Cyclooxygenase Isozymes in Oral Squamous Cell Carcinoma: A Real-Time RT-PCR Study with Clinic Pathological Correlations

Abstract

COX-2 expression in tumour cells has been associated with carcinogenesis in many human neoplasms, including head and neck cancer, while the COX-l isoform of the cyclooxygenase enzyme is constitutively expressed in normal tissues. We measured COX-l and COX-2 m-RNA expression in samples of both oral cancer and matched oral mucosa from 22 patients by RealTime RT-PCR; clinic pathological data (grading, TNM staging, inflammation, follow-up) of all patients were available for statistical evaluation. Most of the tumor samples in our study expressed at least one cyclooxygenase enzyme (COX-lor COX-2 mRNA) more than their matched normal oral mucosa (p<O.05), with no correlation with the entity of inflammation, and a significant inverse relationship was found between COX-l and COX-2 in each sample. Higher levels of COX-2 expression were associated with poor disease-free survival (p<O.05), but not with overall survival and higher tumor stage and grade. Our results suggest that COX-l may playa role in oral carcinogenesis, and could be regarded as a potential therapeutic target by chemo preventive drugs; moreover, COX-2 expression might be addressed as a new prognostic tool in the clinical management of OSCC.Among head and neck cancers, oral squamous cell carcinoma represents a distinct entity featuring a high incidence and mortality worldwide (I), despite the wide choice of available therapeutics (surgery, chemo and radiotherapy). Recent studies focus on the identification of new more specific drugs, on the basis of the unravelling of oral cancer pathogenesis. Several studies suggest that cyclooxygenase

Expression of cyclooxygenase-1 and cyclooxygenase-2 in normal and pathological human oral mucosa.

“…Our data are in agreement with all the studies [4,5,7,[23][24] that report a higher expression of COX-2 in precancerous lesions than in malignancies and that hypothesize a correlation between COX-2 activation and the early stages of carcinogenesis.…”

“…Moreover, opinions regarding the correlation between COX-2 expression and the histologic grade of oral cancer are highly conflicting; many authors report a progressive increase of COX-2 expression from normal oral mucosa towards invasive carcinoma [39,[41][42][43], others report an higher COX-2 expression in premalignant lesion than in malignancies [4,6,[44][45], while others report the lack of correlation between COX-2 level and tumor stage or grade [7,46].…”

“…Recently, over-expression of COX-2 was observed in a variety of human malignancies, including colonic, gastric, breast, esophageal, bronchial, prostatic carcinomas, and oral cancer [4][5][6][7][8][9][10]. Many studies indicated that COX-2 contributes to tumorigenesis and to the development of malignant phenotype through several mechanisms, such as (1) inhibition of apoptosis; (2) increased angiogenesis; (3) increased invasiveness; (4) modulation of inflammation/immuno-suppression; and (5) stimulation of cell proliferation [11][12][13].…”

Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer

“…Resection samples from 90 eligible mobile tongue SCC patients (47 males, 43 females) were analysed using a set of possible new and previously proposed immunohistochemical prognostic markers including microvessel density (CD31 and factor VIII), cyclooxygenase-2 (COX-2), the laminin-5 g2-chain, integrin avb6 and matrix metalloproteinases . The high expression levels of COX-2 are known to be associated with poor disease-free survival in oral squamous cell carcinoma (Pannone et al, 2007) and also laminin-5 g2-chain, a basement membrane protein (Gasparoni et al, 2007), and avb6 integrin, a transmembrane adhesion protein (Hynes, 1992) are known to be increased in invasive SCCs (Breuss et al, 1995;Jones et al, 1997;Ramos et al, 1997). Angiogenesis is crucial for tumour growth (Folkman et al, 1963) and metastasis (Folkman, 1990) but the role of angiogenesis is still controversial in oral SCC (Gasparini et al, 1993;Leedy et al, 1994;Hogmo et al, 1999;Macluskey et al, 2000) and thus deserves further investigation.…”

Update of prognostic and predictive biomarkers in oropharyngeal squamous cell carcinoma: a review

“…Pannone et al demonstrated in 22 patients with OSCC via real-time RT-PCR that a high COX-2 expression was associated with a worse DFS. A correlation with QS, tumor stage and grade could not be shown [85]. At this time, studies analyzing the relation of HPV status, COX-2 expression and clinicopathological parameters in OSCC still have not been done.…”