ABSTRACT
Hypoxia-inducible factor-1α (HIF-1α) has been shown to be involved in cancer metastasis in several cancer types. There is however conflicting evidence of HIF-1α expression with oral cancer prognosis. Therefore, this study set out to investigate HIF-1α overexpression and its relationship with the aggressiveness and grade of oral squamous cell carcinoma (OSCC) and to explore the diagnostic potential of HIF-1α overexpression in OSCC in a cohort of Pakistani patients. Immunostaining of HIF-1α was performed on 54 OSCC and 14 normal oral mucosa (NOM) tissue samples and various cut-offs were used to evaluate its immunohistochemical expression. HIF-1α expression in OSCC samples was significantly higher than in controls, with minimal immunoreactivity in NOM. HIF-1α overexpression was significantly associated with increased tumor size (p = 0.046). However, no association was found between HIF-1α overexpression and increasing Broder's histological grade or TNM stage. The cut-off >10% cells with moderate to marked intensity carried a sensitivity of 70% and a specificity of 100% to distinguish between tumor and control. ROC curve analysis of HIF-1α weighted histoscores showedHIF-1α overexpression as a highly sensitive and specific diagnostic test (p < 0.001, AUC = 0.833). HIF-1α overexpression is a tumor-specific finding associated with increased tumor size and carries a potential diagnostic role.
ABSTRACT
BACKGROUND: Oral squamous cell carcinoma (OSCC) may arise from premalignant oral lesions (PMOL) in most cases. Minichromosome maintenance 3 (MCM3) is a proliferative marker that has been investigated as a potential diagnostic biomarker in the diagnosis of oral cancer. OBJECTIVES: To evaluate the association of MCM3 expression, its clinicopathologic parameters and to identify snuff (also called naswar) as a potential risk factor for changes in MCM3 expression in PMOL and OSCC. METHODOLOGY: Immunohistochemistry (IHC) of MCM3 was performed on 32 PMOL, 32 OSCC and 16 normal controls after optimization of IHC methodology. Histoscore (0-300) was used as a scoring system and seven different cut-offs were identified for analyses. Data were analyzed using various statistical tests. RESULTS: Among the seven cutoffs, 40% strong positive cells were found to be a better cut-off as they were associated with many pathological variables (Broder's grade, Aneroth's grade, and mitotic activity). The differential MCM3 expression in oral lesions (PMOL and OSCC) was statistically significant (p = 0.03). Moreover, MCM3 expression is raised with increased duration and frequency of snuff use. CONCLUSION: High MCM3 expression is associated with disease progression and is a potential indicator of malignant transformations from PMOL to OSCC. Moreover, the use of snuff is associated with MCM3 over-expression.
