Head and neck squamous cell carcinoma in non-smoking and non-drinking patients with multiple tumors: etiologic significance of p53 and Ki-67 in non-tumorous epithelium

BACKGROUND: Non-smoking and non-drinking patients with head and neck squamous cell carcinoma have different clinical characteristics than their smoking and drinking counterparts. They are predominantly older female patients with oral cavity tumors, however, both groups show the same percentage of second primary tumors. Expression of tumor suppressor gene p53 and proliferation marker Ki-67 in mucosal epithelial cells was analyzed to study whether biomarker expression is associated with a history of smoking and drinking and with single and multiple tumors. METHODS: Non-smoking and non-drinking patients with multiple (n = 18) and single tumors (n = 15), smoking and drinking patients with multiple (n = 15) and single tumors (n = 14) were selected. For all groups, p53 and Ki-67 expression patterns in non-tumorous (tumor-adjacent) mucosa including positivity of dispersed single cells and clusters for p53 and for suprabasal expression of Ki-67 were immunohistochemically analyzed and compared. RESULTS: p53 expression was significantly higher in users of tobacco and alcohol than in non-users. Ki-67 expression was not affected by tobacco and alcohol usage. Both Ki-67 and p53 were similarly expressed in the groups with single and multiple tumors and hence not significantly related to the number of tumors. CONCLUSIONS: Non-smoking and non-drinking patients with squamous cell carcinoma have the same risk for developing multiple tumors as their smoking and drinking counterparts. As this occurs without an increased expression of p53 or Ki-67, the significance of these proteins as biomarkers indicating pre-malignant mucosal alterations is doubtful. Further research is needed to clarify this predisposition for developing multiple head and neck cancer.