Epidermal growth factor-induced cyclooxygenase-2 expression in oral squamous cell carcinoma cell lines is mediated through extracellular signal-regulated kinase 1/2 and p38 but is Src and nuclear factor-kappa B independent.

The intracellular signalling cascade(s) mediating epidermal growth factor (EGF)-induced cyclooxygenase-2 (COX-2) expression is poorly defined in oral carcinomas. Investigation of two different oral squamous cell carcinoma (OSCC) cell lines with high EGF-induced COX-2 expression revealed, however, that this expression was dependent on two mitogen-activated protein kinase (MAPK) pathways [extracellular signal-regulated kinase 1/2 (ERK1/2) and p38] because combined inhibition of these pathways was needed to abolish EGF-induced COX-2 expression. Surprisingly, inhibition of phosphoinositide-3 kinase (PI3K) increased EGF-induced COX-2 expression in the basaloid OSCC cell line (C12), suggesting a PI3K-controlled, inhibitory COX-2-regulating pathway. Neither the transcription factor nuclear factor-kappaB (NF-kappaB), nor Src, was involved in EGF-induced COX-2 expression. The results suggest that EGF-induced COX-2 expression is regulated by several pathways, and emphasizes that individual tumors use different strategies for intracellular signalling.

Basaloid squamous carcinoma of the oral cavity: report of 2 cases and study of AgNOR, PCNA, p53, and MMP expression.

Basaloid squamous carcinoma (BSC) is an uncommon aggressive variant of squamous cell carcinoma (SCC) with a predilection for the head and neck. In the English literature, approximately 40 cases of BSC in the oral cavity have been described. In this study, the clinicopathologic features of 2 cases of BSC affecting the buccal mucosa are reported. In addition, we compare the proliferative and invasive potential of BSC cells with that of poorly differentiated SCC cells matched for age, sex, site, and TNM status. Proliferative activity was studied through use of the argyrophilic nuclear organizer region (AgNOR) method and immunohistochemical quantification of proliferating cell nuclear antigen (PCNA). The invasive potential was evaluated through use of the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for matrix metalloproteinases (MMPs). Alterations of p53 were also investigated through use of immunohistochemistry. The tumors showed many clinical and histopathologic similarities to tumors in cases previously reported. The AgNOR and PCNA indices were significantly higher in the 2 cases of BSC than in the cases of SCC. Immunostaining for p53 protein showed a higher percentage of positive cells and more intense staining in the BSC tissues than in the SCC tissues. RT-PCR studies clearly demonstrated that the expression of MMP-1, MMP-2, and MMP-9 was higher in cells from BSCs than in cells from SCCs. Taken together, the data described here are compatible with the concept that BSC has a more aggressive biologic behavior than conventional SCC.