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Interactive Session Ovarian Cancer II

Interactive Session Ovarian Cancer II Serous Borderline Tumors of the Ovary: Pathology, Biology, and Management. Jaime Prat, M.D. Nathalie Sieben, M.D. David Gershenson, M.D. Santa Monica, CA October 16, 2006. Surface epithelial ovarian tumors.

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Interactive Session Ovarian Cancer II

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  1. Interactive Session Ovarian Cancer II Serous Borderline Tumors of the Ovary: Pathology, Biology, and Management Jaime Prat, M.D. Nathalie Sieben, M.D. David Gershenson, M.D. Santa Monica, CA October 16, 2006

  2. Surface epithelial ovarian tumors

  3. Ovarian Epithelial Tumors___________________________________________________________________________________________ Serous Mucinous Endometrioid Clear cell Transitional cell Undifferentiated Benign 60% Ca 30% BL 10%

  4. Serous Tumors of the Ovary • Benign 70% • Borderline 5-10% • Carcinomas 20-25%

  5. Borderline Ovarian Tumors (Low Malignant Potential) • Epithelial hyperplasia • Nuclear atypia • Mitotic activity • NO “destructive” stromal invasion WHO 1973-2003

  6. Serous Borderline Tumors Frequency 25-30% of Non-Bg Age 30-50 yrs Bilaterality 30% Stage I 70%

  7. SBT

  8. SBT

  9. Serous carcinoma

  10. Serous Carcinoma Serous Borderline Tumor

  11. Serous Borderline Tumor Diagnostic Features 1. Branching papillae 2. Variable nuclear atypia 3. No stromal invasion

  12. SBT - Micropapillary pattern

  13. SBT - Micropapillary pattern

  14. Mean age 45 37 Bilateral 22/96 (23) 12 (67) Exophytic growth 27/92 (29) 7/16 (44) Stage I 78 (76) 5 (28) II+ 24 (24) 13 (72) (p = 0.0001) Noninvasive implants 20 (83) 12 (92) Invasive implants 4 (17) 1 (8) (a) Microinvasive + micropapillary (3 cases) Prat J, de Nictolis M Am J Surg Pathol 2002 Serous Borderline Tumors Typical Micropapillary n=102 (%) n=18 a(%)

  15. SBT - Micropapillary (More invasive implants?) 1999 Eichhorn et al Possible 2002 Slomovitz et al No 2002 Deavers et al Yes (17% vs 6%) 2002 Prat & De Nictolis No 2003 Gilks et al No 2005 Longacre et al Yes Overall survival similar to typical SBT

  16. Carcinoma (> 3 mm) in SBT-MP

  17. SBT with Microinvasion< 10 mm2 Cumulative literature: Excellent prognosis Stanford data: Risk factor for disease progression

  18. Serous Borderline Tumors (Risk of progression) • Stage • Florid epithelial proliferation • (MP-cribriform pattern) • Microinvasion (?) • Type of peritoneal implants • Other factors yet unidentified • TA Longacre et al • Am J Surg Pathol 2005

  19. Serous Borderline Tumors Peritoneal Implants (30%)

  20. Peritoneal Implants (SBT) • Non-invasive • - Epithelial • - Desmoplastic • Invasive • Bell DA, et al • Cancer 1988; 62:2212

  21. Noninvasive epithelial implant

  22. Noninvasive (desmoplastic) implant

  23. Invasive implant

  24. Invasive implant

  25. Invasive implant

  26. Serous Borderline Tumors (Death from tumor 1984-2005) Non-invasive implantsInvasive implants McCaughey et al2/13 4/5 Bell DA et al3/50 5/6 De Nictolis et al0/10 4/9 Kennedy and Hart1/25 0/1 Seidman and Kurman 1/51 2/3 Gershenson et al 6/73 6/39 Eichhorn et al 0/30 2/3 Bell KA et al 2/29 6/31 Prat and de Nictolis 0/34 3/6 Longacre et al 2/75 5/14 20/390 (5%) 37/117 (32%)

  27. Serous Borderline Tumors Two hypotheses

  28. Serous Borderline Tumors (Genome-wide allelotyping and B-RAF/K-RAS) • 26 specimens from 10 patients • 23 microsatellite markers • Peritoneal implants (6 invasive, 4 noninvasive); lymph nodes (3) • Concordance in 22 tumors of 8 informative patients • Sieben NLG et al • J Pathol (in press) 2006

  29. Sieben N et al. J Pathol (in press) 2006

  30. Serous Tumors (10 yr Survival) BordStageCa 95% 1 54% 91% 1-4 23% 71% 2-4 20%

  31. SBT in Lymph Nodes: 30% LN: Mullerian cysts (endosalpingiosis) SBT in lymph node

  32. Serous Borderline Tumor  Carcinoma

  33. SBT 6th recurrence TCC

  34. Epithelial Ovarian Cancer (Pathogenesis) • Serous Borderline - B-RAF, K-RAS • Serous Ca - p53, LOH 17q21 (BRCA1), • 13q12-q14 (BRCA2, RB1) • Mucinous tumors - K-RAS • Endometrioid Ca - Beta-catenin, PTEN, PIK3CA, • Microsatellite instability

  35. Expression Profiling of Serous Low Malignant Potential, Low-Grade, and High-Grade Tumors of the Ovary. Bonome T, et al. Cancer Res 2005; 65:10602 • Overexpressed in SBT and Low-Grade Carcinoma • p53 • p21 • Cyclin D1 • CIRP • c-FOS • Overexpressed in High-Grade Carcinoma • Cyclin E • CD20 • STAT-1 • Apoliprotein E • Rsf-1

  36. Sieben N et al, J Clin Oncol 2005

  37. Sieben N et al J Clin Oncol 2005

  38. Ovarian Serous Tumors SBT High Grade L G

  39. SBT + MPSCa

  40. SBT + MPSCa MPSCa

  41. Serous Tumors (Pathogenesis - Dualistic model) Bg SBT SBT-MP MP Ca (Inv) G1-2 KRAS and BRAF mutations (70%) Serous Ca G3 p53 mutations, LOH 17q (80%) HER-2/neu amplification/overexpression Singer et al Am J Pathol 2002

  42. SBTs and Serous Carcinomas • SBT-MP pattern is a risk factor within the SBT category rather than a separate category. Poor prognosis only with invasive implants. • Non-invasive implants, common and benign • Invasive implants, rare (12%) and fatal (clonal) • Serous dualistic model (working guide) • Low grade serous carcinomas are rare (B-Raf, K-ras) • High grade serous carcinomas are common (p53, LOH, chromosomal instability)

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