Microvessel Density, Vascular Endothelial Growth Factor As Prognostic Indicators For Distant Metastasis And Survival Of Salivary Adenoid Cystic Carcinoma

The tumoral angiogenesis in the solid tumors, such as lung carcinomas and breast carcinomas, correlate significantly with their metastasis and prognosis. We aim to apply the immunohistochemical techniques to investigate the relationship between the microvessel density (MVD), the expression of vascular endothelial growth factor (VEGF) and their metastasis and prognosis for patients with salivary adenoid cystic carcinoma (SACC) after radical surgeries.After the follow-ups of 37 primary patients with SACC treated with radical surgeries from January 1981 to August 1997 in our department and oral maxillofacial department of the ninth people hospital of Shanghai, except the missing patients, the other 31 patients were recruited for our research. Then, the paraffin-bedded sections of the 31 patients were stained immunohistochemically, with anti-CD34-McAb marked the endothelial cells of the microvessls, and with anti-VEGF-McAb marked the carcinoma cells respectively. Subsequently, two pathologists who did not know about the clinical features and follow-up results of those patients, applied the 200-time optical microscope to evaluated the sections stained with anti-CD34-McAb to determine the MVD values individually, as well as, used the pathological image analysis system to individually determine the average optical density (OD) of sections stained with the ani-VEGF-McAb. Consequently the data of our research were analyzed with the SPSS 10.0statistic software package detailedly.The univariate statistical analyses of the log-rank test showed that MVD, OD, pathological types and TNM stages were all statistically significant variables for the survival of patients with SACC (P=0.047,0.000,0.000,0.024).Furthermore, among these reliable variables, MVD was more significant in the Cox proportional hazard model for the multivariate analyses (P=0.000).The MVD value were statistically significantly higher, in the subgroup with either death, or metastasis, or tumor-carried, worse pathological types, or advanced TNM stages, than their counterpart respectively( P=0.029 0.045 0.019 0.031 0.00), whereas there was not significant difference between the subgroups divided according to the evidence of recurrence. On the other hand, the OD value were also statistically significantly higher, in the subgroup with either death, or worse pathological types, or advanced TNM stages, than their counterpart respectively( P=0.037 0.013 0.014), whereas there were not significant differences between the subgroups divided according to the evidence of either recurrence, or metastasis, or tumor-carried. The results of Fisher exact test showed that the incidence of distant metastasis differed statistically significantly between the subgroups divided with the median of the MVD values (P=0.032) , while, of the incidence of recurrence, there was not statistical difference between the two subgroups. In addition, of the incidences either of metastasis orrecurrence, there were not significantly statistical differences between the subgroups divided with the median of the OD values. The stepwise linear regression test showed that the MVD values correlated positively with the OD values (P=0.029).As a result, MVD values, expression levels of VEGF, TNM stages and pathological types all have statistically significant correlations with the survival of patients with SACC, moreover, MVD values and TNM stages may be even regarded as independently prognostic indicators for patients with SACC. The MVD value could also be a prognostic indicator for the incidence of the distant metastasis of patients with SACC, whereas the OD value could not. The over-expression of VEGF in SACC might contribute to the MVD values increasing significantly.