Lecture 27 - Ovarian Cancer Flashcards
What are the four stages of ovarian cancer?
Before ovarian cancer: Healthy ovaries
Stage I: Cancer is confined to one or both of the ovaries
Stage II: Cancer spreads within the pelvic
Stage III: Average stage of diagnosis when cancer spreads to other body parts within the abdomen
Stage IV: Cancer spreads beyond the abdomen
Is ovarian cancer the same disease?
Molecular and genetic analysis has determined that cancer is not a single disease
What are the 5 major histotypes in ovarian cancer (defined by both histology and molecular profiles)?
- High-grade serous carcinoma (>80%)
- Low-grade serous cacinoma
- Endometrioid
- Mucinous
- Clear-cell carcinoma
In the past 20 years, how have the survival rates of ovarian cancer changed?
- There has been no change, meaning survival rates have not improved nor have they decreased
- The 5 year survival rate is between 20-40% depending on the histology of cancer
Why is it important to learn and identify the different histotypes?
- they all have different metabolic traits
- want to accurately diagnose to provide the proper treatment
What are the characteristics of Endometrioid?
- Have tubular glands
- There are solid and cystic regions
- Has an enlarged nuclei and other abnormal features
What are the characteristics of Mucinous?
- It has an expansive pattern of invasion
- There are smooth surfaces
- Multi-lobular (several lobes)
- Has a mucin appearance
What are the characteristics of Low Grade Serous Carcinoma?
- Glandular lined by bland cells
- Has little mitotic activity
- Has normal nuclear morphology (no enlarged nuclei)
What are the characteristics of Clear Cell Ovarian Carcinoma?
- Contains microcystic masses with solid nodules (feels nodule-like)
- Has regions of clear cell-like appearance
What are the characteristics of High-Grade Serous Ovarian Carcinoma?
- Has a papillary/micropapillary (nipple like structure) form
- Contains slit-like spaces between cells
- Is glandular and solid
What are the Type I tumours in ovarian cancer?
- Endometrioid
- Mucinous
- Clear Cell
- Low grade Serous
What are the characteristics of Type I tumours?
- Low grade
- Slow growing
- Encompasses all histologies
- Likely evolve through a step-wise progress from borderline tumours
- Usually chomosomally stable (not picking up mutations frequently)
What are Type II Tumours in ovarian cancers?
- Endometrioid
- Carcinosarcoma
- Clear Cell
- High-grade serous carcinoma
What are the characteristics of Type II Tumours?
- High-grade
- Evolve rapidly
- Includes: high-grade serous carcinoma, high-grade endometrioid carcinoma, carcinosarcoma, undifferentiated carcinoma and some clear cell carcinomas
- No recognizable precursors in the ovary
- Widespread DNA copy number changes
Where are the two locations people have hypothesized ovarian cancer arises from?
- The epithelial cells that line the ovary
- Somewhere on the Fallopian tubes
Explain how a normal or mutant stem cell precursor can become ovarian cancer.
- The mutant stem cell precursor becomes entrapped during ovulation when the surface endothelium was remodeled
- Envagination occurs and results in a cortical inclusion cyst: aberrant niche (which could result in Type II tumours)
- The cyst then becomes a Mullerian metaplasia, if it had not differentiated into a Type II tumour cell, before undergoing malignant transformation
- results in Type I tumours
Explain how ovarian cancer arises from the Fallopian tubes.
- During ovulation, a rupture in the ovary and some of the cells from the fimbriae enter it
- A normal or mutant stem cell precursor undergoes a p53 signature mutation
- The mutations the lead to STIC which undergoes ectropic implantation
- An aberrant niche forms before undergoing a malignant transformation to become a High-grade serous
What stands out when looking at the molecular alterations in the various histotypes of ovarian cancer?
The histotypes all have different molecular feature combinations
eg., High-grade serous carcinoma -> TP53, BRCA1 and P13KCA
What was the first line of treatment 30 years ago?
- Debulking surgery - remove tumour
- Chemotherapy - Platinum
- Radiation - Clear cell ovarian cancer
What was the second line treatment (recurrent disease) 30 years ago?
- Chemotherapy - Platinum
- Repeat
What is the first line of treatment now?
- Neoadjuvant chemotherapy (before surgery)
- Debulking surgery - remove tumour
- Hysterectomy - Removal of uterus
- Unilateral salpingo-oophorectomy - removal of one ovary and Fallopian tube
- Bilateral salpingo-oophorectomy - removal of both ovaries and Fallopian tubes
What is the modern day Second line treatment (recurrent sensitive or resistant)?
Recurrent sensitive
- Chemotherapy - carboplatin, paclitaxel, doxorubicin and gemcitabine
Recurrent resistant
- Chemotherapy - non-platinum single agent, gemcitabine, doxorubicin and paclitaxel
What is the modern day Third Line treatment (recurrent resistant/sensitive)?
- Chemotherapy
- PARP inhibitor (BRCA1 mutation carriers - once approved)
Why are PI3K and Akt signalling important in ovarian cancer?
- PI3K activates AKT downstream
- Akt is the central regulator of signals from the cell surface that leads to proliferation, survival and cell growth
- Akt inhibits the activation of mTOR
- these pathways represent novel targets for the treatment of ovarian cancer and better therapies
