This document provides an overview of ovarian cancer, including its embryology, histopathological classification, staging, presentation, and risk factors. It focuses on BRCA mutations, which account for approximately 40% of ovarian cancer risk. BRCA1 and BRCA2 are tumor suppressor genes, and their mutations impair homologous recombination DNA repair. Around half of high-grade serous ovarian cancers have defects in homologous recombination repair due to BRCA mutations or other genetic lesions. While BRCA testing can identify germline or constitutional mutations, epigenetic silencing also contributes to a "BRCAness" pattern in ovarian tumors lacking BRCA mutations.

1. Gyne-oncology Refresher Series
I- Cancer Ovary
1- Basics foundation I
BY
Ereny s. Saad, MD
Lecturer of clinical oncology, Assiut University, Egypt.
Master of advanced oncology, Ulm University, DE.
European college of oncology fellow.
European Association of Cancer Research Ambassador.
ESMO Accreditation 2019.
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2. Content
1. Embryology and anatomy.
2. Histopathological classification.
3. FIGO staging
4. Presentation.
5. Risk factors and underlying genetic mutations.
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3. 1- Embryology
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4. • The OSE forms a monolayer surrounding the
ovary but is composed of relatively few cuboidal cells
(107 cells per ovary or 0.05% of the entire organ).
• Developmentally, it derives from the celomic epithelium,
which also gives rise to the peritoneal mesothelium and
oviductal epithelium.
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5. 2- Histopathological classification
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8. 3- Staging
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9. Risk factors
• Inherited EOC most often occurs in families with both ovarian and
breast cancer cases or in families with multiple ovarian cancer
cases.
• Inherited ovarian cancer is also part of Lynch syndrome or
hereditary nonpolyposis colorectal cancer
(HNPCC).
• High-penetrance mutations of BRCA1 and BRCA2 account for
approximately 40% of ovarian cancer risk
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10. 1- BRCA (Breast Cancer Gene 1&2)
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11. Tumor suppressor genes:
• It was subsequently recognized that two classes of
tumor suppressors may cooperate:
1. the ones that control proliferation and survival, the so-
called gatekeepers.
2. And the genes involved in the control of genomic
integrity, the caretakers.
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12. Types of DNA damage and
Mechanisms of repair
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13. Homologous vs Non-homologous DNA
repair
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14. Homologous recombination deficiency
HRD Syndrome
molecular analysis of high-grade serous ovarian
cancer (HGSOC) by The Cancer Genome Atlas
(TCGA) has shown that around half have
aberrations in homologous recombination repair
(HRR)
Several genetic lesions causing homologous
recombination deficiency (HRD) include germline
and somatic BRCA mutations as well as mutations
of genes such as ATM, CHEK2, RAD51 and MRE11A
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16. BRCA mutations
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17. Germline (constitutional) versus
somatic
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19. How to get in action
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20. BRCA Testing
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21. The BRCAness
• In the absence of BRCA mutations, the BRCAness
pattern of biological and clinical behavior seems to
be the result of different epigenetic processes.
Indeed, epigenetic mechanisms of transcriptional
silencing are known to inactivate tumor suppressor
genes.
• BRCA1 protein and mRNA levels in ovarian tumors
are decreased or absent in as many as 90% of
patient cases without evidence of germline BRCA1
mutations or family history of BRCA-associated
diseases
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