Hidetoshi Kawaguchi, Adel K. El-Naggar, Vali Papadimitrakopoulou, Hening Ren, You-Hong Fan, Lei Feng, J. Jack Lee, Edward Kim, Waun Ki Hong, Scott M. Lippman, Li Mao

From the Departments of Thoracic/Head and Neck Medical Oncology, Biostatistics and Applied Mathematics, and Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX

Corresponding author: Li Mao, MD, Department of Thoracic/Head and Neck Medical Oncology, Unit 432, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: lmao@mdanderson.org

Purpose: Oral leukoplakia (OPL) is a heterogeneous oral lesion with an increased oral cancer risk. Current clinical parameters cannot predict the potential of malignant transformation in patients with OPL. We have shown that podoplanin, a lymphatic endothelial marker, is highly expressed in oral cancer and some oral premalignancies. The purpose of this study is to determine a role of podoplanin in predicting oral cancer development in patients with OPL.

Patients and Methods: Podoplanin expression was determined in 150 OPL patients with long-term follow-up using immunohistochemistry. Association between the protein expression patterns and clinicopathologic parameters including oral cancer development during the follow-up were analyzed.

Results: Fifty-six (37%) of the 150 OPL patients exhibited podoplanin expression in the basal and suprabasal layers and were classified as podoplanin positive. Podoplanin positivity was more frequent in older patients (P = .016), females (P = .020), and dysplastic lesions (P = .040). Patients with OPL that was podoplanin positive had significantly higher incidence of oral cancer than did those whose OPL was podoplanin negative (P = .0002). In the multivariate analysis using histology and podoplanin as cofactors, podoplanin was the only independent factor for oral cancer development (hazard ratio = 3.087; 95% CI, 1.530 to 6.231; P = .002). Importantly, oral cancer risk can be further stratified by considering both histology and podoplanin information.

Conclusion: Podoplanin is frequently expressed in OPL. Together with histology, podoplanin may serve as a powerful biomarker to predict the risk for oral cancer development in patients with OPL.

Supported in part by National Cancer Institute Grants No. PO1 CA52051, PO1 CA106451, P50 CA97007, and P30 CA16672, and by the Uehara Memorial Foundation (H.K.)

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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