Expression of hMLH1 and hMSH2 and assessment of microsatellite instabilityin testicular and mediastinal germ cell tumours

The aim of this study was to investigate DNA mismatch repair deficiency in male germ cell tumours. We analysed the expression of two mismatch repair p roteins, human mutL homologue 1 (hMLH1) and human mutS homologue 2 (hMSH2), and evaluated the frequency of microsatellite instability with 10 mononucl eotide and two dinucleotide repeat sequences, in 39 paired tumour/normal DN A samples obtained from 17 testicular and two mediastinal germ cell tumours . In all 19 cases, hMLH1 and hMSH2 both showed nuclear immunolocalization i n invasive and testicular in-situ tumours. In non-neoplastic seminiferous t ubules, hMLH1 was expressed only in premeiotic germ cells, while hMSH2 was seen in all stages of spermatogenesis. Genetic analysis of dinucleotide mar kers revealed loss of heterozygosity in one of two testicular yolk sac tumo urs at D18S58 and an allelic shift at D2S123 in two of three testicular emb ryonal carcinomas, while none of the 12 seminomas exhibited a genetic abnor mality at these loci. No abnormalities were demonstrated with the 10 mononu cleotide markers. The two mediastinal germ cell tumours showed no genetic i nstability or allelic loss with all 12 markers. We suggest that genetic alt erations as assessed by microsatellite analysis in germ cell tumours; may r eflect tissue maturation and phenotypic differentiation rather than tumour progression. In addition, we suggest that hMLH1 and hMSH2 genes may not be implicated in the genesis of germ cell tumours.