Question

Molecular markers in lung carcinoma.

Hint:

Molecular testing is crucial for selecting appropriate therapies in lung cancer, especially EGFR, ALK, and PD-L1 testing, which guide the use of targeted therapies and immunotherapy.

Answer 1

Molecular markers are important in diagnosing and managing lung carcinoma. They provide critical insights into the tumor's behavior and help tailor treatment strategies. The key molecular markers in lung carcinoma include:
Step 1: Genetic Mutations:
1. EGFR Mutations: Epidermal Growth Factor Receptor (EGFR) mutations are commonly found in non-small cell lung cancer (NSCLC), especially in adenocarcinomas. These mutations are targeted by EGFR inhibitors such as erlotinib or gefitinib.
2. ALK Rearrangements: Anaplastic Lymphoma Kinase (ALK) gene rearrangements are found in some NSCLC cases, particularly in younger, non-smokers. Crizotinib and other ALK inhibitors are used for treatment.
3. KRAS Mutations: KRAS mutations are associated with poor prognosis in NSCLC. While no direct therapies are available for KRAS mutations, they guide the understanding of cancer behavior.
4. BRAF V600E Mutation: This mutation is found in a small percentage of lung cancers, and specific BRAF inhibitors like dabrafenib can be used to target this mutation.
5. ROS1 Rearrangements: ROS1 gene fusion is seen in some patients with lung cancer, and targeted therapy with crizotinib can be effective.
Step 2: Protein Expression:
1. PD-L1 Expression: High levels of Programmed Death-Ligand 1 (PD-L1) expression on tumor cells are used to predict the benefit of immune checkpoint inhibitors like pembrolizumab and nivolumab.
2. CEA (Carcinoembryonic Antigen): Elevated CEA levels are seen in many patients with lung cancer, though it is not specific. It can be useful for monitoring response to treatment and detecting recurrence.
Step 3: Other Biomarkers:
1. VEGF (Vascular Endothelial Growth Factor): VEGF is involved in angiogenesis and may be elevated in NSCLC. Targeting VEGF pathways can help in controlling tumor growth.
2. TP53 Mutations: TP53 mutations are commonly found in various cancers, including lung carcinoma, and are associated with poor prognosis.