Clinicopathologic Investigation And Initial Study Of Mechanism Of Perineural Invasion In Cervical Cancer

Objective:1.To analyze the relationship between perineural invasion (PNI) and clinical and histopathological features of cervical cancer and to evaluate the clinical significance of PNI of cervical cancer.2. To investigate the effect of never growth factor(NGF) and its receptors tyrosine kinase A (TrkA), P75 on PNI and to clarify the possible mechanism of PNI in cervical cancer.Method:1. Retrospective review identified 339 patients with cervical cancer stages Ibl-Ⅱb who underwent radical hysterectomy in the Affiliated Tumer Hospital of Guangxi Medical University between March 2013 and December 2015. Detected of PNI by S-100 immunohistochemical staining. The association between PNI and clinical and histopathological features of cervical cancer was evaluated based on univariate and multivariate analyses.2. Radom selected 20 patients of cervical cancer with positive PNI,20 patients with negative PNI, and 20 patients of normal cervix..By using SP immunohistochemistry, we studied the expressions of NGF and its receptor TrkA, P75 in the three groups and analyzed their relationships with perineural invasion and other clinicopathologic parameters.Result:1.PNI of cervical cancer was identified in 51 of 339 (15%) cervical cancer patients. Univariate analysis demonstrated that PNI was associated with clinical stage, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and lymph node metastasis (P<0.05), but not associated with age, histopathological types, tumor grade, parametrial involvement (P>0.05). Multivariate analysis suggests that tumor size, depth of invasion and LVSI were associated with PNI of cervical cancer (P<0.05).2. The immunoreactivity of NGF and TrkA were intensely present in cytoplasmic and membranous in the cervical cancer cells (positive rate= 100%and 97.7%, respectively), but weakly present in normal uterine cervix, (positive rate=80%and 55%, respectively), the difference were significant (P=0.017, P=0.000, respectively). While the immunoreactivity of P75 was weakly present in membranous in the cervical cancer cells, but intensely present in normal uterine cervix of basal cell (positive rate=32.5%,100%, respectively), the difference were significant (P=0.000).The expression of NGF, TrkA and P75 in nerve fibers or perineurium were low, medium and high, respectively.3. The expression of NGF was significantly stronger in PNI group than that in non-PNI group(P=0.001). While expression of TrkA and P75 was not significantly associated with PNI (P=0.194 and 0.190, respectively). Moreover positive intensity of NGF has a positive correlation with LVSI (P=0.000), and P75 has a positive correlation with clinical stage (P=0.034).Conclusion:1.PNI was significantly associated with clinical stage, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and lymph node metastasis. Tumor size, depth of invasion and LVSI were risk factors of PNI. PNI may be a new risk factor candidate for cervical cancer.2. The overexpression of NGF and TrkA, while low expression of P75 may be have some effects on progress of cervical cancer.3. NGF and TrkA mainly expressed in cervical cancer cells, and partly expressed in never, while P75 mainly expressed in never, and partly expressed in cervical cancer cells. The positive intensity of NGF was significantly associated with PNI. NGF, TrkA and P75 may play important role in the process of perineural invasion in cervical cancer.