Prognostic Significance of Podoplanin in Oral Squamous Cell Carcinoma

BACKGROUND: About 80-90% of all oral cancers worldwide are Oral Squamous Cell Carcinomas (OSCCs), making them the most common type of oral malignancy. Due to its propensity for lymph node metastasis, lack of accurate prognostic indicators, and delayed diagnosis, OSCC remains linked to high morbidity and mortality despite advancements in surgical and therapeutic approaches. A mucin-type transmembrane glycoprotein, Podoplanin (PDPN), is well known as a lymphatic endothelial marker and plays roles in metastasis, Epithelial-Mesenchymal Transition (EMT), and tumor progression and growth. The goal of the current study was to determine whether podoplanin's immunohistochemistry expression in OSCC and its association with other clinicopathological parameters could serve as a biomarker for the course and outcome of the disease. METHODS: This observational study was conducted over one year in the Department of Pathology in collaboration with the Department of Surgical Oncology, King George's Medical University, Lucknow. A total of 110 histopathologically confirmed, treatment-naïve cases of OSCC were included. Detailed clinical and demographic data were collected. Tumour specimens were processed and evaluated as per the College of American Pathologists (CAP) guidelines. Immunohistochemistry was performed using anti-podoplanin (D2-40 clone) monoclonal antibody. The expression of podoplanin was assessed semi-quantitatively using the German Immunoreactive Score (IRS), which combines staining intensity and percentage of positive tumour cells. RESULTS: The age of patients ranged from 23 to 75 years, with a mean of 45.3 years; the predominant age group was 31-40 years (35.5%). Males constituted 83.6% of the study population, and 89.1% had a history of tobacco, smoking, or alcohol use. The most commonly affected sites were the buccal mucosa (33.6%) and anterior tongue (30.9%). Most tumours were larger than 2.5 cm (58.2%) and exhibited a depth of invasion exceeding 10 mm (54.5%). Advanced pathological stage (Stage III-IV) was observed in 79.1% of cases, and 64.5% had nodal metastasis. Welldifferentiated tumours were most common (48.2%). Podoplanin expression ranged from weak (IRS 0-6) in 35.5% to strong (IRS >6) in 64.5%. Strong podoplanin expression correlated positively with larger tumour size, moderate to well-differentiated tumours, and nodal metastasis (N1-N3), although no significant association was found with early vs. late pathological stage. Interestingly, T4-stage and poorly differentiated tumours showed a tendency toward weak expression. DISCUSSION: The study confirms that strong podoplanin expression correlates with parameters indicative of tumour aggressiveness, including size, differentiation, and nodal involvement. These findings align with several prior studies, though the lack of significant association with pathological stage or overall survival underscores the complexity of podoplanin's role in tumour biology. The expression pattern-predominantly peripheral and membranous-suggests podoplanin may be involved in tumour invasion fronts and early carcinogenic events. CONCLUSION: The study findings suggest that podoplanin overexpression is significantly associated with tumour size, differentiation, and lymph node metastasis in OSCC, indicating its potential utility as a prognostic biomarker. Although the survival analysis did not demonstrate a statistically significant correlation with podoplanin expression, the trend toward higher mortality in patients with strong expression warrants further exploration. This study adds to the growing body of evidence supporting podoplanin's role in tumour progression and highlights its promise as a diagnostic and prognostic adjunct in oral cancer. Multicentric studies with larger cohorts and long-term follow-up are recommended to validate these observations.