Correlated Research On Roles Of GDNF And Its Receptor On Perineural Invasion Of ACC

Objectives1 To investigate the possible mechanism and roles of GDNF and one of its receptors-Ret in perineural invasion (PNI) of salivary gland adenoid cystic carcinoma (ACC).2 To investigate the possible mechanism and relations between effects of MMP-9,NF-κB,VEGF,Integrinβ1 Bcl-xL in matrix-degrading,angiogenesis,adehesin,anti-apoptosis and perineural invasion of salivary gland ACC.Methods1 Totally 42 ACCs,5 acinic cell carcinomas,5 normal salivary gland tissues were included in the present study. Immunohistochemical staining S-P method was used to detect the expressions of GDNF,Ret,MMP-9,NF-κB,VEGF,Integrinβ1,Bcl-xL in ACCs, acinic cell carcinomas, normal salivary tissues.2 All data analyszs by Chi Square test,Fisher's Exact test,Spearson Correlation were performed on SPSS 16.0 software. P values less than 0.05 were considered statistically significant.Results1 GDNF and its receptor Ret were highly expressed in ACC cells and normal ductual cells, and GDNF was also expressed in nerves adjacent ACC. The positive expression rate of GDNF,Ret in ACC was 69.05%(29/42),69.05%(29/42), respectively. Expression of Ret was correlated with GDNF(r=0.554, P=0.000).The positive expression rate difference between early clinical staging 38.46%(5/13) and advanced clinical staging 82.76%(24/29) of expression of GDNF was statistically significant (P=0.012), and so was the positive expression rate difference between histological classification and grading groups 91.67%(11/12),45.00%(9/20),90.00%(9/10) of expression of GDNF (P=0.006).2 NF-κB,MMP-9,Integrinβ1 were all positively expressed in ACC cell cytoplasm, NF-κB in nuclei occationally. The positive expression rate was 69.05%(29/42),66.67%(28/42),61.90%(26/42), respectively. The differences between the expression of GDNF,NF-κB,MMP-9,Integrinβ1 in PNI group and non-PNI group were all statistically significant(P=0.000,P=0.005,P=0.011,P=0.001, respectively). Expressions of NF-κB,MMP-9,Integrinβ1 were correlated to that of GDNF(r=0.443,P=0.003; r=0.401, P=0.009, r=0.535, P=0.000, respectively). Expressions of MMP-9 and Integrinβ1 were correlated to that of NF-κB(r=0.501, P=0.001, r=0.429,P=0.005). Expression of MMP-9 was correlated to that of Integrinβ1,VEGF(r=0.381, P=0.013; r=0.652,P=0.000). The positive expression rate differences between early clinical staging group 30.77%(4/13),38.46%(5/13),38.46%(5/13) and advanced clinical staging group 75.86%(22/29),79.31%(23/29),82.76%(24/29) of expression of Integrinβ1,MMP-9,NF-κB were statistically significant (P=0.015,P=0.025,P=0.012, respectively).3 VEGF,Bcl-xL were both positively expressed in ACC cell cytoplasm. The positive expression rate was 59.52%(25/42),57.14%(24/42), respectively. The differences between the expression of VEGF,Bcl-xL in PNI group and non-PNI group were all stayistically significant (P=0.011,P=0.000, respectively). Expression of VEGF,Bcl-xL was not correlated to that of GDNF but NF-κB(r=0.392, P=0.010, r=0.357, P=0.020, respectively). The positive expression rate difference between early clinical staging group 23.08%(3/13) and advanced clinical staging group 75.86%(22/29) of expression of VEGF was statistically significant (P=0.004).4 Expression of GDNF in pain-group and non-pain group was statistically different (P=0.033).Conclusions1 GDNF and Ret were both positively expressed in ACC cytoplasm, and GDNF also in neighboring nerves, indicating that there is autocrine of GDNF in ACC, which plays important roles in the process of PNI.2 GDNF possibly being as NF-κB activator activates the related singling pathways, and causes MMP-9 and Integrinβ1 transcription and expression. Then MMP-9 degrades matrix, and changes around the tumor microenvironment, and Integrinβ1 may enhance its adhesion ability in the process, promoting ACC cells invading nerves.3 Angiogenesis and enhance of antiapoptosis faciliates ACC cells invading nerves, but, intriguingly, the expression of VEGF and Bcl-xL was not correlated with GDNF, possibly other factors participating the process.4 GDNF may correlate the occurence of neurological symptoms in ACC cohorts.