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Thrombospondin-1 and -2 Messenger RNA Expression in Invasive Cervical Cancer

Correlation with Angiogenesis and Prognosis

Department of Obstetrics and Gynecology [J. K., I. H., N. S., A. H., M. Y., T. K.] and Faculty of Health Sciences [H. O.], Okayama University Medical School, Okayama 700-8558, Japan

Purpose: TSP association with clinicopathological features, including microvessel count, regarding prognostic significance was examined in patients presenting with invasive cervical cancer.

Experimental Design: Gene expression of TSP-1 and TSP-2 was assessed by reverse transcription-PCR in 10 normal cervix and 78 invasive cervical cancer samples.

Results: TSP-1 and TSP-2 mRNA expression was detected in seven (70.0%) of the normal cervical specimens. TSP-2 mRNA expression in normal cervix was significantly higher than that in cases involving cervical cancer (P = 0.032). TSP-1 mRNA expression was significantly lower in tumors characterized by advanced stage (P = 0.047). Fifty-three patients displaying stage Ib-IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. Expression of TSP-1 and TSP-2 mRNA was significantly lower in tumors exhibiting parametrial invasion (P = 0.016 and P = 0.049, respectively). Microvessel counts were significantly higher when decreased TSP-1 expression was evident (P = 0.029). The microvessel count in patients lacking TSP-2 mRNA expression was higher than that observed in patients displaying TSP-2 mRNA expression, although it was not statistically significant (P = 0.062). Subjects demonstrating TSP-1 mRNA expression exhibited significantly better prognosis than those lacking TSP-1 mRNA expression (P = 0.0038). Furthermore, TSP-1 mRNA expression was an independent prognostic factor in the multivariate analysis.

Conclusions: These findings provide evidence that TSP-1 expression is of value as a prognostic factor in cervical cancer. The inverse correlation between TSP expression and microvessel count also indicates that decreased TSP expression may be associated with an angiogenic phenotype in this class of neoplasm.

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