Ovarian cancer


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  • by the ovarian surface epithelium and the peritoneal and
    fallopian tube epithelia
  • and
    transcriptional signatures, their morphological features
    resemble the specialised epithelia of the reproductive
    tract that derive from the Müllerian ducts.
  • PIK3CA is the gene at chromosome 3q26 that specifi cally encodes the p110α subunit of the phosphatidylinositol-3-kinase (PI3K) protein. *Endometriosis and adjacent
    low-grade endometrioid carcinoma share common genetic events such as loss of heterozygosity at the same loci involving the same allele (eg, PTEN). By contrast, high-grade
    and poorly diff erentiated endometrioid carcinomas are similar to high-grade serous carcinomas.
  • for detecting ovarian cancer in a pelvic mass already known to require surgery
  • results in a 20–30% improvement in both progression free
    and overall survival times by comparison with
    intravenous delivery.57,98–101
  • Ovarian cancer

    1. 1. OVARIAN CANCER •Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. •Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet. 2009 Oct 17;374(9698):1371-82. Epub 2009 Sep 28. • Abraham J, MD. OVA1 test for preoperative assessment of ovarian cancer Commun Oncol 2010;7:249–251 •Köbel M, MD, Huntsman D, MD. Molecular Pathology of Ovarian Carcinomas. Surgical Pathology 4 (2011) 275–296 KAVISA GHOSH M.Phil. Biotecchnology
    3. 3. Estimated incidence and mortality in World
    4. 4. Estimated incidence and mortality in India
    5. 5. OVARIAN CANCER : “THE SILENT KILLER” • Ovarian tumors may arise at any age • Commonest between 30 and 60 • Early stages are asymptomatic & painless • They are liable to become malignant • May develop from: Germ cells- dermoid cysts, teratomas & gonadoblastomas Epithelial or granulosa/ theca cells
    6. 6. • Malignant ovarian cancers: Epithelial ovarian carcinoma Germ-cell tumours Sex-cord stromal tumours Rare typesprimary peritoneal carcinomas, dysgerminomas • Metastases to endometrium, breast, colon, stomach & cervix • 90% of ovarian malignancies are epithelial tumours • Precise cause is unknown • 75% of patients diagnosed with advanced (stage III or IV) disease
    7. 7. • Various risk factors for carcinomas: 1) Genetic disorders BRACA1 & BRACA2 (10–15% of patients, familial cancer) Lynch II syndrome complex or Hereditary Non-Polyposis Colorectal Cancer Breast/ovarian cancer syndrome Autosomal dominant transmission 2) Reproductive 3) Lifestyle • BRACA1 gene mutation epithelial ovarian cancer 39–46% • BRACA2 gene mutation epithelial ovarian cancer 12–20% • History of breast cancer rick of epithelial ovarian cancer (sporadic/nonhereditary ovarian cancers)
    8. 8. Non-Epithelial Tumours - Genetic Disorders 1) Peutz-Jegher syndrome Sex cord, granulosa cell tumours (hormone secreting) 2) Gorlin’s syndrome Ovarian fibroma 3) Gonadal dysgenesis 4) Ollier Disease 5) Maffucci’s syndrome Ovarian granulosa cell tumours with precocious pseudopuberty
    9. 9. Epithelial ovarian cancers • Classified by histopathological grade (1–3) and appearance • Types include: 1) Serous (most common), 2) Mucinous, 3) Endometrioid, 4) Clear cell, transitional, squamous, mixed(Less common) and 5) Undifferentiated subtypes. • Fallopian tube and primary peritoneal cancers morphologically & clinically resemble epithelial ovarian cancers same embryonic precursor
    10. 10. Epithelial ovarian carcinogenesis
    11. 11. Causes and pathogenesis • Subtypes possess unique molecular aberrations & transcriptional signatures • Morphological features resemble epithelia of Müllerian ducts • Derived from surface epithelium precursor cell • Have Specific path of differentiation • Regulated by embryonic pathways involving HOX genes • HOX genes are not expressed in ovarian surface epithelium • HOXA9, HOXA10, and HOXA11 are expressed in abnormal conditions • HOXA7 controls extent of differentiation and grade of ovarian tumours • Sex steroids regulate HOX expression
    12. 12. Origins and molecular pathology of epithelial ovarian cancer subtypes
    13. 13. HOX expression in epithelial ovarian cancers
    14. 14. HOX control of Müllerian differentiation
    15. 15. • High-prevalence somatic (non-germline) mutations >5% • Genes include: TP53,TNNB1, and PTEN (all inactivated) KRAS, PIK3CA,and AKT1 (all activated) Hereditary (germline) BRCA1and BRCA2  occur at an earlier age than sporadic tumours  high-grade serous tumours with P53 dysfunction • Chromosomal instability (gene copy number amplifications and deletions)
    16. 16. Copy number gain in ovarian tumours RAB25 at 1q22  EVI1 (ecotropic viral integration site-1) PRKCi (protein kinase C iota) SKIL  BCL6  the initiation factor EIF5A2  PIK3CA at 3q26·2  MYC and PVT1 at 8q24·2 RSF1 (remodelling and spacing factor 1)  PAK1 at 11q13  HER2 (also known as ERBB2) at 17q12 AKT2 at 19q13·2  ZNF217 AURKA(Aurora Kinase) PTK6 EEF1A2 at 20q13·2
    17. 17. Screening • Early detection might substantially improve survival • CA125 concentration does not have the sensitivity or specificity • CA125 measurement and transvaginal ultrasonography (TVS) • Germline BRCA1 or BRCA2 mutation screening • OVA1 is an FDA-approved test for the evaluation of an ovarian mass prior to surgery. • combines the results of five immunoassays CA-125 II Transthyretin (prealbumin) Apo lipoprotein A1 β2-microglobulin Transferrin • OVA1 indicates a woman’s likelihood of malignancy
    18. 18. Ovarian cancer staging by International Federation of Gynecology and Obstetrics criteria (2002)
    19. 19. Systemic Therapy
    20. 20. Intraperitoneal Chemotherapy • Cisplatin debulked epithelial ovarian cancer • Randomized trials criticized • Not accepted for three reasons: 1)Toxic effects 2)Intraperitoneal treatment delivery issues (eg, technical experience with catheter placement and management) 3)Complications (eg, intraperitoneal adhesions, infections)
    21. 21. Novel Therapeutics & Targets
    22. 22. Ovarian Cancer Monitoring • Non-cancerous conditions, such as ovarian cysts CA 125 level • FDA cleared the HE4 test in 2008 • Alone or with the Cancer Antigen 125 (CA 125)
    23. 23. THANK YOU