Clinicopathologic Initial Study And Investigation Of Mechanism Of Perineural Invasion In Adenoid Cystic Carcinoma

Obective1.To analyze the clinicopathologic features of adenoid cystic carcinoma(ACC), specially its morphologic features,and try to find out the prognostic factors which were related to perineural invasion.2.To investigate the mechanism of perineural invasion,and provide the theoretical reference for improving the therapeutic efficacy and living quality.Methods1.The subjects of this retrospective study were 42 patients suffered from ACC between 1983 and 2007 in the Stomatology Hospital of Tianjin Medical University. The clinic pathologic factors were collected including age,sex,primary tumor site, size,histological features,perineural invasion and TNM stage.The statistic analysis was performed between those parameters and perineural invasion.2.By immunohistochemical stain,to investigate the expressions of SMA,GFAP,GDNF,Ret and Ki-67 in ACC,and the statistic analysis was performed between those antibodies and perineural invasion.Results1.Among 42-case ACC,25 female and 17 male.Age is from 22 to 74.Average age is 47.29.Besides,18 cases in major salivary glands,23 cases in minor gland,and 1 case in other location.Plate gland is the most organ.Pain is the frequent symptom,presented in 54.76%cases.Perineural invasion can be found in 30 cases,and the rate is 71.43%,including 2 cases with vascular metastasis,1 case with lymphatic metastasis.In clinic diagnosis,9 cases were diagnosed as ACC,11 cases malignant pleomorphic adenoma or malignant salivary tumor,6 cases pleomorphic adenoma,2 cases gingival carcinoma,others without diagnosis.There are 5 cases inⅠstage,8 cases inⅡstage,13 cases inⅢstage,16 cases inⅣstage.There were no statistic differences between PNI and age,sex,primary tumor site. But there were statistic differences betweenⅠ+Ⅱstage andⅢ+Ⅳstage(P＜0.05), also between cribriform type and tubular type(P＜0.05),between cribriform type and solid type(P＜0.05),but no statistic difference between tubular type and solid type (P＞0.05).The Schwann's cell marker GFAP and the myoepithelial cell marker SMA proteins were co expressed in kytoplasm of the same onco-myoepithelial cells.Both GDNF and Ret were expressed in kytoplasm of the carcinoma cell of ACC. GDNF was expressed in neural fibro.But Ret was not expressed in neural fibro.In carcinoma cell of ACC,there were significant correlations between GFAP,GDNF and PNI,histological features,TNM stage(P＜0.05).There was no significant correlation between Ret and histological features,TNM stage(P＞0.05),but between Ret and PNI(P＜0.05).There was no significant correlation between Ki-67 and PNI (P＞0.05),but between Ki-67 and histological features,TNM stage(P＜0.05). Besides,There were significant correlation between GDNF and GFAP(P＜0.05), between GDNF and Ret(P＜0.05).But there was no significant correlation between GDNF and Ki-67(P＞0.05).Conclusions1.PNI is the biological behavior of ACC,whose incidence rate is high.There were significant correlations between PNI and TNM stage,histological features.The symptom of nerve involvement is usual in ACC.With the classic symptom,it is easy to diagnose.GFAP is expected to become an useful index to evaluate the PNI of ACC.2.PNI is a complex process.The Schwann cell differentiation occurs in onco-myoepithelial cells of ACC,and it may be the pathological histological base of PNI in ACC.GDNF combining with its receptor Ret improves the PNI of ACC.The sigal way with GDNF and Ret plays an important role in mechanism of perineural invasion in ACC.3.GDNF and Ret are expected to become useful indexes to evaluate the PNI of ACC,so that it is early to know the PNI.And it is possible to inhabit the sigal way to improve its treatment effectiveness.4.Ki-67 can be used to evaluate the severity of ACC.The relation between Ki-67 and PNI need a deep study.