The diagnosis of a uterine smooth muscle lesion is, in the majority of cases, straightforward. However, in a small number of cases, the morphological criteria used in such lesions cannot differentiate with certainty a benign from a malignant lesion and a diagnosis of smooth muscle tumor with uncertain malignant potential (STUMP) is made. Uterine leiomyosarcomas are often easy to diagnose but it is difficult or even impossible to identify a prognostic factor at the moment of the diagnosis with the exception of the stage. We hypothesize, for uterine smooth muscle lesions, that there is a gradient of genomic complexity that correlates to outcome. We first tested this hypothesis on STUMP lesions in a previous study and demonstrated that this 'gray category' could be split according to genomic index into two groups. A benign group, with a low to moderate alteration rate without recurrence and a malignant group, with a highly rearranged profile akin to uterine leiomyosarcomas. Here, we analyzed a large series of 77 uterine smooth muscle lesions (from 76 patients) morphologically classified as 19 leiomyomas, 14 STUMP and 44 leiomyosarcomas with clinicopathological and genomic correlations. We confirmed that genomic index with a cut-off=10 is a predictor of recurrence (P<0.0001) and with a cut-off=35 is a marker for poor overall survival (P=0.035). For the tumors confined to the uterus, stage as a prognostic factor was not useful in survival prediction. At stage I, among the tumors reclassified as molecular leiomyosarcomas (ie, genomic index ≥10), the poor prognostic markers were: 5p gain (overall survival P=0.0008), genomic index at cut-off=35 (overall survival P=0.0193), 13p loss including RB1 (overall survival P=0.0096) and 17p gain including MYOCD gain (overall survival P=0.0425). Based on these findings (and the feasibility of genomic profiling by array-comparative genomic hybridization), genomic index, 5p and 17p gains prognostic value could be evaluated in future prospective chemotherapy trials.

Argot Lab Lausanne Switzerland

Centre for Gynecologic Oncology Amsterdam Antoni Van Leeuwenhoek Netherlands Cancer Institute Amsterdam The Netherlands

Department of Biopathology Institut Bergonié Comprehensive Cancer Centre Bordeaux France

Department of Medical Oncology Institut Bergonié Comprehensive Cancer Centre Bordeaux France

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 Brussels Belgium

Department of Pathology Hôpital Universitaire Lyon Sud Pierre Benite France

Department of Pathology ICO Site Paul Papin Comprehensive Cancer Centre Angers France

Department of Pathology Institut Gustave Roussy Comprehensive Cancer Centre Villejuif France

Department of Pathology University Hospital Poitiers 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 Czech Republic

Institut National de la Santé et de la Recherche Medicale U1218 Bordeaux France

Institut Universitaire de Pathologie Lausanne Switzerland

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

Oncology Department Centre Antoine Lacassagne Comprehensive Cancer Centre Nice France

Oncology Department Centre Oscar Lambret Comprehensive Cancer Centre Lille France

University of Bordeaux Bordeaux France

See more in PubMed

Am J Surg Pathol. 1997 Nov;21(11):1261-70 PubMed

J Clin Oncol. 1985 Sep;3(9):1240-5 PubMed

Int J Gynecol Cancer. 2015 May;25(4):622-8 PubMed

Am J Surg Pathol. 2013 May;37(5):650-8 PubMed

Am J Pathol. 1998 Sep;153(3):985-90 PubMed

Gynecol Oncol. 2009 Mar;112(3):563-7 PubMed

Lancet Oncol. 2009 Dec;10(12):1188-98 PubMed

Mod Pathol. 2016 Jan;29 Suppl 1:S104-20 PubMed

Mod Pathol. 2016 Oct;29(10 ):1262-77 PubMed

Am J Surg Pathol. 1994 Jun;18(6):535-58 PubMed

Cancer. 2012 Feb 1;118(3):660-9 PubMed

Cancer. 2014 Oct 15;120(20):3165-77 PubMed

Genes Chromosomes Cancer. 2016 Feb;55(2):124-30 PubMed

Int J Gynecol Cancer. 2009 Apr;19(3):385-90 PubMed

Mod Pathol. 2014 Jun;27(6):840-50 PubMed

Cancer Genet Cytogenet. 2006 Sep;169(2):94-101 PubMed

Eur J Cancer. 2008 Apr;44(6):808-18 PubMed

N Engl J Med. 2013 Nov 28;369(22):2160-1 PubMed

Mod Pathol. 2015 Jul;28(7):1001-10 PubMed

N Engl J Med. 2013 Jul 4;369(1):43-53 PubMed

Int J Oncol. 2008 May;32(5):1111-7 PubMed

Genes Chromosomes Cancer. 2001 Jun;31(2):117-24 PubMed

Clin Cancer Res. 2012 Feb 1;18(3):826-38 PubMed

Am J Obstet Gynecol. 1987 Mar;156(3):660-2 PubMed

Cancer. 2013 May 15;119(10):1816-22 PubMed

Acta Obstet Gynecol Scand. 2016 Sep;95(9):984-90 PubMed

Acta Oncol. 1995;34(6):797-802 PubMed

Am J Clin Pathol. 2016 Apr;145(4):449-58 PubMed

Cancer Res. 2009 Mar 15;69(6):2269-78 PubMed

Gynecol Oncol. 2017 Apr;145(1):208-216 PubMed

Cancer. 2000 Mar 15;88(6):1425-31 PubMed

Am J Clin Oncol. 1995 Aug;18(4):282-6 PubMed

Am J Surg Pathol. 2014 Oct;38(10):1330-9 PubMed

Am J Obstet Gynecol. 2003 Jan;188(1):100-7 PubMed

PLoS Genet. 2016 Feb 18;12(2):e1005850 PubMed

Sarcoma. 2015;2015:704124 PubMed

Cancer Res. 2010 Jan 15;70(2):501-11 PubMed

Am J Surg Pathol. 2011 Apr;35(4):522-9 PubMed

Immunohistochemical and selected genetic reflex testing of all uterine leiomyosarcomas and STUMPs for ALK gene rearrangement may provide an effective screening tool in identifying uterine ALK-rearranged mesenchymal tumors