Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

KAI1, a metastasis suppressor gene: a potential prognostic marker in prostate cancer?

M Lijovic BSc, AG Frauman MD

Clinical Pharmacology and Therapeutics Unit, Dept Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Melbourne, Australia,

More sensitive prognostic markers in primary prostate cancer (CaP) are needed since current diagnostic methods cannot accurately predict individual patient outcome or determine which patients are at highest risk of metastases. Thus, biological markers indicating likely metastatic behavior would be clinically useful. The KAI1 metastasis suppressor gene is an attractive candidate, following findings of an inverse correlation between KAI1 expression and clinical metastatic behavior of CaP. AIMS: To determine the functional and clinical significance of KAI1 in the development and progression of primary CaP, at a gene and protein level. METHODS: (i) RT-PCR and (ii) immunohistochemistry (using a polyclonal anti-human KAI1 antibody; Santa Cruz Biotechnology), with antigen retrieval by microwave treatment in citric acid buffer, was performed on formalin-fixed, paraffin-embedded primary CaP specimens. RESULTS: A biphasic pattern of KAI1 mRNA expression in primary CaP was observed, compared to hyperplasic or normal prostate controls (n=6). A significant elevation of KAI1 mRNA in low grade tumours (Gleason grade 2-6; n=13) and a reduction in high grade tumours (Gleason grade 7-10; n=16) was seen (p<0.001, one way ANOVA). Immunohistochemical studies in low grade CaP (n=12) and high grade CaP (n=10) demonstrated localization of KAI1 in prostatic epithelial cells and mirrored the mRNA findings. Thus, increased KAI1 levels are seen in well differentiated tumours and reduced levels are seen in poorly differentiated tumours, compared to surrounding normal or hyperplastic prostate. CONCLUSIONS: Our data suggest the possibility that KAI1 overexpression plays a restraining role early in primary CaP progression, with loss of constraint leading to more aggressive cancer behavior. Altered KAI1 expression may therefore be predictive of metastatic CaP, though correlation of findings with clinical outcomes is needed.

KEY WORDS: prognostic marker, prostate cancer, metastasis suppressor gene, metastasis.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on prognostic markers.