Yoko Harima MD, PhD, Presenter: Nothing to Disclose

Koshi Ikeda MD, PhD, Abstract Co-Author: Nothing to Disclose

Keita Utsunomiya MD, PhD, Abstract Co-Author: Nothing to Disclose

Atsushi Komemushi MD, PhD, Abstract Co-Author: Nothing to Disclose

Minoru Kamata MD, PhD, Abstract Co-Author: Nothing to Disclose

Satoshi Sawada MD, PhD, Abstract Co-Author: Nothing to Disclose

In a previous study to identify the set of genes related to radiosensitivity of advanced cervical carcinomas and to establish a predictive method, expression profiles of radiosensitive and radioresistant tumors were compared using a cDNA microarray analysis. Some of these genes had already been associated with radiation response, such as BAX, TEGT (BAX-inhibitor), XRCC5, PLAU, HIF1A, CD44, and TTK. In this series, to identify the most important gene related to prognosis after radiotherapy, we have validated these genes by mRNA expression from blinded 60 test patients using a real-time PCR.

A total of 60 patients with cervical cancer (4 Stage IIB, 47 Stage IIIB, and 9 Stage IVA) who underwent definitive radiotherapy between May 1995 and November 2005 were included in this study. We compared mRNA expression of 29 responder and 31 non-responder tumors after radiotherapy obtained by punch biopsy before treatment using a real-time PCR. Taqman probe was designed according to the sequence of BAX, TEGT, XRCC5, PLAU, HIF1A, CD44, and TTK cloned genes, with normalization to housekeeping genes. Differences in mRNA expression were analyzed using the Mann-Whitney U-test. The endpoint of this study was the correlation between mRNA expression and the overall survival rate of these patients according to Cox’s proportional-hazard model.

HIF1A and TTK mRNA expression values in non-responder group were higher than in responder group, however, not significantly (p = 0.079, p = 0.092, respectively). On univariate and multivariate analysis according to Cox’s proportional-hazard model, TTK was a statistically significant independent poor prognostic factor for overall survival rate after radiotherapy (HR, 1.06; 95% CI, 1.0-1.12, p=0.044, and HR, 1.35; 95% CI, 1.02-1.78, p=0.035).

The relatively high incidence of TTK may explain, at least in part, the poor prognosis of advanced cervical carcinomas after radiotherapy. These results may contribute knowledge for the development of new drug strategies for advanced cervical cancer.

The promise of TTK mRNA expression using a real-time PCR method lies in its potential for improving clinical strategies for treatment in advanced cervical carcinoma after radiotherapy.

Harima, Y, Ikeda, K, Utsunomiya, K, Komemushi, A, Kamata, M, Sawada, S, Prediction of Prognosis of Advanced Cervical Cancers after Radiotherapy by Real-time PCR.  Radiological Society of North America 2009 Scientific Assembly and Annual Meeting, November 29 - December 4, 2009 ,Chicago IL. http://archive.rsna.org/2009/8003050.html