Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

Abstract

Objective Endometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS) are the two most common uterine sarcomas, but both are rare tumors. The aim of the present study was to compare the global gene expression patterns of ESS and LMS. Methods Gene expression profiles of 7 ESS and 13 LMS were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Results Unsupervised hierarchical clustering using all 54,675 genes in the array separated ESS from LMS samples. We identified 549 unique probes that were significantly differentially expressed in the two malignancies by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini–Hochberg correction, of which 336 and 213 were overexpressed in ESS and LMS, respectively. Genes overexpressed in ESS included SLC7A10, EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1 and GCGR. Genes overexpressed in LMS included CDKN2A, FABP3, TAGLN, JPH2, GEM, NAV2 and RAB23. The top 100 genes overexpressed in LMS included those coding for myosin light chain and caldesmon, but not the genes coding for desmin or actin. CD10 was not overexpressed in ESS. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry. Conclusions We present the first study in which gene expression profiling was shown to distinguish between ESS and LMS. The molecular signatures unique to each of these malignancies may aid in expanding the diagnostic battery for their differentiation, and may provide a molecular basis for prognostic studies and therapeutic target discovery.

Gynecologic Cancer InterGroup (GCIG) Consensus Review

“…Genetic profiling is investigational in LMS, but could potentially elucidate treatment targets. 16,17 Genetic profiling may be able to improve prognostication by identifying gene signatures that differentiate indolent uterine LMS tumors from clinically aggressive tumors (J. Barlin and D. Levine, personal communication, July 2014).…”

Immunohistochemical panel to differentiate endometrial stromal sarcoma, uterine leiomyosarcoma and leiomyoma: something old and something new

“…New immunomarkers are thus needed to face this challenging problem 21. Novel gene expression signatures differentiating ESS from ULMS, conducted by Davidson et al ,22 have recently emerged. The authors found that genes that were overexpressed in ESS were: SLCA7A10/ASC1 , EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1 and GCGR.…”

“…Genes that were overexpressed in ULMS were : CDKN2A, FABP3 , TAGLN, JPH2, GEM, NAV2 and RAB23. 22 Of all of these proteins, transgelin (TAGLN) was the only antibody shown in a small number of uterine sarcomas and soft tissue sarcomas to have promising results 23 24…”

Malignant tumors of the uterine corpus: molecular background of their origin

“…On the other side, CD10 was not overexpressed in endometrial stromal sarcoma. This is even used as a marker of endometrial neoplasms [61].…”

“…Davidson et al [61] discovered further genes overexpressed in primary uterine leiomyosarcomas including OSTN, NLGN4X, NLGN1, SLITRK4, MASP1, XRN2, ASS1, RORB, HRASLS, and TSPAN7. They also found out different genes overexpressed in metastases of leiomyosarcomas including TNNT1, FOLR3, TDO2, CRYM, GJA1, TSPAN10, THBS1, SGK1, SHMT1, EGR2, and AGT.…”