The Research Of Neurotropic Molecular Mechanism And Its Relationship With Clinical Factors In Adenoid Cystic Carcinoma Of Salivary Gland

Adenoid cystic carcinoma(ACC) is the second commonest malignant neoplasm in salivary glands. It has a known propensity for neural invasion, which will lead to frequent recurences. This neurotropism has brought great difficulties to the surgeons. But we don't recognize the mechanism of the perineural invasion in ACC thoroughly. The full-scale research for this mechanism and its relationship with clinical factors hasn't been seen in ACC.Objective: To observe the staining of GFAP, NT-3, Trk and NCAM in ACC, and analysis whether there is any relationship between the staining degree and neurotropism, clinical factors, in order to investigate the mechanism of perineural invasion of ACC and to provid the theoretical guidance of the clinical treatment for this tumor.Methods:94 cases of ACC were selected from February, 1977 to May, 2005 and were divided into two groups: NI(neural invasion) group and NNI(NO NI) group based on pathological view and clinical appearance. 94 cases of ACC, 10 cases of mucoepidermoid carcinoma, 10 cases of acinic cell carcinoma, 10 cases of neurilemmoma and 3 cases of saliyary gland had been immunohistochemical stained with antibody to GFAP, NT-3, Trk and NCAM. The counts of positive cells were studied with x~2 test and Binary Logistic model.Results:1. Partial positive staining for GFAP was present in ACC and neurilemmoma, and there was a stronger staining in NI group than in NNI group of ACC(P=0.000). But there was no positive staining of GFAP in acinic cell carcinoma. In addition, there was significant difference of GFAP staining in vary pathological types of ACC(P=0.001).2. Positive staining for NT-3 was present in ACC and neurilemmoma, and there was a stronger staining in NI group than in NNI group of ACC(P=0.000). But there was no positive staining in acinic cell carcinoma. In addition, there were significant differences of NT-3 staining in vary pathological types, recurrence and margin infiltration of Ace(P＜0.05).3. Weakly positive staining for Trk was present in ACC, and there was a stronger staining in NI group than in NNI group of ACC(P=0.000). There was strong staining in neurilemmoma, but no positive staining in acinic cell carcinoma. In addition, there were significant differences of Trk staining in vary pathological types and recurrence of ACC(P＜0.05).4. Weakly positive staining for NCAM was present in ACC, and there was a weaklier staining in NI group than in NNI group of ACC(P=0.000). There was positive staining in neurilemmoma, but no positive staining in acinic cell carcinoma. In addition, there was significant difference of NCAM staining in vary pathological types of ACC(P=0.042).5.There is positive correlation with the staining grade of GFAP, NT-3, Trk and NI. The negative correlation exist in the staining grade of GFAP and ACC types.Conclusions:1. Analysis of neurotropic mechanism in ACC:1.1 The Schwann cell diferentiation does occur in salivary adenoid cystic carcinoma. It possible is the biologic base of neurotropism in ACC.1.2 The NT-3 and Trk are exceedly expressed by ACC, which possibly promote cancer cells to invade the peripheral nerve.1.3 The NCAM is lowly expressed by ACC, which possibly lead cancer cells to proliferate out of control, to invade easily and to participate in perineural invasion indirectly.1.4 Multiplicity: the GFAP, NT-3 and Trk expressed by ACC possibly participate in the perineural invasion of ACC. The NCAM lowly expressed by ACC possibly promote the process of perineural invasion indirectly.2. Analysis of the clinic relationship with the staining of GFAP, NT-3, Trk and NCAM in ACC:2.1 Single-factor analyse:2.1.1 Highly expressed GFAP and Trk in solid type of ACC is possible coincidence with bad clinic behavior in solid type of ACC.2.1.2 In ACC, there were significant differences of NT-3 and Trk staining in vary pathological types and recurrence, significant difference of NT-3 in margin infiltration. Thus, the cancer cells with highly expressed NT-3 and Trk possibly possess the potency of bad differentiation, extensive invation and easy recurrence.2.1.3 The NCAM is lowly expressed in solid type of ACC, and there is bad clinic behavior in this type. Thus, the cancer cells with lowly expressed NCAM possibly proliferate strongly and easily prone to invad extensively.2.1.4 The higher staining of GFAP in solid type than in the other two types of ACC is possible correlation with malignant behaviorism.2. 2 Multiplicity: the highly expressed GFAP in solid type of ACC is possible coincidence with bad clinic behavior in solid type of ACC. The result of multiplicity doesn't support that highly expressed NT-3 and Trk could promote the recurrence of ACC.