Motility-related protein-1/CD9 expression in head and neck squamous cell carcinoma

INTRODUCTION: Motility-related protein (MRP)-1/CD9 is implicated in cell adhesion and motility and was shown to be clearly involved in tumor prognosis and angiogenesis. Elevated MRP-1/CD9 expression on tumor cells has been linked to a favorable prognosis in breast cancer, colon cancer, lung cancer, and HNSCC. Because MRP-1/CD9 is associated with angiogenesis, it might play a role in tumor angiogenesis as well. METHODS: We analyzed MRP-1/CD9 expression in HNSCC specimens and cell lines by real-time RT-PCR and in HNSCC biopsy specimens and stromal vessels by immunohistochemistry. Kruskal Wallis and Chi2 test, univariate and multivariate Cox regression, and Kaplan-Meier methods were used for statistical analysis. RESULTS: Real-time and PCR RT showed elevated expression of MRP-1/CD9 in one (SCC25) of four HNSCC cell lines and two of six HNSCC patients, whereas two cell lines (SCC9 and JPPA) and one HNSCC patient had lower MRP-1/CD9 levels compared with other specimens. Immunohistochemistry demonstrated strong MRP-1/CD9 IR expression on tumor cells in 13 patients (39%), whereas 21 patients (61%) had less to medium MRP-1/CD9 IR expression. Increased MRP-1/CD9 expression on tumor cells was correlated with prolonged patient survival (p =.02) and a longer disease-free interval (p =.004), a diminished recurrence rate (p =.02), and lower stages of neck lymph nodes (p =.04). MRP-1/CD9 IR was also found in a subpopulation of vessels that seem to be less in tumor specimens than in normal mucosa (p <.0001). MRP-1/CD9+ vessels are podoplanin+ and are therefore regarded as lymphatic vessels. CONCLUSIONS: Our results revealed that elevated MRP-1/CD9 expression on HNSCC is linked to a favorable clinical outcome and confirmed reports of MRP-1/CD9 expression in other carcinomas. MRP-1/CD9+ vessels were found to be lymphatic in nature. The number and staining intensity of these vessels is decreased in tumor tissue, which suggests a stabilizing role for this protein in lymphangiogenesis.     

Differential expression of MUC1 and carbohydrate antigens in primary and secondary head and neck squamous cell carcinoma

BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), tumor markers may be helpful to evaluate prognosis accurately as well as to improve therapy selection. Detection of human MUC1 has been widely employed for the evaluation of carcinoma patients. This article aims to study MUC1, Tn, sTn, and Lewis antigenic expression in primary HNSCC, lymph node metastasis, and local recurrences. METHODS: We used immunohistochemistry, tissue homogenization and differential centrifugation, isopycnic density gradient centrifugation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blot. RESULTS: In primary tumors, MUC1 was detected in 80.0% of the samples; sLewis x in 23.2%, Lewis x in 45.6%, and Lewis y in 40.8%. Tn and sTn were found in 4.0% and 6.4% of samples, respectively. In metastatic lymph nodes, MUC1 showed a similar positive reaction as in primary tumors. Lewis y was detected in 20% lymph nodes whereas Lewis x, sLewis x, Tn, and sTn did not show differences. Some recurrences expressed MUC1 and only a few Lewis antigens, whereas Tn and sTn were not detected. CONCLUSION: In primary HNSCC and metastatic nodes, a high expression of MUC1 and Lewis antigens was detected that diminished in local recurrences. We also found that differentiated tumors mainly expressed a linear pattern of MUC1CT and Lewis x.