The Study Of The Clinicopathology And The Relative Mechanism Of Perineural Invasion Of Pancreatic Cancer

In resent years, the incidence of pancreatic cancer, the most malignant disease in digestive system, has appeared to increase gradually in all over the world. About 40% patients had metastasis at the time of diagnosis, and perineural invasion (PNI) was the most common metastasis route for them. The prognostic factors were not uniform in the previous research. It was generally accepted that PNI is responsible for the high recurrence and pain, and was an independent prognostic factor in pancreatic cancer. Previous studies supported that cancer cells invaded the nerves under a plane of lowest resistance in perineurium, spread continuously along perineural space and formed a new metastasis focus in distance. But the exact molecular mechanism of PNI was not fully understood. Recent research put forward the hypothesis that some molecules in the specific perineural microenvironmentmay prompt proliferation and dissemination of tumor cells ObjectiveTo analyze the clinicopathologic factors correlating with patient's survival, observe the characteristic and pathway of PNI and find the factors correlating with it.To summarize the characteristic factors and explore the molecule mechanisms of PNI in pancreatic carcinoma. Methods1 , A retrospective analysis was performed on 52 cases of formalin pancreatic cancer tissues with complete clinicopathologic data. To select the valuable factors that could possibly influence the survival of pancreatic cancer, various clinicopathologic factors were analyzed as well.2 , Observe the pathway and degree of PNI, analyze the invasive route andexplore the correlation between PNI and clinicopathologic factors.3> (1) we ascertained the existence of neural through the immunohistochemical expression of NSE in 51 formolined pancreatic cancer tissue samples.(2) Using the immunohistochemical method, we analyzed a series antigen about PNI(3) Reverse transcription-PCR was used to analyze the mRNA of NGF and TrkA in twelve fresh pancreatic cancer tissues. (4) A correlation among the expressions of factors and PNI was evaluated. Results1 > The most frequent age of patients with pancreatic cancer ranged from 50-70 years, and patients were male predominant. The most common symptoms were discomfort of upper abdomen, bellyache. The prognosis of pancreatic cancer was very poor. Univariate analysis revealed a statistical difference among patient survival and PNI or tumor stage. Cox proportional hazard modeling demonstrated PNI was the significant independent indicator for survival.2> In this research, PNI was observed in 34 cases(65.4%). 20 cases showed the surrounding pathway of perineural invasion, and intraperineural invasion pathway in were seen in 30 cases. The results of univariate analysis showed that the major significant factors correlating with the existence and way and degree of PNI were tumor size or complete resection.3 > (l)NGF In pancreatic cancer with perineural invasion (PCPNI), the expression levels of antigen and mRNA were higher than that in pancreatic cancer without perineural invasion(PCNPNI) (P=0.039) .(2)TrkA There was no statistical correlation between antigen expression and PNI by IHC examination. Using the method of RT-PCR, TrkA mRNA were detected only in PCPNI with relatively low expression levels.(3)CXCR4 In the case of CXCR4 antigen, significant high expression levels were present in PCPNI comparatively with that in PCNPNI(P=0.042),and the correlation between levels of CXCR4 and the pathway of PNI was found to be significant(P=0.040).(4)TIMP-l The more the cancer cells expressed the TIMP-1, the more the intraperineural invasion pathway happened(P=0.018).(5)TIMP-2 There were statistical correlation among the expression of TIMP-2, the existence, the pathway and degree of PNI(P=0.000, P=O.OO6, P=0.000).(6)NCAM The expression levels of NCAM in PCPNI were significantly lower than that in PCNPNI, and there was negative correlation between them (P=0.031).(7) MMP-9 AND Ki-67 The difference were all not statistically significant between MMP-9, Ki-67 and PNI. (8)The protein levels of antigens were analyzed respectively, TIMP-2 expression correlated with MMP-9, TrkA or NCAM expression, and MMP-9 expression also correlated with TrkA or NCAM expression .Conclusion1 ^ PNI is an independent prognostic factor for the pancreatic carcinoma.2 ^ The cancer cells invade nerves by extending along the perineural space. The existence and degree of PNI correlate with tumor size and complete resection.3 > In pancreatic cancer, the high expression levels of NGF and CXCR4^ low expression levels of TIMP-2 and missing expression of NCAM all can promote the happenence of PNI through different pathways.