Ovarian Clear Cell Carcinomas - from the eyes of biological markers Speaker: Cheng MH Modulator: Twu...
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Transcript of Ovarian Clear Cell Carcinomas - from the eyes of biological markers Speaker: Cheng MH Modulator: Twu...
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) 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
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)
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)
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
Analysis of Biological Markers
Her-2/neu(+)
tau(+) c-myc(+)
Topo1(borderline)Topo2a>10%
ERCC1(-) P53(-)Faint TS
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
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)
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)
ERCC1 and OCCC 126 advanced (stage III & stage IV) ovarian ca RT-PCR
(Clinical Cancer Research 2003;9:5299-5305)
* ** ** *
PTEN
PTEN/MMAC1/TEP1 Chromosome 10q23.3 Tumor suppressor gene A dual-specificity lipid phosphatase
(Science 1997;275:1943-7)
PTEN and OCCC 40 ovarian clear cell carcinoma Immunohistochemistry (IHC)
(Gynecologic Oncology 2006;101:71-75)
* ** ** *
P53
P53 Chromosome 17p13.105 53-kD Tumor suppressor gene Regulate transcription of growth-regulatory gene
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)
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)
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)
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)
Her-2/neu and OCCC Overexpression of Her-2/neu not related to stage
(Gynecologic Oncology 2004;94:735-
739)
Her-2/neu and OCCC 79 early stage (stage I and stage II) IHC and FISH
(Gynecologic Oncology 2004;95:570-575)
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 ……