[1145] Array Comparative Genomic Hybridization and Fluorescence In Situ Hybridization Analysis of Endometrial Carcinoma Specimens.

Jesse S Voss, Benjamin R Kipp, Lisa M Peterson, Fabiola Medeiros, Michael B Campion, Ekaterina Pestova, Kristine B Jacobson, Mona S Legator, Amy C Clayton, Kevin C Halling. Mayo Clinic, Rochester, MN; Abbott Molecular Inc., Des Plaines, IL

Background: Endometrial cancer (EC) is the most common female genital tract cancer in the United States. The goal of this study was to determine the frequency of chromosomal gains and losses by array comparative genomic hybridization (CGH) in EC and whether fluorescence in situ hybridization (FISH) can detect these abnormalities in paraffin-embedded EC specimens.
Design: Specimens were collected from 109 patients undergoing hysterectomy from 2005-2007. Forty specimens were analyzed by CGH with the Genosensor assay (Abbott Molecular Inc., Des Plaines, IL), 36 were analyzed by FISH and 33 by both methods. The study comprised 61 endometrioid (EM) carcinomas (32 grade 1, 15 grade 2 and 14 grade 3), 19 non-endometrioid (NE) carcinomas (11 serous, 2 clear cell, 6 carcinosarcoma), 3 atypical complex hyperplasias (ACH), 7 hyperplasias without atypia and 19 normal endometriums. FISH probes evaluated included 18q21 (DCC), CEP18, 8q24(MYC), 1q25(LAMC2), 20q13(ZNF217), 2p24(MYCN), 10q26(FGFR2), 2p26(PIK3CA), 10q23(PTEN), CEP 10 and 8p11(FGFR1) (Abbott Molecular Inc). Signal copies for each probe were enumerated in 50 cells from the tissue area of interest.
Results: By CGH, the most common regions of gain in all ECs were 1q21-q41, 1q telomere, 8q24, 8q telomere and 3q27-q29. The most frequent regions of loss were 19p telomere, 9q33.2-q34, 18q 21, 17p12 and 16q22-q24. Differences were observed in the overall frequency and specific regions of gains and losses between EM and NE tumors. A four probe combination of 1q25, 8q24, 8p11 and 20q13 provided the most optimal sensitivity and specificity for the detection of EC in paraffin-embedded tissue sections. Cutoffs for abnormality of each probe were: ≥14% of cells with gains of 1q25 or ≥10% of cells with gains of 8q24 or ≥6% of cells with gains of 20q13 or ≥4% of cells with gains of 8p11. These cutoffs detected of 45/52 cases with EC or ACH (sensitivity 87%) and were negative in all 17 specimens with hyperplasia without atypia or benign endometrium (specificity 100%). The probe set detected 2/3 (67%) of ACH, 10/15 (67%) EM grade 1 tumors, 9/10 (90%) grade 2 tumors and all of grade 3 (n = 10) and NE tumors (n = 14).
Conclusions: This study revealed specific regions of gain and loss that are common in EM and NE EC. A four probe FISH set appears to have high sensitivity and specificity for the detection of EC. However, prospective studies are needed to determine the analytical performance characteristics and clinical utility of this FISH assay.
Category: Gynecologic & Obstetrics

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 172, Wednesday Afternoon

 

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