendocrine differentiation by NED markers: Progastrinreleasing peptide ( Progrp) 31-98 ,neuron specific enolase (NSE) and synaptophysin(SYN).All enrolled patients were followed up 5 - 66 months. The logistic analysis was applied to observe the NED positive expression and negative expression among the patients'postoperative survival. The Univariate Cox proportional hazard regression analysis was applied to observe the relationship among the non-small cell lung cancer with neuroendocrine differentiation and other prognostic factors .Results:1. In complete follow-up data of 43 cases,twenty -eight cases (28/43)were diagnosed as positive for NED stain. Among them ,65.1% (28/43) Progrp were positive ,20.9%(9/ 43) were CgA positive and 27.9%(12/43) were NSE positive .Progrp compared with CgA, NSE separately byχ2 test has statistically significant difference(P <0.01, P <0.05), the comparison between NSE and CgA was no significant difference (P >0.05). The specific NED granules were found by the electron microscope examination in 41.9 %(18/43) ,among them 14 cases are consistent with the Progrp positive expression.2. The logistic analysis showed that the prostate cancer with neuroendocrine differentiation patients'survival was significantly reduced (P<0.05).The Cox proportional hazard model multivariate analysis showed that the prostate patients'survival with neuroendocrine differentiation was significantly reduced (P <0.05) .The following factors were related to prostate patients'survival : the different Gleason score of the cancer (P <0.05) , and the NED markers reaction (P <0.05).No correlation with serum PSA and age of prostate cancer(P >0.05).3. Among forty-six N-SCLC cases ,47.8%(22/46) Progrp were positive ,23.9%(11/46)SYN were positive and 17.4%(8/46) NSE were positive.The logistic analysis was showed that the non-small cell lung cancer with neuroendocrine differentiation patients'survival was significantly reduced (P <0.05).The Cox proportional hazard model Univariate analysis was showed the following factors were related to the non-small cell lung cancer patients'survival: lung cancer cell differentiation (P <0.05),stages of the cancer (P <0.05 ),and the NED markers reaction(P <0.05) .Conclusion:1. Prostate cancer with neuroendocrine differentiation and the different Gleason score of the cancer are significantly related to the patients'postoperative survival.2.Progrp should be applied clinically as one of prognostic factors to evaluate the postoperative survival for prostate cancer patients.3.NSCLC-NED and the cancer cell differentiation are significantly related to the patients'postoperative survival. The NED markers should be applied clinically as one of prognostic factors to evaluate the postoperative survival for N-SCLC patients.