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

被引:48
作者
Croce, Sabrina [1 ,2 ]
Ducoulombier, Agnes [3 ,4 ]
Ribeiro, Agnes [1 ]
Lesluyes, Tom [2 ,5 ]
Noel, Jean-Christophe [6 ]
Amant, Frederic [7 ,8 ,9 ]
Guillou, Louis [10 ,11 ]
Stoeckle, Eberhard [12 ]
Devouassoux-Shisheboran, Mojgan [13 ]
Penel, Nicolas [3 ]
Floquet, Anne [14 ]
Arnould, Laurent [15 ]
Guyon, Frederic [12 ]
Mishellany, Florence [16 ]
Chakiba, Camille [14 ]
Cuppens, Tine [7 ,8 ]
Zikan, Michal [17 ,18 ]
Leroux, Agnes [19 ]
Frouin, Eric [20 ]
Farre, Isabelle [21 ]
Genestie, Catherine [22 ]
Valo, Isabelle [23 ]
MacGrogan, Gaetan [1 ]
Chibon, Frederic [1 ,2 ]
机构
[1] Inst Bergonie, Ctr Comprehens Canc, Dept Biopathol, Bordeaux, France
[2] INSERM, U1218, Bordeaux, France
[3] Ctr Oscar Lambret, Dept Oncol, Ctr Comprehens Canc, Lille, France
[4] Ctr Antoine Lacassagne, Ctr Comprehens Canc, Oncol Dept, Nice, France
[5] Univ Bordeaux, Bordeaux, France
[6] Erasme Univ Hosp, Dept Pathol, Clin Gynecopathol & Senol, Brussels, Belgium
[7] Univ Leuven, KU Leuven, Dept Oncol, Gynaecol Oncol, Leuven, Belgium
[8] Univ Hosp Leuven, Dept Obstet & Gynaecol, Leuven, Belgium
[9] Antoni Van Leeuwenhoek Netherlands Canc Inst, CGOA, Amsterdam, Netherlands
[10] Argot Lab, Lausanne, Switzerland
[11] Inst Univ Pathol, Lausanne, Switzerland
[12] Inst Bergonie, Ctr Comprehens Canc, Dept Surg, Bordeaux, France
[13] Hop Univ Lyon Sud, Dept Pathol, Pierre Benite, France
[14] Inst Bergonie, Ctr Comprehens Canc, Dept Med Oncol, Bordeaux, France
[15] Ctr JF Leclerc, Ctr Comprehens Canc, Dept Pathol, Dijon, France
[16] Ctr Jean Perrin, Ctr Comprehens Canc, Dept Pathol, Clermont Ferrand, France
[17] Charles Univ Prague, Fac Med 1, Dept Obstet & Gynaecol, Gynaecol Oncol Ctr, Prague, Czech Republic
[18] Gen Univ Hosp, Prague, Czech Republic
[19] Ctr Alexis Vautrin, Ctr Comprehens Canc, Dept Pathol, Vandoeuvre Les Nancy, France
[20] Univ Hosp, Dept Pathol, Poitiers, France
[21] Ctr Oscar Lambret, Ctr Comprehens Canc, Dept Pathol, Lille, France
[22] Inst Gustave Roussy, Ctr Comprehens Canc, Dept Pathol, Villejuif, France
[23] ICO Site Paul Papin, Ctr Comprehens Canc, Dept Pathol, Angers, France
关键词
STAGE-I; PROGNOSTIC-FACTORS; LEIOMYOSARCOMA; SARCOMAS; DIFFERENTIATION; LEIOMYOMAS; SURVIVAL; IMPACT; PROGRESSION; ADRIAMYCIN;
D O I
10.1038/modpathol.2017.185
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:816 / 828
页数:13
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