The Relationship Between The Expression Of NGF And Its Receptors And Perineural Invasion Of Oral Tongue Squamous Cell Carcinoma

Objective:(1)Continuous slice hematoxylin and eosin staining(HE)staining and S100 immunohistochemical staining(IHC)method were used to identify the same sample of oral tongue squamous cell carcinoma,and the differences in the specificity of nerves(fibers,bundles)were compared between the two methods.perineural invasion(PNI)of tongue cancer with different clinicopathological parameters were also compared to understand the PNI characteristics of oral cancer.(2)To compare the expression of nerve growth factor(NGF)and its receptors p75 neurotrophin receptor(p75NTR)and tropomysoine receptor kinase A(Trk A)with different clinicopathological parameters of tongue cancer,and to compare the expression of NGF and its receptor p75NTR(NGFR),Trk A with PNI,and understand the mechanisms.Methods:13 cases of well-differentiated,11 cases of moderately-differentiated,and 5 cases of poorly-differentiated tongue cancer specimens,all were made continuous slices.(1)The nerve(fibers,bundles)were stained with HE and neuron-specific antibody(S100)IHC and the nerves were judged by comparing the two methods.The advantages and disadvantages of the two methods was evaluated.The total number of nerve bundles and the number of PNI in each specimen were determined and counted,and compared the differences between different clinical pathological indicators.(2)The expression of NGF,Trk A and p75 NTR were detected by immunohistochemical staining.The difference in positive expression rates between different clinical pathological indicators,and their relationship with the PNI of the corresponding indicators were compared statistically.Results:(1)Among HE staining,S100 immunohistochemical staining and p75 NTR immunohistochemical staining,we found that p75NTR-stained nerve bundles were highly specific and significantly better than the S100 method.Concordance rate(p75NTR coincidence rate 98%,S100 coincidence rate 71%)was significantly higher than S100.The most common false positive for S100(p75NTR false positive rate 2%,S100 false positive rate 26%)was indistinguishable from striated muscle.Moreover,compared with HE(p75NTR compliance rate 100%,HE compliance rate 78%)method,p75 NTR was significantly higher than that of HE.(2)There was no significant difference in the average number of neuron bundles/case in tongue cancer with different degrees of differentiation and T status.The number of PNIs was also small,and the PNIs number of well-differentiated squamous cell carcinomas was very low.Compared with moderately-differentiated squamous cell carcinomas,the peripheral cancer tissue infiltration rate(PNI / total number of nerve bundles)of well-differentiated squamous cell carcinomas was significant high(P = 0.00 <0.05),and there was no significant difference between moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma(P = 0.702> 0.05).On the other hand,there was no significant difference among three T statuses.(3)There was no significant difference in the average number of neuron bundles/case between the two groups(with and without lymph node metastasis group)(P>0.05),It is suitable for using Paired sample Chi-square test that the peripheral cancer tissue infiltration rate in No lymph node metastasis group was lower than that in lymph node metastasis group(p = 0.000<0.05),the difference was statistically significant.(4)There was no significant difference in the expression rates of NGF and its receptors in different grades and T status of squamous cell carcinoma,and with or without lymph node metastasis(p>0.05).(5)There was no difference in the expression of NGF and its receptors in distant cancerous nest tissues and in infiltrating squamous cancer tissues around nerves.(p>0.05)The expression of NGF in carcinoma tissues was higher than peritumour normal epithelial tissues(p<0.05).However,there was no significant difference in the expression of its receptors between carcinoma tissues and peritumour normal epithelial tissues(p>0.05)Conclusion:(1)We found for the first time that p75 NTR can identify nerve bundles better than S100 with more specificity and less non-specific staining;however,there may be staining of microvasculature and false positives for small nerve fibers.If combined with HE and S100 staining,it can be used to accurately identify nerve bundles,which is expected to become a new and better neural marker.(2)Oral squamous cell carcinoma is not strongly neuropathic.Well-differentiated squamous cell carcinoma has very little infiltration around the nerves,and moderately and poorly differentiated squamous cell carcinomas have a small amount of PNI.There is no significant relationship between the expression of NGF and its receptor and PNI.However,PNI is related to lymph node metastasis.The mechanism may be that the invasive ability of squamous cell carcinoma itself causes the PNI of the nerves through invading the region.