Molecular Pathology Flashcards
What is molecular pathology?
Study of molecular and genetic basis of diseases, examining alterations in genes, proteins, and other molecular components that contribute to the development and progression of diseases.
What is Histopathology)
Branch/classification of molecular pathology examining what the tissue/tumour looks like.
Histopathology: examination of tissues and cells under a microscope for analysis of morphological features to identify abnormalities, such as changes in cell structure, tissue architecture, and the presence of specific cellular patterns.
Based on cell patterns:
- Carcinoma (epithelium), Adenocarcinoma (glandular epithelium), Squamous cell carcinoma (from squamous epithelium), Sarcoma (from connective tissues)
What is functional molecular pathology based on?
How disease affects cellular functions and contribute to the overall pathology of a disease. This is based on what the cell does: Receptors expressed, genes present, mutations…
What does morphology in molecular pathology tell us
Cell type / tissue of origin
Differentiation
Stage
Grade
Limitations of morphology in molecular pathology
- Limited Information on Molecular Alteration.
- Heterogeneity of Diseases: different patients or even different regions within the same tumor may exhibit distinct molecular profiles.
- Inability to Identify Subtle Molecular Changes
- Limited Predictive Power for Treatment Response
- Incomplete Understanding of Disease Mechanisms
- Challenges in Distinguishing Between Benign and Malignant Lesions
Limitations of functional molecular pathology
- Complexity of Biological Systems
- Incomplete Knowledge of Molecular Interactions
- Variability Among Individuals
- Technical Challenges in Functional Assays:
- Dynamic Nature of Cellular Processes
- Integration of Data from Multiple Omics Technologies
- Limited Accessibility to Advanced Technologies
- Ethical and Privacy Concerns
Pathology vs molecular pathology
-Pathology is evolving and molecular pathology is a significant aspect of this.
- Traditional pathology : examination of tissues and cells under a microscope to diagnose diseases and understand their morphological characteristics.
- Molecular pathology: focuses on molecular and genetic aspects of disease analysing DNA RNA, Proteins and other molecular markers to understand underlying mechanisms of disease/ identify specific genetic mutations/ guide personalised treatment strategies.
- traditional and molecular pathology techniques are often combined to offer a more thorough understanding of diseases.
Why is there no change in understanding/prognosis of lung cancer?
- Seen as self inflicted (smoking stigma)
- Lack of funds means lack of research
Molecular Pathology -IHC for lung cancer diagnosis
Commonly used in differentiation and classification of lung cancer types
Involves antibodies to detect specific proteins in tissue samples
- IHC often employed to identify and characterise certain proteins associated with different types of lung cancers
- Common types of lung cancers are NSCLC and SCLC. Further subtypes of cancer within NSCLC (e.g adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. ).
-IHC helps pathologists distinguish between these subtypes based on expression of specific markers
- Useful for personalised medicine.
Molecular Pathology -IHC for lung cancer diagnosis (Markers)
- TTF-1 (Thyroid Transcription Factor -1) - often expressed in lung adenocarcinomas as a positive stain
- p40 and p63: often used to distinguish between adenocarcinoma and squamous cell carcinoma which typically shows strong positive straining for p40 and p63
- Ck7 and ck20: markers used to differentiate between lung adenocarcinoma and colorectal carcinoma. Adenocarcinomas from these two sires have distinct staining patterns
Treatments for lung cancer
Chemotherapy
Radiotherapy
Chemo-radiotherapy
Surgery
Immunotherapy (new)
Limitations of chemotherapy
Limited specificity
Best guess
Trial and error
Immunotherapy
- Relies on knowing what to target
- Newer tech (NGS, qPCR) allows us to know what is happening in the tumour so we know what will work for the patient instead of just what usually works best.
- approach often involves identifying specific proteins that are produced by the mutated genes and using immunotherapy to enhance the immune system’s ability to recognize and destroy cells expressing those proteins.
What is PD1?
What is PDL1?
Functions
PD1: Programmed Cell Death Protein 1. Down regulates T cells as part of managing the immune system to prevent inappropriate immune responses/ potential peripheral tissue damage
PDL1: Ligand expressed on some tumour cells against PD1 to downtrgulate the immune response against the tumour, worsening prognosis.
PDL1 and NGS
NGS used to detect tumours for PDL1.
These tumours can be treated with PD-L1 inhibitors. (monoclonal antibodies)
