The Missing Kiss of Life: Transcriptional Activity of the Metastasis Suppressor Gene KiSS1 in Early Breast Cancer

Abstract

Background: KiSS-1 is a metastasis suppressor gene encoding a neuropeptide with potent antimetastatic activities in tumour cell lines. The transcriptional activity of the gene and its associations in resected breast cancer were analysed. Materials and Methods: Tumour messenger RNA (mRNA) of the KiSS1 exon I/II boundary was extracted from paraffin-embedded stage II or III node-positive breast adenocarcinomas of 272 women. KiSS1 mRNA was examined for associations with outcome, disease and molecular characteristics. Results: Only 8 out of 272 tumours (3%) yielded detectable KiSS1 mRNA levels. There was no evidence of correlation of KiSS1 transcription with the number of involved axillary nodes, grade, hormone receptor status or tumour size. Of women with increased KiSS1 mRNA tumour levels, 87.5% were postmenopausal, whereas only 48% were postmenopausal among patients without detectable KiSS1 mRNA (p=0.03). No association of KiSS1 transcription was found with transcription of the cell cycle-regulators HER2, VEGF, p53, BCL2, PAEP, or BIRC5. At a median follow-up of 62 months, there was no statistically significant difference between women harbouring KiSS1 mRNA-negative versus-positive tumours in terms of disease-free and overall survival (log-rank test p=0.54 and p=0.55, respectively). Conclusion: The metastasis suppressor gene KiSS1 is silenced in the vast majority of resected node-positive breast adenocarcinomas. These findings support the antimetastatic role of the gene and warrant its study as a prognostic marker and a therapeutic target.