The Correlation Of CCR7 And VEGF-C Expression And Lymphtic Microvessel Density With Lymphatic Metastasis In Laryngeal Carcinoma

Abstract:Objective:To detect the expression of CC Chemokine Receptor 7(CCR7) and blood vessels endothelial growth factor-C(VEGF-C) expression and lymphatic microvessel density values(LMVD) in laryngeal squamous cell carcinoma (LSCC), adjacent normal laryngeal mucosa and vocal cord polyps benign lesions of laryngeal, and to explore the relationship among the three and their relationship with lymph node metastasis of LSCC. Methods:Selecting from January,2008 to October,2009 surgical resection and pathological examination diagnosing the archived wax blocks of 40 cases LSCC tissues were as the experimental group from Affiliated Hospital of Luzhou Medical College Otolaryngology Head and Neck Surgery; 40 cases adjacent normal laryngeal mucosa tissues (more than 5mm away from the cancer confirmed by pathology to normal laryngeal mucosa) and 20 cases laryngeal polyp of vocal cord benign lesion tissues was as control group. The throat of all patients underwent preoperative high-resolution CT examination the throat, and did not receive chemotherapy or radiotherapy. The expression of CCR7, VEGF-C and D2-40 in all the organizations were detected by immunohistochemistry, D2-40 positive vessels were counted as LMVD value, combining with pathological data were analyzed by statistical methods, to analyze the relationship between CCR7, VEGF-C and LMVD and the relationship between clinical and pathological features of laryngeal cancer, as well as the relationship between the three factors. Results:The expression of CCR7 was significantly different in laryngeal carcinoma and adjacent normal mucosa and vocal cord polyps(P< 0.05), the expression of CCR7 was mainly in cytoplasm of carcinoma cells and /or membrane of carcinoma cells, a sheet of brown substance could be seen in the cytoplasm and/or membrane on the positive slide, but there were a few amount expression in LSCC adjacent normal'epithelial and almost no expression in the vocal cord polyps; There were positive in 24 positive cases and 16 negative cases of the expression of CCR7 expression in the 40 cases laryngeal carcinomas, the positive rate was 60.0%(24/40), CCR7 was closely related to the lymph node metastasis in LSCC, and it had no relaitionship with the sex, age, smoking, the cell differentiation, clinical classification and T stage. The expression of VEGF-C was also significantly different among the LSCC and the LSCC adjacent normal mucosa and the vocal cord polyps(P<0.05), the positive staining of VEGF-C which expressed mainly in the cytoplasm of LSCC was brown, there was a small amount expression in the vocal cord polyps and the negative control group; There were positive in 19 cases and negative in 21 cases of the expression of VEGF-C in 40 cases laryngeal carcinoma, the positive rate was 47.5%(19/40), the expression of VEGF-C was no significant difference with the tumor differentiation, clinical type and T classification (P>0.05); The positive rate and staining intensity of VEGF-C in the lymph node metastasis were higher than non-shift group, the difference was significant (P<0.05). D2-40 showing brown granular expressed in lymphatic endothelial cells more specifically, it had no expression in the vascular endothelial cells; The LSCC nests and peripheral and interstitial could be seen to be squeezed into the lymphatic cords, scattered or clustered distribution; The lymphatic microvessel density was significantly different among the LSCC and the adjacent normal mucosa and the vocal cord polyps(P<0.05); The lymphatic vessel density of lymph node metastasis group was significantly higher than non-shift group in LSCC, the difference was significant(P<0.01). In the 40 cases laryngeal carcinoma samples,17 cases were the expression of the VEGF-C and CCR7 and 15 cases were negative expression, Kappa concordance correlation test showed that the LSCC tissues expression of VEGF-C and CCR7 had a higher degree of agreement (k=0.600), and the coincidence between the two was statistically significant (P=0.000). LMVD mean was (17.57±3.27)/mm2 in the positive expression of VEGF-C tissues, the negative expression mean of LMVD was (10.26±3.77)/mm2,the two were significant differences (P<0.05). LMVD of the positive expression of CCR7 in LSCC that the LMVD was (19.05±5.33)/mm2, negative expression was (11.16±5.28)/mm2, comparing the two, P<0.01. Conclusions:(1) CCR7 was related to lymph node metastasis and VEGF-C was related to lymphangio-genesis in laryngeal cancer, they were in a synergistic effect to promote lymph node metastasis of laryngeal cancer; (2) The specificity and sensitivity of D2-40 which was a newly discovered lymphatic ideal marker labeled lymphatic were very well, it was significant correlation between high expression of LMVD expression in LSCC and marginal zone and lymph node metastasis in LSCC, suggesting that lymphangiogenesis play an important role in lymph node metastasis of LSCC; (3) With the expression of CCR7 increasing the intensity of VEGF-C positive grade went up, LMVD mean is also increaseed gradually, increaseing LMVD mean was in parallel with the positive intensity of CCR7, the expression of CCR7 was stronger, LMVD mean higher, it showed a significant correlation among CCR7, VEGF-C and LMVD; (4) CCR7, VEGF-C and LMVD and laryngeal cancer lymph node metastasis were closely related in laryngeal cancer, the joint detection of the three factors in endoscopic biopsy tissues can help predict the occurrence of lymph node metastasis in laryngeal cancer.