1 / 32

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)

knox-browning
Download Presentation

Ovarian Clear Cell Carcinomas - from the eyes of biological markers

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related