ALDH1 as a prognostic marker for lymph node metastasis in OSCC

Abstract

Long-term survival in cases of head and neck squamous cell carcinoma, particularly oral squamous cell carcinoma (OSCC), remains a rare achievement in the field of clinical oncology. In recent years, the theory of cancer stem cells (CSCs) has emerged and been used to offer explanations for tumour recurrence and metastasis. The present aim was to investigate the role of aldehyde dehydrogenase 1 (ALDH1) as a CSC-marker for OSCC and to determine the role of p16ink4a, which is also a surrogate marker of human papilloma virus (HPV), in the expression of ALDH1. The study cohort comprised of 186 surgically-treated cases of OSCC. The primaries were located in the oral cavity. The expression of the CSC marker (CSCM) ALDH1 was evaluated via immunohistochemistry (IHC) of a tissue microarray. HPV detection was performed by polymerase chain reaction and an HPV Array kit. Furthermore, the IHC expression of p16ink4a was also analysed. Risk regression models as the Kruskal Wallis test was used to assess the association of CSCM and p16ink4a expression with tumour size and lymph node metastasis, and cox proportional hazards were analysed. Additionally, coexpression of the markers ALDH1 and p16ink4a was analysed with regard to associations with tumour classification. Overall, high expression of ALDH1 in lymph nodes was significantly associated with Union for International Cancer Control (UICC) stage IV (P=0.044) and T4 stage cancer (P=0.03). p16ink4a positivity, in cases of HPV negativity, was associated with worse survival rate compared with that of the total cohort (P=0.048). Collectively the data indicate that ALDH1 expression may be suitable for detection of unfavourable prognosis in OSCC patients, based in part on its apparent role as a marker of metastasis. HPV status was not statistically predictive of patient outcome or CSCM expression; however, p16ink4a remains a potential marker in HNSCC Further in vitro studies with ALDH1 and p16ink4a should be performed to evaluate the expression of ALDH1 and HPV in cell culture and to clarify the role of ALDH1 as a marker for increased invasiveness of OSCC cells.