What is brca?
The name BRCA is an abbreviation of Breast Cancer gene.BRCA1 and BRCA2 are in the same DNA repair pathway both are Tumour supressors .When they losing their function promotes cancer .BRCA1 gene mutation on chromosome 17, BRCA2 gene mutation chromosome 13. BRCA1 more carcinogenic than BRCA2 it occur earlier in life with one family member affected. The risk increase with age upto 70yr . pattern of inheritance AD and ovarian tumour occur at younger age below 50yr associated with risk of breast and colonic cancer.
What is their effect?
Men:prostate,testicle
Both: pancreatic ca,malignant melanoma,glioblastoma
ETIOLOGY
Etiology not well known.
Hereditary or familial ovarian cancer:
1.BRCA1&BRCA2 mutation
2.Ras oncogene
3.p53 mutation
Pathology:
-Epithelial ovarian cancer accounts for 80-90% of
ovarian cancer
-non-epithelial cancer account for 10-20%
Types of ovarian cancer:
The ovaries are made up of 3main kinds of
cells.
These includes malignancy:
1.Germ cell origin
2.sex cord stromal cell origin
3.metastatic cancer and
4.Rare malignancy like lipoid cell tumours,sarcomas
Pathogenesis:
Ovarian carcinogenesis can be divided into two broad phases:
- Malignant transformation
- Benign ->borderline ->malignant ovarian tumours.
- Peritoneal dissemination
New model carcinogenesis :
Surface epithelial tumours divides into 2 broad
categories: TYPE1 &TYPE 2
Based on their clinico-pathologic features and characteristic molecular genetic changes.
clinical feature:
- Screening Unfortunately,there are no good screening methods for ovarian cancer at present; Most use a combination of physical exam ,CA125 levels and TVS .
- No role of routine screening in general population
- Some follow women with high risk factors(eg:family hx,BRCA mutation )using CA-125 and TVS DIAGNOSTIC CRITERIA OF OVARIAN CANCER
ultrasonography :
- ovarian vol >10cm, septal thickness >2mm,papillary excrescences, thickeness of cyst wall:3mm
- CEA >5ng/ml ;CA 125(80% raised in epithelial tumour),LDH,HCG,AFP, other routine test CT and MRI
- PET scan for distant disease Confirmed by cytology or tissue dx:
- Paracentesis
- FNAC
surgical specimen FIGO staging:
STAGE 3: Positive retroperitoneal lymph nodes and microscopic metastasis beyond pelvis
IIIA: Microscopic peritoneal metastasis beyond the pelvis
IIIB: Microscopic peritoneal metastasis beyond the pelvis 2cm or less in greatest dimension
IIIC: Microscopic peritoneal metastasis beyond the pelvis more than 2cm in greatest dimension and/or regional lymph nodes metastasis
STAGE 4: Distant metastasis beyond the peritoneal cavity, liver parenchymal metastasis
Management:
Early ovarian cancer (stage 1 and 2) surgical staging and debulking
- Ascites fluid cytology or peritoneal washings
- Total abdominal hysterectomy
- B/L salpingo -oophorectomy
- Pelvic and para-aortic lymphadenectomy
- Multiple peritoneal biopsies
- Stage 3&4 3-6cycles of chemotherapy Carboplatin and paclitaxel-standard combination.
