Mechanism Of Micrometastasis And Lymphangiogenesis In The Process Of Perineural Invasion In Pancreatic Adenocarcinoma

Objectives:As one of the most malignant human diseases,pancreatic carcinoma is characterized by difficult early diagnosis low resection rate poor prognosis.To overcome the disease,we need to comprehend its biological characteristics and seek corresponding countermeasure. Perineural invasion was reported in 70% to 100% of patients with pancreatic cancer.Although the exact mechanisms are unknown, perineural invasion negatively impacts prognosis for pancreatic cancer patients. Neural invasion is a special metastatic route in pancreatic cancer and responsible for the high recurrence and distant metastasis in curatively resected cases. It is important to study the perineural invasion to improve the dignosis and treatment of pancreatic cancer . This experiment is to analysis perineural invasion of pancreatic carcinoma and study lymphatic vessel density (LVD) and lymphatic vessel invasion(LI) by immunohistochemistry methods. Furthermore,this study will approach the mechanism of micrometastasis and lymphangiogenesis in the process of perineural invasion in pancreatic adenocarcinoma.Methods:A total of 1800 serial sections including intratumoral tissues periturmoral and nontumoral tissues the structure surrounding the SMA and lymph node were obtained from 18 pancreatic cancer specimens. They were subjected to conventional hematoxylin/eosin staining and immunostaining for Cytokeratin 19 and the lymphatic marker D2-40.We measured the lymphatic vessel density (LVD) by immunostaining with specific lymphatic endothelium marker, and analysis the relationship between perineural invasion and lymphatic vessel invasion.RESULTS: Perineural invasion was observed in 14 patients(77.8%) . Extra-pancreatic neural plexus invasion by pancreas carcinoma cells was detected in 12 of 18 cases (67.7%) with intra-pancreatic neural fiber invasion.The other 2 belongs to intra-pancreatic neural fiber invasion. Perineural invasion was not significantly associated with patient age. gender, lymph vessel invasion tumor size and tumor location(P > 0.05),but was significantly associated with JPS clinical stages ( P < 0.05 ) .Thin-walled, erythrocyte-free vessels staining with lymphatic markers (D2-40) were found.Intratumoral LVD (4. 1±1.1) was significant lower than periturmoral (12.1+2.2) and nontumoral LVD (10.2±1.0) (P<0.01 and P<0. 001, respectively). Lymphatic vessels invasion can be observed easily by immunostaining with D2-40.There seemed to be a distribution correlation between lymphatic vessel invasion and neural plexuses invasion (P<0.05) .CONCLUSIONS:Neural invasion is an important prognostic factor for the recurrence of pancreatic carcinoma after pancreatectomy. Because of its high incidence, pancreatectomy with extended radical retroperitoneal dissection should be considered as a basic procedure in the treatment of pancreatic carcinoma. Our data indicated the lymphatic vessels distribution in pancreatic cancer samples, and peritumoral lymphangiogenesis may promote the malignant progression of invading pancreatic peripheral nerves.