Transforming growth factor-beta isoform expression in human ovarian tumours

The expression patterns of members of the transforming growth factor-beta (TGF-beta) family were analysed in 96 primary ovarian tumours by RNAse protection assay. mRNA for the three mammalian isoforms, TGF-beta 1, TGF-beta 2 and TGF-beta 3, was detected in 46, 66 and 66% of 74 malignant tumours, respectively, with the predominant patterns of expression being either dual or triple co-expression. TGF-beta II receptor expression, detected by reverse-transcription PCR, was present in 92% malignant tumours. Expression patterns were similar between malignant, borderline and benign tumours, although TGF-beta 1 incidence was reduced in benign tumours. In malignant tumours, the incidence of TGF-beta 1 expression was less than that of either TGF-beta 2 (P = 0.02) or TGF-beta 3 (P = 0.0014), while in both malignant and borderline tumours, TGF-beta 2 and TGF-beta 3 tended to be co-expressed. Aneuploid tumours were more likely than diploid tumours to express multiple rather than single forms of TGF-beta (P = 0.018). The incidence of TGF-beta 1 expression was reduced in PR-moderate/rich (PR > 20 fmol/mg protein) relative to PR-negative/poor tumours (P = 0.048), while TGF-beta 3 expression was increased in ER-moderate/rich (ER > 20 fmol/mg protein) tumours compared to ER-negative/poor tumours (P = 0.0012). Expression of TGF-beta 3, but not TGF-beta 1 or TGF-beta 2, was associated with advanced stage disease (P = 0.014) and, in the malignant group, reduced survival (P = 0.02) with a hazard ratio of 2.6. These data suggest a possible role for TGF-beta 3 in the progression of ovarian cancer.