7. Molecular pathological diagnosis of tumors Flashcards
What are the uses of molecular pathology?
- additional study to confirm/make the diagnosis
- define genetic abnormalities associated with prognosis
- predictive for effectivenesx of therapy
What are the methods of molecular pathological diagnostics?
- immunohistochemistry
- in situ hybridisation techniques
- PCR-based methods
What does immunohistochemistry detect?
proteins
What do situ hybridisation techniques detect?
longer DNA sequences, translocation, amplifications
What do PCR-based methods detect?
smaller abnormalities and mutations of the DNA
What is next generation sequencing?
- sufficiently sensitive method
- simultaneously test several genes from the samples of multiple patients
Molecular pathology of colon adenocarcinomas
- RAS (KRAS, NRAS) mutation: if positive, resistant to anti-EGFR therapy
- BRAF mutation: if negative, can indicate sporadic MSI
- MSI (microsatellite instability): tests DNA repair enzyme proteins and MS markers, if MSI is positive then the tumor reacts favorable to immunotherapy
Molecular pathology of non small cell lung carcinoma
- most common for lung adeno carcinoma is an activation mutation in exon 2 of KRAS gene (30%), usually as a result of smoking
- KRAS mutant lung cancers are resistant to EGFR-inhibitor therapy and is one of the prognostically least favorable cancers
- PD-L1 protein expression and MSI: predictive markers for immune checkpoint inhibition therapy (effective against AC and SCC)
Molecular pathology of breast carcinoma
IHC testing for:
- Ki-67 proliferation index: primarily prognostic
- ER and PR expression: predictive of reaction to hormone therapy
- HER2 protein expression indicates sensitivity to HER2 inhibitor targeted therapy
BRCA 1-2 mutation: predictive biomarker for platinum-based treatments, and indicates sensitivity to PARP inhibitors
When is BRCA 1-2 gene mutation present?
- tripple negative breast cancers (ER, PR, HER2 negative)
- hereditary breast cancer
- sporadic breast cancer
