Prognostic and Predictive Factors in Gingivo Buccal Complex Squamous Cell Carcinoma: Role of Tumor Budding and Pattern of Invasion

Invasive tumor front (ITF) is the deepest three to six cell layers or detached tumor cell groups at the advancing edge of the tumor. Tumor budding is defined as presence of isolated single cells or small cell clusters scattered in the stroma ahead of the ITF and is characteristic of aggressive cancer. It is recognized as an adverse prognostic factor in several human cancers like colorectal, oesophageal, laryngeal cancers and more recently tongue cancers. However, the prognostic value of tumor budding has not been reported in GBCSCC. The aim of our study was to evaluate the role of pattern of invasion (POI) at the ITF, Tumor budding and other clinicopathological parameters in predicting nodal metastases and prognosis in GBCSCC. 33 patients with primary GBCSCC were prospectively evaluated at a tertiary care referral centre. Tumor budding and type of POI was examined in detail and data documented. Statistical analyses were carried out to assess the correlation of tumor budding, POI, and other clinicopathologic parameters (stage, grade of the tumor, tumor thickness, PNI, LVI) with nodal metastases and predict prognosis. Cox regression was used for both Univariate and multivariate analysis. Significant predictors of nodal metastases on Univariate analysis were male gender (p = 0.021), smoking (p = 0.046), Tumor budding (p = 0.014) and diffuse infiltrative/worst POI (p = 0.004), where as on multivariate analysis only worst POI was significantly associated with positive lymph nodes (p = 0.004). Presence of nodal metastases (p = 0.01) and tumor thickness >5 mm (p = 0.009) were independent negative prognostic factors on multivariate analysis. Significant single risk factor predictive of positive lymph nodes is worst POI in GBCSCC. Nodal metastases and >5 mm tumor thickness are independent risk factors for disease free survival.