The Clinical significance of DNA ploidy as a prognostic factor in patients with Borderline Ovarian Tumor Retrospective study Ji Young Lee, MD, PhD, David Marchetti, MD, M Steven Piver, MD Department of Obstetrics and Gynecology Sisters of Charity Hospital, Buffalo, NY INTRODUCTION Howard Taylor Described Borderline Ovarian Tumor as “semi-malignant” ….propensity to metastasize but maintained a rather indolent course… Surg Gynecol Obstet 1929; 48: 204-230 10-20% of epithelial ovarian tumor Mean age 45.7 yr 75% of tumors are Stage I 5 YSR for early stage tumors ≥ 95% Recurrence rate 8~32% Risk factors for recurrence FIGO stage, Age, Residual disease, Histology, DNA ploidy etc. DNA Ploidy The most important prognostic factor in 370 patients with the borderline ovarian tumor Int J Gynecol Oncol 1993 3: 349 A Review of the Literature OBJECTIVES 1. Report the results regarding DNA ploidy and other Clinicopathologic variables 2. Evaluate the clinical significance of DNA Ploidy in 30 consecutive patients with Borderline Ovarian Tumor MATERIALS & METHODS Retrospective Study Review of Cancer Registry of Sisters Hospital A total of 30 consecutive patients with Borderline Ovarian Tumor Histologic evaluation of Paraffin Tissue Blocks DNA Flow Cytometry for DNA ploidy Analysis -Primary Tumor Histology Definition Malignant characteristics of epithelial hyperplasia or stratification, mitotic activity, and cellular/nuclear atypia No Stromal Invasion MUCINOUS TYPE DNA Flow Cytometry by USLABS (Irvine, CA) Diploid ( DI=1.0, single peak) Aneuploid (DI;1.1-1.9), Multi-peak RESULTS ….and DISCUSSION Patients (No.) Age Distribution of Borderline Ovarian Tumor 8 MEAN AGE 54.5 yo 7 6 5 4 3 2 1 0 20-29 30-39 40-49 50-59 60-69 70-79 80-89 Age Age distribution of Borderline Ovarian Tumor Sep 1993 – Sep 2004 in Sweden Int J Gynecol Cancer 2008;18:453–459. Patients (No.) Histology and Age Distribution of Borderline Ovarian Tumor 5 4 Serous 3 Mucinous 2 Mixed 1 0 20-29 30-39 40-49 50-59 60-69 70-79 80-89 Age Patients (No.) DNA Ploidy and Age at Diagnosis 6 Diploid 5 4 Aneuploid 3 2 1 0 20-29 30-39 40-49 50-59 60-69 70-79 80-89 Age The relationship of Histopathology and FIGO stage of disease Serous Mucinous Mixed Total IA 8(50%) 4(50%) 2 14 IB 1(8%) 1 1 3 Stage (%) IC 4(21%) 0 0 4 Total II 0 1 1 2 III 3(21%) 1 0 4 NA 0 1 2 3 16 8 6 30 The relationship of DNA ploidy and Histology of disease DNA ploid Aneuploidy Diploidy Histology Serous Mucinous Mixed 4 (45%) 2 (22%) 3 (33%) 12 (58%) 6 (28%) 3 (14%) Total 9 (100%) 21 (100%) Patients (No.) DNA ploidy and Histologic type 14 12 58% 10 8 28% 6 14% 4 2 0 Serous-Diploid Serous-Aneuploid Mucinous-Diploid MucinousAneuploid Mixed-Diploid Mixed-Aneuploid Histology-DNA Ploidy The relationship of DNA ploidy and FIGO stage of disease DNA ploid Aneuploidy Diploidy FIGO Stage IA IB IC II III Unstaged Total 2 1 2 1 2 1 9 (30%) 12 2 2 1 2 2 21 (70%) pl oi d lo id -D ip -A ne up lo Un id sta ge dDi Un pl sta oi d ge dAn eu pl oi d III III lo id IIAn eu p IIDi IC -A ne up lo id lo id -D ip IC IB -A ne up lo id lo id IB -D ip lo id IA -A ne up IA -D ip lo id Patients (No.) DNA Ploidy and Disease Stage 14 12 Diploid 10 8 Aneuploid 6 4 2 0 Stage-DNA Ploidy Characteristics of 30 patients Characteristics Age < 50 ≥ 50 Ethnicity Caucasian African-American FIGO Stage IA IB IC II-III Unstaged Pelvic Cytology positive Negative Histology Serous Mucinous Mixed Chemotherapy Yes No TOTAL (n=30) Diploid (n=21) Aneuploid (n=9) p value 11 19 5 16 6 3 0.09 29 1 21 8 1 0.002 14 3 4 6 3 12 2 2 3 2 2 1 2 3 1 0.007 6 24 4 17 2 7 0.1 16 8 6 12 6 3 4 2 3 0.4 4 26 3 18 1 8 Histology Borderline Ovarian Tumor Tropé CG. Seminars in surgical oncology 2000 9(1)69 –75 The relation of histopathology to ploidy status Histopathology Serous Mucinous Endometrioid Clear cell Mixed Total Number of cases (%) 219 (54.9) 171 (42.9) 5 (1.2) 1 (0.2) 3 (0.8) 399 Diploid Aneuploid No FCM 167 127 3 — 2 27 32 2 1 1 25 12 — — — 299 63 37 Int J Gynecol Cancer 2008;18:453–459. Overall Recurrence and survival in Borderline ovarian tumor Stage I Stage II & III Total N 686 219 905 Recurred 29 40 69(7.6%) Died 9 22 31(3.4%) Rubin SC, Sutton GP (2001,Ovarian cancer 2nd edition) DNA Ploidy and Prognosis in Borderline Ovarian Tumor (I) Cancer 1992 69(10): 2510 DNA Ploidy and Prognosis in Borderline Ovarian Tumor (II) Seidman JD et al. Cancer 1993;71:12 …DNA ploidy may be of little prognostic importance Harlow BL et al. 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