BACKGROUND.: Lymphatic vessel density (LVD) and microvessel density (MVD) are important parameters for assessing the malignant potential of tumors and patient survival. In this report, the authors defined LVD as the density of D2‐40‐positive lymphatic vessels and MVD as the density of CD105‐positive microvessels per unit area of tissue. It was reported previously that vascular endothelial growth factor C (VEGF‐C) is a major modulator of LVD and MVD. The objectives of this study were to clarify the clinical and prognostic significance of both LVD and MVD in oral squamous cell carcinoma (OSCC) and to elucidate the lymphangiogenic and angiogenic activities of VEGF‐C in cancer tissues.METHODS.: In total, 110 OSCC tissue samples were evaluated for LVD, MVD, and expression of VEGF‐C using immunohistochemistry. Correlations among these parameters and clinicopathologic factors were examined.RESULTS.: LVD was significantly higher in tumors that had very high expression of VEGF‐C compared with tumors that had no/weak expression of VEGF‐C. LVD correlated well with lymph node metastasis (P < .001). MVD was correlated significantly with positive lymph node metastasis (P < .001) but not with VEGF‐C expression. In contrast, high expression of VEGF‐C was correlated significantly with advanced tumor status (P = .041). Survival rates were lower in patients who had higher LVD (P < .001), higher MVD (P = .0028), and strong VEGF‐C expression (P = .048).CONCLUSIONS.: Lymphangiogenesis predominantly influenced metastasis‐free survival. The current results suggested that LVD is a more useful tool than MVD and VEGF‐C for deciding on therapeutic strategies in patients with OSCC. Cancer 2007. © 2007 American Cancer Society.

A functional Gly388Arg variation in the FGFR4 gene has been reported to be associated with breast and colorectal cancer prognostic parameters. To further examine the functional role of this genetic polymorphism at the population level, we assessed the presence of the Arg388 allele in 142 breast carcinoma patients, 179 colorectal carcinoma patients and 220 general population controls with respect to an association with cancer prognosis and/or risk. No significant association with cancer risk, survival or any other prognostic parameters was observed in either breast or colorectal cancer. A pooled analysis of the present and published data on nodal status by FGFR4 genotypes revealed no association in either breast cancer [odds ratio (OR), 1.0; 95% confidence interval (CI), 0.7-1.4; 702 subjects] or colorectal cancer (OR, 1.4; 95% CI, 0.6-3.4; 260 cases). Thus, the FGFR4 polymorphism may not be relevant in predicting nodal involvement of breast cancer or colon cancer patients.

• TGF-β1 secreted from CAFs promote the migration and invasion of OSCC cells. • CAFs upregulate SOX9 expression of OSCC cells, possibly through inducing EMT. • The presence of CAFs is correlated with SOX9 expression in the invasive cancer nests. • The TGF-β/SOX9 axis between CAFs and OSCC cells facilitates cancer progression. • Targeting the TGF-β/SOX9 axis could be a potential novel target for OSCC.

Cholesterol plays an important role in cancer progression, as it is utilized in membrane biogenesis and cell signaling. Cholesterol-lowering drugs have exhibited tumor-suppressive effects in oral squamous cell carcinoma (OSCC), suggesting that cholesterol is also essential in OSCC pathogenesis. However, the direct effects of cholesterol on OSCC cells remain unclear. Here, we investigated the role of cholesterol in OSCC with respect to caveolin-1 (CAV1), a cholesterol-binding protein involved in intracellular cholesterol transport. Cholesterol levels in OSCC cell lines were depleted using methyl-β-cyclodextrin and increased using the methyl-β-cyclodextrin-cholesterol complex. Functional analysis was performed using timelapse imaging, and CAV1 expression in cholesterol-manipulated cells was investigated using immunofluorescence and immunoblotting assays. CAV1 immunohistochemistry was performed on surgical OSCC samples. We observed that cholesterol addition induced polarized cell morphology, along with CAV1 localization at the trailing edge, and promoted cell migration. Moreover, CAV1 was upregulated in the lipid rafts and formed aggregates in the plasma membrane in cholesterol-added cells. High membranous CAV1 expression in tissue specimens was associated with OSCC recurrence. Therefore, cholesterol promotes the migration of OSCC cells by regulating cell polarity and CAV1 localization to the lipid raft. Furthermore, membranous CAV1 expression is a potential prognostic marker for OSCC patients.