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Understanding Biomarkers of Ovarian Cancer and Cysts: A Comprehensive Lecture by Dr. Usman Ghani

This lecture covers the risk factors, causes, diagnosis, and treatment of Polycystic Ovarian Syndrome (PCOS) and ovarian cancer, focusing on the role of insulin resistance, androgens, and the CA-125 biomarker in diagnosis. It details the formation of ovarian cysts, endocrine changes, and diagnostic criteria for PCOS, along with discussing types, risk factors, and diagnostic methods for ovarian cancer. The importance of biomarkers and early detection through CA-125 testing is emphasized.

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Understanding Biomarkers of Ovarian Cancer and Cysts: A Comprehensive Lecture by Dr. Usman Ghani

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  1. Biomarkers ofovarian cancer and cysts Reproduction System Block Dr. Usman Ghani

  2. Objectives By the end of this lecture, the Second Year students will be able to: • Discuss the risk factors and possible causes of polycystic ovarian syndrome (PCOS) and ovarian cancer • Comprehend the role of insulin resistance and hypersecretion of androgens in the development of PCOS • Identify avenues for the diagnosis and treatment of PCOS and ovarian cancer • Assess the diagnostic significance of CA-125 in ovarian cancer

  3. Overview • Polycystic ovarian syndrome (PCOS) • Causes • Endocrine changes • Diagnostic criteria • Treatment • Ovarian cancer • Types, risk factors • Diagnosis • CA-125 biomarker

  4. Polycystic ovarian syndrome • Formation of multiple small cysts in the ovaries • Affects 5-10% of women (20% in some populations) • A major cause of infertility in women

  5. Polycystic Ovarian Syndrome

  6. Polycystic ovarian syndrome Strongly correlated to: • Hypersecretion of leutinizing hormone (LH) and androgens (testosterone) • Low levels of SHBG (sex hormone-binding globulin) Family history Obesity (40%) Hirsutism Chronic anovulation Glucose intolerance Insulin resistance Hyperlipidemia Hypertension Menstrual disorders

  7. Polycystic ovarian syndrome • Exact cause of the syndrome is unknown • May be multifactorial (genetic and environmental) Probable causes: • Insulin resistance causes excessive androgen production in ovaries (common) • Abnormalities in ovaries, adrenal and pituitary glands

  8. Endocrine changes in PCOS LH ↑ FSH ↓ ↑ plasma [oestrone] Stimulation of ovarian stroma & theca by LH Anovulation Hirsutism Aromatisation in adipose tissue ↑ Androgens & free androgens ↓SHBG Obesity Insulin resistance

  9. Diagnostic criteria for PCOS • European Society for Human Reproduction & Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM) recommendation: • At least two of the following features are required for PCOS diagnosis: • Oligo-ovulation or anovulation manifested as oligomenorrhea or amenorrhea • Hyperandrogenism (clinical and biochemical evidence of androgen excess) • Polycystic ovaries (as defined by ultrasonography) Ref: PCOS Consensus Workshop Group. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. Jan 2004;81(1):19-25

  10. Polycystic ovarian syndrome • Diagnosis done by measuring: • Free testosterone (total testosterone is less sensitive; androgens are increased in PCOS) • Sex hormone-binding globulin (SHBG; decreased in PCOS) • Leutinizing hormone (LH; high in 60% cases) • Follicle stimulating hormone (FSH); usually normal in PCOS

  11. Polycystic ovarian syndrome • Diagnosis done by measuring: • Fasting blood glucose • Insulin • Lipids • Ovarian ultrasound • 30% of patients do not have ovarian cysts despite having symptoms

  12. Treatment of PCOS: Break the cycle LH ↑ FSH ↓ ↑ plasma [oestrone] Stimulation of ovarian stroma & theca by LH Anovulation Hirsutism Aromatisation in adipose tissue ↑ Androgens & free androgens ↓SHBG Obesity Insulin resistance

  13. Treatment of PCOS Aim of treatment: interrupt the cycle of obesity, insulin resistance, excess androgens • Reduce LH levels (by oral contraceptives) • Reduce body weight • Increase FSH levels (by clomiphene, etc.) • Estrogen replacement therapy • In select women after careful risk counseling

  14. Ovarian cancer A leading cause of death because of gynecologic cancer Due to malignant transformation of ovarian epithelial cells Most common type of ovarian cancer

  15. Ovarian cancer Subtypes: • Serous (46%): surface epithelial tumors • Mucinous (36%): mucinous epithelial tumors • Endometrioid (8%): endometrial tumors

  16. Ovarian cancer Risk factors Nulliparity (woman with no child birth or pregnancy) Family history of breast, ovarian, colorectal cancer Mutations in BRCA1 and BRCA2 genes (most common) Carriers of BRCA1 mutations have a cancer risk of 44%

  17. Ovarian cancer Premenopausal breast cancer or ovarian cancer indicates higher risk for hereditary or breast cancer Ashkenazi Jews have higher risk of ovarian cancer

  18. Ovarian cancer Biomarkers and diagnosis Epithelial ovarian cancer is commonly diagnosed at a later stage Due to non-specific symptoms such as abdominal pain, blotting, early satiety, nausea, etc. Most patients (75%) have advanced-stage tumor upon diagnosis

  19. Ovarian cancer • Diagnosis includes: • History taking • Physical examination • Ultrasound • Measurement of serum CA-125 levels

  20. Cancer antigen 125 (CA-125) The only serum marker of epithelial ovarian cancer A cell surface glycoprotein expressed in the epithelium of all tissues Normally absent in serum CA-125 is elevated in ovarian cancer >35 U/ml is considered positive

  21. Cancer antigen 125 (CA-125) • Recommended as an annual test for women with family history of ovarian cancer • CA-125 is associated with stages of ovarian cancer • Elevated in: • 50% of patients with stage I • 90% of patients with stage II • >90% of patients with stage III and IV

  22. Cancer antigen 125 (CA-125) • A non-specific marker • False positive CA-125 conc. are found in benign conditions: • Endometriosis • Uterine leiomyomas • Pelvic inflammatory disease • During the first trimester of pregnancy • During menstruation • Some patients (< 50 years) have elevated CA-125 due to unrelated malignant mass

  23. Cancer antigen 125 (CA-125) • CA-125 is not a marker of choice for ovarian cancer screening due to: • Low prevalence of ovarian cancer • High false-positive rate • Useful in: • Monitoring patient’s response to chemotherapy • Success of surgery (de-bulking procedures) • Annual testing for women with family history of ovarian cancer

  24. Take home message • PCOS is strongly correlated to insulin resistance and endocrine abnormalities. • Although a nonspecific biomarker, CA-125 is important for staging and follow-up of ovarian cancer treatment

  25. References • Sheehan, MT. Polycystic ovarian syndrome: diagnosis and management. Clin. Med. Res., 2003, 2(1): 13-27 • Sundar, S. Diagnosis of ovarian cancer, BMJ, 2015, 351:h4443.

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