Microsatellite instability and loss of heterozygosity have distinct prognostic value for testicular germ cell tumor recurrence

Velasco, A; Riquelme E.; Schultz M.; Wistuba, II; Villarroel L.; Koh, MS; Leach, FS

Abstract

Germ cell tumor (GCT) is the most common genitourinary malignancy of men between the ages of 18 and 35 years. Therapy is ultimately successful in over 90% of patients, however significant morbidity and mortality can be associated with adjuvant treatment and relapse. Molecular markers that predict treatment response and/or poor outcome would have immediate clinical benefit since adjuvant treatment could be selectively reserved for patients at higher risk for relapse and those patients most likely to respond to treatment. In order to identify potential prognostic molecular markers, we evaluated 118 GCT for microsatellite instability (MSI), loss of heterozygosity (LOH) and MSH2 immunostaining to identify tumors associated with relapse and/or poor outcome following initial surgical, medical and/or radiation therapy. MSI in 3 or more markers and/or low MSH2 staining were associated with relapse while LOH in the absence of MSI and/or high MSH2 staining were not. Twenty-five percent of GCT exhibited genetic instability in 3 or more microsatellite markers (MSI+ tumors), 15% exhibited LOH in the absence of MSI (LOH only tumors) and 44% exhibited decreased or absent MSH2 immunostaining (low MSH2 staining tumors). Thirty-six patients (30%) relapsed and 27 of these patients (75%) had MSI+ and/or low MSH2 staining tumors. Only one patient (3%) with an LOH only tumor and no patients with high MSH2 staining and LOH only tumors relapsed. Therefore distinct GCT subpopulations identified by detection of MSI, LOH and MMR expression are associated with different clinical outcomes. MMR deficient testicular GCT with increased frequency of MSI had an increased association with tumor recurrence compared to GCT with an intact MMR system and LOH in the absence of MSI. ©2004 Landes Bioscience.

Más información

Título según WOS: Microsatellite instability and loss of heterozygosity have distinct prognostic value for testicular germ cell tumor recurrence
Título según SCOPUS: Microsatellite instability and loss of heterozygosity have distinct prognostic value for testicular germ cell tumor recurrence
Título de la Revista: CANCER BIOLOGY THERAPY
Volumen: 3
Número: 11
Editorial: Landes Bioscience
Fecha de publicación: 2004
Página de inicio: 1152
Página final: 1158
Idioma: English
Notas: ISI, SCOPUS