Overexpression of osteopontin in clear cell carcinoma of the ovary: close association with HNF-1beta expression

Abstract

Aims: Transcription factor hepatocyte nuclear factor (HNF)-1beta is selectively expressed in clear cell carcinoma (CCC) of the ovary. One of the potential HNF-1beta target genes is osteopontin (OPN). Although elevation of OPN mRNA has been reported in CCC, it remains unclear whether CCC cells overexpress OPN protein. The aim was to investigate the expression of OPN protein and its correlation with HNF-1beta status in CCC.

Methods and results: Three CCC and two serous adenocarcinoma (SA) cell lines were evaluated for expression of OPN by reverse transcriptase-polymerase chain reaction and immunocytochemistry. OPN expression, at both the mRNA and protein levels, was higher in the three CCCs than in the two SAs. HNF-1beta expression was detected in the CCCs but not in the SAs. Subsequently, 60 surgical specimens (30 CCCs and 30 SAs) were examined immunohistochemically for expression of OPN and HNF-1beta. All 30 CCCs showed immunopositivity for both OPN and HNF-1beta. The 12 (40%) CCCs with a high OPN score all had a high HNF-1beta score. In contrast, SAs rarely showed immunoreactivity for OPN or HNF-1beta.

Conclusions: OPN expression is elevated in ovarian CCC and is closely associated with HNF-1beta overexpression. HNF-1beta is likely to participate in OPN up-regulation in CCC.