title: Expression of hMLH1 and hMSH2 and assessment of microsatellite instability in testicular and mediastinal germ cell tumours.
abstract: 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.
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Devouassoux-Shisheboran
authors.forename: C
authors.initials: C
authors.lastname: Mauduit
authors.forename: R
authors.initials: R
authors.lastname: Bouvier
authors.forename: F
authors.initials: F
authors.lastname: Berger
authors.forename: M
authors.initials: M
authors.lastname: Bouras
authors.forename: J P
authors.initials: JP
authors.lastname: Droz
authors.forename: M
authors.initials: M
authors.lastname: Benahmed
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D020137:Base Pair Mismatch / Q000235:genetics; D002352:Carrier Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018240:Endodermal Sinus Tumor / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018237:Germinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein