A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer

To clarify the mechanism of acquired CDDP resistance in ovarian cancer, we compared the microsatellite instability (MSI) by the amplification of 10 mi crosatellite loci and immunohistochemical detection of hMSH2 and hMLH1 expr ession between the primary resected tumours and the secondary resected resi dual tumours after 5 or 6 courses of CDDP-based chemotherapy in the 24 case s of ovarian cancer. Of the 24 primary resected tumours, 9 (37.5%) showed M SI (7 cases of MSI-L, 2 cases of MSI-H), while 15 (72.5%) were microsatelli te stable tumours (MSS). The primary tumours also had MSI in the residual t umours after CDDP-based chemotherapy. However, all of the cases with MSS in the primary resected tumours exhibited MSI (2 cases were MSI-L, and 13 cas es were MSI-H) in the residual tumours after CDDP-based chemotherapy (P < 0 .001). Furthermore, 11 (73.3%) of these cases which changed from MSS to MSI also had a change in the expression of hMLH1 from positive to undetectable (P < 0.001). Our data suggest that tumour MSI changes during CDDP-based ch emotherapy, and that the loss of hMLH1 expression is one of the factors tha t has the greatest effect on this transformation. (C) 2001 Cancer Research Campaign http://www.bjcancer.com.