Gene Expression Signatures Differentiate Uterine Leiomyosarcoma and Endometrial Stromal Sarcoma
Ben Davidson, Vera Abeler, Ellen Hellesylt, Arild Holth, Ie-Ming Shih, Gunnar B Kristensen, Tone Skeie-Jensen, Yanqin Yang, Tian-Li Wang. Norwegian Radium Hospital, Oslo, Norway; Johns Hopkins Medical Institutions, Baltimore, MD; National Institutes of Health, Bethesda, MD
Background: Leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS) are the two most common uterine sarcomas, but both are rare cancers. The aim of the present study was to compare the global gene expression patterns of LMS and ESS, in order to expand and improve the panel of biomarkers currently available for their diagnosis, as well as to define type-specific biological targets.
Design: 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 cancers 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, IGDCC3, EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1 and GCGR. Genes overexpressed in LMS included CDKN2A, FABP3, TAGLN, JPH2, GEM, NAV2, RAB23. The top 100 differentiators for each entity included the MYLK and CALD1 genes, coding for myosin light chain and caldesmon, respectively, both overexpressed in LMS, but not the genes coding for CD10, desmin or actin. 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 cancers may aid in expanding the diagnostic battery for their differentiation, and may provide a molecular basis for prognostic studies and therapeutic target discovery.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 135, Tuesday Afternoon