CD44 expression at the invasive tumor front: effect on patterning and prognosis in head and neck cancer

Abstract

The invasive tumor front (ITF) and pattern of invasion (POI) are significant prognosticators in head and neck cancer squamous cell carcinoma (HNSCC); this study evaluates the expression of CSC marker, CD44 at the ITF and their combined prognostic potential. POI, as scored by the invasive pattern grading score (IPGS), was correlated with CD44 expression in HNSCC cell line-derived xenografts. Immunohistochemical expression of CD44 was correlated with the ITF features in patients and their combined prognostic ability assessed by multivariate analysis, Kaplan–Meier plots, and Cox regression models. Assessment of cell line-derived in vivo models indicated that drug-resistant, CD44-enriched cell lines led to generation of xenografts with aggressive POIs (IV) at the ITF. In patients (N = 173), a near significant association of CD44 with IPGS (p = 0.05) was observed. CD44 (p = 0.02), along with differentiation (p = 0.04), and lymphoplasmocytic infiltration (LPI) (p = 0.03) were independent prognosticators of recurrence. Notably, IPGS and poorly differentiated tumors were predictors of recurrence in CD44high cohort (p < 0.05), while severe LPI was a good prognosticator only in CD44low cohort (p < 0.006). In the treatment naive cohort, the prognostic efficacy was confined to the early stage patients (p < 0.007). A multifactorial risk model significantly stratified patients based on outcome (p = 0.029). CD44+ CSCs at the ITF correlated with aggressive POI and both factors together were poor prognosticators of HNSCC.