Overexpression of ALDH1 and EMT marker profile are linked with unfavorable outcome in head and neck cancer

Abstract

Background The aim of this research was to assess the expression of aldehyde dehydrogenase 1 (ALDH1) and epithelial-mesenchymal transition (EMT) markers in head and neck squamous cell carcinoma (HNSCC), and to correlate them with the clinical and histopathological parameters of a patient cohort with follow-up over an 8-year period. Material and Methods For this, seventeen HNSCC and non-neoplastic adjacent epithelium (AE) samples were subjected to laser microdissection and real-time PCR to evaluate the mRNA expression of ALDH1, E-cadherin (E-CAD), N-cadherin (N-CAD), and vimentin (VIM). Also, immunohistochemistry was performed for ALDH1, E-CAD, N-CAD, and VIM in the tumor center (TC), invasion front (IF), and AE of the seventeen samples. Mann-Whitney, Kruskal-Wallis and Chi-square tests were used to correlate the mRNA and immunohistochemical expression with different variables, considering p <0.05. Kaplan-Meier curves were produced for local recurrence, regional metastasis and treatment. Results A mRNA overexpression of ALDH1 in primary tumors was associated with regional metastasis and a high ALDH1 immunostaining was related to metastasis and a worse patient outcome. Additionally, a favorable outcome was associated with the transition phase and an unfavorable outcome was associated with EMT event. An overall 26.9 months was observed with longer survival associated with surgery and radiotherapy. Conclusions However, due to the intense variability inherent to the indicator proteins in the EMT process, the complete profile markers related to this biological process should be continuous investigated. Key words: Aldehyde dehydrogenase 1, epithelial mesenchymal transition, head and neck cancer, squamous cell carcinoma, follow-up study.

Expression of aldehyde dehydrogenase 1A1 in oral squamous cell carcinoma and its correlation with clinicopathological parameters

“…The present study showed a linear relationship with high ALDH1A1 expression and TNM tumor staging, where ALDH1A1 expression increases as we move from lower T1 and T2 (31.4%) TNM stages to higher T3 and T4 (68.6%) TNM stages of tumor ( P < 0.04). This finding was in concordance with previous studies done by Ortiz et al .,[ 20 ] Szafarowski et al .,[ 29 ] Wang et al .,[ 30 ] and Vieira et al .,[ 31 ] which also suggested that higher stage cancer had high ALDH1A1 expression, hence more aggressive behavior. The above findings implied us to be more cautious about higher stage tumor, containing more tumor budding cells and cancer stem cells as compared to lower stages and have more probability of early metastasis.…”

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“…In 2007, Ginestier and his colleagues [23] found that ALDH1 is a marker of breast CSCs, marking the start of ALDH1 research in the field of CSCs. Since then, successive studies have confirmed that ALDH1 is a CSC marker in many cancers, including lung adenocarcinoma [ [24] , [25] , [26] ]. Its expression is closely related to the clinical prognosis of patients.…”

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“…High ALDH1A1 expression may also be a prognostic indicator in patients who have g-NECs. The aldehyde dehydrogenase (ALDH) family of proteins are present at high levels in stem cells as well as cancer stem cells in a number of malignancies [47][48][49] as well as NETs [50]. In gastric adenocarcinoma, overexpression of ALDH1A1 is significantly associated with depth of tumour invasion and LN metastases [51] and predicts poor prognosis in terms of overall survival and recurrence free survival.…”