The diagnosis and management of uterine smooth muscle tumors with uncertain malignant potential (STUMP) is often challenging, and genomic data on these lesions as well as on uterine smooth muscle lesions are limited. We tested the hypothesis that genomic profile determination by array-CGH could split STUMP into a benign group with scarce chromosomal alterations akin to leiomyoma and a malignant group with high chromosomal instability akin to leiomyosarcoma. Array-CGH genomic profile analysis was conducted for a series of 29 cases of uterine STUMP. A group of ten uterine leiomyomas and ten uterine leiomyosarcomas served as controls. The mean age was 50 years (range, 24-85) and the follow-up ranged from 12 to 156 months (average 70 months). Since STUMP is a heterogenous group of tumors with genomic profiles that can harbor few to many chromosomal alterations, we compared genomic indices in leiomyomas and leiomyosarcomas and set a genomic index=10 threshold. Tumors with a genomic index <10 were classified as nonrecurring STUMPs and those with a genomic index >10 represented STUMPs with recurrences and unfavorable outcomes. Hence, the genomic index threshold splits the STUMP category into two groups of tumors with different outcomes: a group comparable to leiomyomas and another similar to leiomyosarcomas, but more indolent. In our STUMP series, genomic analysis by array-CGH is an innovative diagnostic tool for problematic smooth muscle uterine lesions, complementary to the morphological evaluation approach. We provide an improved classification method for distinguishing truly malignant tumors from benign lesions within the category of STUMP, especially those with equivocal morphological features.

] Department of Biopathology Institut Bergonié Comprehensive Cancer Centre Bordeaux France [2] Institut National de la Santé et de la Recherche Medicale U916 Bordeaux France

Department of Biopathology Institut Bergonié Comprehensive Cancer Centre Bordeaux France

Department of Medical Oncology Institut Bergonié Comprehensive Cancer Centre Bordeaux France

Department of Oncology Gynaecologic Oncology KU Leuven University of Leuven Department of Obstetrics and Gynaecology University Hospitals Leuven Leuven Belgium

Department of Pathology Centre Alexis Vautrin Comprehensive Cancer Centre Vandoeuvre les Nancy France

Department of Pathology Centre Jean Perrin Comprehensive Cancer Centre Clermont Ferrand France

Department of Pathology Centre JF Leclerc Comprehensive Cancer Centre Dijon France

Department of Pathology Centre Oscar Lambret Comprehensive Cancer Centre Lille France

Department of Pathology Clinic of Gynecopathology and Senology Erasme University Hospital Bruxelles Belgium

Department of Pathology Hôpital de la Croix Rousse Lyon France

Department of Pathology ICO Paul Papin Comprehensive Cancer Centre Angers France

Department of Pathology Institut Gustave Roussy Comprehensive Cancer Centre Villejuif France

Department of Pathology University Hospital Montpellier France

Department of Surgery Institut Bergonié Comprehensive Cancer Centre Bordeaux France

Gynaecological Oncology Center Department of Obstetrics and Gynaecology Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Prague Czech Republic

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Genome profiling is an efficient tool to avoid the STUMP classification of uterine smooth muscle lesions: a comprehensive array-genomic hybridization analysis of 77 tumors