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Ovarian Clear Cell Carcinomas - from the eyes of biological markers

Ovarian Clear Cell Carcinomas - from the eyes of biological markers. Speaker: Cheng MH Modulator: Twu NF Date: Jan 15, 2007. Ovarian Cancer. The U.S. (2001) The 5th most common women’s cancer 13,000 deaths (5%) Taiwan (2002)

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Ovarian Clear Cell Carcinomas - from the eyes of biological markers

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  1. Ovarian Clear Cell Carcinomas- from the eyes of biological markers Speaker: Cheng MH Modulator: Twu NF Date: Jan 15, 2007

  2. Ovarian Cancer • The U.S. (2001) • The 5th most common women’s cancer • 13,000 deaths (5%) • Taiwan (2002) • The 10th most common women’s cancer (729 women, 9.92% of gynecological cancers) • 308 women deaths (0.90%) • The 10th most common women’s death cause

  3. Ovarian Clear Cell Carcinoma • Incidence in ovarian cancers • The U.S.: 5-10% • Taiwan: 9.74% • VGH-TPE: • 9.6% (103/1071) (including missing data) • 2.8% (24/828)

  4. Ovarian Clear Cell Carcinoma • Characteristics of OCCC • Early initial stage, lower surgical substage (Ic, IIc) • Less ascites, smaller tumor volume • Lower pre-operative CA125 • Poorer response to platinum-based chemotherapy • Poorer survival duration and survival rates • Arising from endometriosis? (Cancer 2000;88:2584-9) (J Surg Oncol. 2006;93(5):379-86)

  5. Case Presentation • A case of ovarian clear cell carcinoma • Mrs. C, 46-year-old lady, gravida 3, para 2 • Bilateral cystectomy for endometriomas 10 years ago • Initial presentation of abdominal pain for 2 weeks • Initial stage IV due to supraclavicular lymphadenopathy • Suboptimal surgery followed by serial chemotherapy (taxol, carboplatin, cisplatin, lipodox, topotecan, gemcitabine, Irresa) • Disease progression complicated with embolism

  6. Analysis of Biological Markers tau(+) c-myc(+) Topo2a>10% Topo1(borderline) ERCC1(-) Faint TS P53(-) Her-2/neu(+)

  7. Ovarian Clear Cell Carcinoma • Searching from PubMed • P53: 43 • PTEN: 11 • Her-2/neu: 7 • ERCC1: 1 • Tau: 0 • Topo1: 0 • Topo2A: 0 • TS:0

  8. ERCC1 • Nucleotide excision repair (NER) • Repair of damage to DNA • Rate-limiting step: excision of damage from DNA strand • 16 proteins for repairosome • ERCC1, XPB, …. • Chemoresistance to platinum (Cytotechnology 1998;27:187-201) (Cancer Treat Rev. 1998;24:331-344)

  9. ERCC1 • ERCC1 • Heterodimers with XPB • Incision into 5’ of the site of damage • Positive relationship between ERCC1 mRNA and active DNA repair process • ERCC1 mRNA levels correlates with resistance to platinum-based exposures in ovarian cancers (Biochem. Pharmacol. 2000;60:1305-1313) (Anticancer Res. 2000;20:645-652)

  10. ERCC1 and OCCC • 126 advanced (stage III & stage IV) ovarian ca • RT-PCR (Clinical Cancer Research 2003;9:5299-5305) * * * * * *

  11. PTEN • PTEN/MMAC1/TEP1 • Chromosome 10q23.3 • Tumor suppressor gene • A dual-specificity lipid phosphatase (Science 1997;275:1943-7)

  12. PTEN

  13. PTEN and OCCC • 81 ovarian tumors • PCR and LOH analysis (Cancer Research. 1998;58:2095-2097)

  14. PTEN and OCCC • 40 ovarian clear cell carcinoma • Immunohistochemistry (IHC) (Gynecologic Oncology 2006;101:71-75) * * * * * *

  15. P53 • P53 • Chromosome 17p13.105 • 53-kD • Tumor suppressor gene • Regulate transcription of growth-regulatory gene

  16. P53 and OCCC • P53-positivity • 2.6% (1/38) (Gynecol Oncol 2001;80:189-93)

  17. P53 and OCCC • P53-positivity • 0% (0/13) (Cancer 1999;85:669-77)

  18. P53 and OCCC • P53-positivity • 7.4% (2/27), stage I-II (Int J Oncology 2005;26:177-183) • 0% (0/16), stage II-IV (Int J Gynecol Cancer 2003;13:776-784)

  19. P53 and OCCC • P53-positivity • 64 ovarian ca (37 OCCC, 27 EC) • PCR-SSCP and IHC • No mutations or overexpression • Not a determinant of survival (Gynecologic Oncology 2003;88:318-325)

  20. Her-2/neu • Her-2/neu, c-erb-2 • Chromosome 17q21 • 185-kDa • A component of growth factor receptors • EGFR (Her-1), Her-2, Her-3, Her-4 • For cell differentiation and proliferation • A transmembrane receptor with tyrosine kinase activity • 25-30% overexpression in breast cancers (Semin Oncol 1999;26:51-59)

  21. Her-2/neu

  22. Her-2/neu and OCCC • 15 ovarian clear cell carcinoma • Stage Ia: 20%, Stage Ic: 40%, Stage IIb: 6.7%, Stage IIIb: 6.7%, Stage IIIc: 20%, Stage IV: 6.7% • HercepTest (IHC) (Int J Gynecol Cancer 2003;13,28-31)

  23. Her-2/neu and OCCC (Int J Gynecol Cancer 2003;13,28-31) 6.7%

  24. Her-2/neu and OCCC • 90 ovarian clear cell carcinoma • IHC (Gynecologic Oncology 2004;94:735-739)

  25. Her-2/neu and OCCC • Overexpression of Her-2/neu not related to stage (Gynecologic Oncology 2004;94:735-739)

  26. Her-2/neu and OCCC • Stage I: Her-2/neu(+) not associated with survival P=0.3616

  27. Her-2/neu and OCCC • Stage III: Her-2/neu(+) not associated with survival P=0.9873

  28. Her-2/neu and OCCC • Her-2/neu(+) not associated with lymph nodes metastasis

  29. Her-2/neu and OCCC • 79 early stage (stage I and stage II) • IHC and FISH (Gynecologic Oncology 2004;95:570-575)

  30. Ovarian Clear Cell Carcinoma • “Unclear” from the eye of the biological markers • Rare data • Methodological difference • Variability in IHC • Antigen fixation • Length of storage • Significance of staining system • Interobserver’s difference in the scoring system • Biological markers ≠ Complex regulatory mechanism • ……

  31. Thank You for Your Attension

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