Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

ETS-1 expression in human oral squamous cell carcinoma: Potential prognostic implications

P Pande MSc 1, N Chakravarti MSc 1, S Soni MSc 1, M Mathur MD 2, NK Shukla MS 3, R Ralhan PhD 4

1 Dept Biochemistry, 2 Dept Pathology © Surgical Oncology Unit, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India,

AIM: In oral squamous cell carcinoma (SCC), the presence of lymph node metastasis is one of the most important prognostic factors, correlating locoregional spread, recurrence, distant organ metastasis and survival. However, the biological factors implicated and the mechanisms underlying these events are not completely elucidated. Recently, we reported Ets-1 expression in oral SCC and proposed that it may serve as a plausible marker of invasive potential and lymph node metastasis (Pande et al. J Pathol 1999 Sep; 189(1):40-45). Herein, we investigated the prognostic significance of Ets-1 expression in oral cancer. METHODS: Ets-1 immunoreactivity was detected in tissue sections of untreated oral SCCs(90 case enrolled in IRCH, AIIMS), by immunohistochemical analysis. Ets-1 mRNA expression was detected in these sections by in situ hybridization. The role of Ets-1 in tumor invasion and metastasis was investigated by transiently transfecting Stromelysin (a matrix metalloproteinase carrying Ets-1 responsive element in its promoter), in human oral cancer cell line. RESULTS: Ets-1 overexpression was observed in 62% of oral SCCs and was found to be significantly associated with tumor stage, lymph node involvement and distant organ metastasis. Kaplan Meier survival analysis entailed significant association of Ets-1 expression with reduced disease free survival in oral SCCs(p=0.0041). Further, in vitro transactivation of stromelysin promoter in oral cancer cells was observed by Ets-1. CONCLUSION: These findings underscore the role of Ets-1 in oral tumor invasion and metastasis, suggesting the utility of Ets-1 as a prognosticator for oral cancer.

KEY WORDS: Ets-1, Prognosticator, Oral cancer.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on prognostic markers.