Molecular Human Reproduction, Vol. 7, No. 12, 1099-1105,
December 2001
© 2001 European Society of Human Reproduction and Embryology
Testis and spermatogenesis |
Expression of hMLH1 and hMSH2 and assessment of microsatellite instability in testicular and mediastinal germ cell tumours
1 Institut National de la Santé et de la recherche Médicale, INSERM U-407, Communication en Biologie de la Reproduction, Faculté de médecine Lyon-Sud, B.P. 12, F-69921 Oullins Cedex, 2 Service d'Anatomie et de Cytologie Pathologiques, Hôpital de la Croix Rousse (Université Claude Bernard, Lyon I), 103 Grande rue de la Croix Rousse, 69317 Lyon, Cedex 04, 3 Service d'Anatomie et de Cytologie Pathologiques, Hôpital Edouard Herriot, 3, Place d'Arsonval, 69437 Lyon, Cedex 03, 4 Service d'Anatomie Pathologique, JE 2267, Centre hospitalier Lyon-Sud, 69495 Pierre Bénite Cedex and 5 Centre Léon Bérard, 28, rue Laennec, 69008 Lyon, France
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 proteins, human mutL homologue 1 (hMLH1) and human mutS homologue 2 (hMSH2), and evaluated the frequency of microsatellite instability with 10 mononucleotide and two dinucleotide repeat sequences, in 39 paired tumour/normal DNA samples obtained from 17 testicular and two mediastinal germ cell tumours. In all 19 cases, hMLH1 and hMSH2 both showed nuclear immunolocalization in invasive and testicular in-situ tumours. In non-neoplastic seminiferous tubules, hMLH1 was expressed only in premeiotic germ cells, while hMSH2 was seen in all stages of spermatogenesis. Genetic analysis of dinucleotide markers revealed loss of heterozygosity in one of two testicular yolk sac tumours at D18S58 and an allelic shift at D2S123 in two of three testicular embryonal carcinomas, while none of the 12 seminomas exhibited a genetic abnormality at these loci. No abnormalities were demonstrated with the 10 mononucleotide markers. The two mediastinal germ cell tumours showed no genetic instability or allelic loss with all 12 markers. We suggest that genetic alterations as assessed by microsatellite analysis in germ cell tumours may reflect 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.
germ cell tumour/hMLH1/hMSH2/microsatellite instability/testis
3 To whom correspondence should be addressed at: Institut National de la Santé et de la recherche Médicale, INSERM U-407, Communication en Biologie de la Reproduction, Faculté de médecine Lyon-Sud, B.P. 12, F-69921 Oullins Cedex, France. E-mail: benahmed{at}lsgrisn1.univ-lyon1.fr
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