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

. 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 X 2 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. © 2003 Wiley Periodicals, Inc. Head Neck 25: 848–857, 2003