Immunohistochemical expression of CD44 in oral squamous cell carcinoma in relation to histomorphologic parameters and clinicopathological factors

Abstract

Objectives

Oral squamous cell carcinoma (OSCC) is characterized by its variable clinical course. In addition to the routinely used TNM/UICC systems, patient-specific prognostic/predictive biomarkers are needed. Promising biomarkers include the determination of the cancer stem cell (CSC) compartment, which can be identified by CD44 expression (amongst others).

Materials and Methods

A well-characterized cohort of 108 therapy-naïve OSCC with complete long-term follow-up and matched lymph node metastases were evaluated for CD44 expression by immunohistochemistry. CD44 expression was correlated with histomorphological characteristics (including tumor differentiation, tumor budding), clinicopathological parameters and follow-up data.

Results

Overexpression of CD44 was detected in 37% of OSCC within tumor center, 39% at the invasive margin and 16% of lymph-node metastases. CD44 overexpression at the invasive margin was significantly correlated with poor histopathological differentiation and specifically with high tumor budding activity and single cell invasion as signs of epithelial to mesenchymal tumor transformation (EMT). CD44 overexpression within tumor core region and in lymph node metastasis was identified as an independent prognostic factor for poor overall, disease-specific and disease-free survival in subsets of patients with advanced OSCC.

Conclusion

Our study demonstrates the association of CD44 with tumor aggressiveness and EMT as well as the independent prognostic impact of CD44 in a subset of OSCC, which underlines the role of tumor cell stemness as a key factor in malignant behaviour in this disease.

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