Related Experiment Video
Updated: Apr 4, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non-Small Cell Lung Cancer: A
S Vatrano1, L Righi1, T Vavalá2
1Division of Pathology, Department of Oncology, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano (Turin), Italy.
Background:
Recently, in advanced non-small cell lung cancer (NSCLC), standard chemotherapy was flanked by biological agents directed against genomic abnormalities, including EGFR and ALK alterations, that significantly improved patient outcome. Despite these achievements, tumour progression almost always occurs and a reassessment of the tumour genetic profile may contribute to modulating the therapeutic regimen. Resampling may provide tissue for additional tests to detect acquired resistance and/or new genetic alterations, but the currently available information is limited.
Patients And Methods:
Histological and genetic reassessments of biopsy or surgical tissue samples from 50 non-squamous NSCLC patients before and after at least one systemic treatment were performed. EGFR, KRAS, BRAF, PIK3CA and HER2 mutations were sequenced, p.T790M was identified with real-time PCR, and ALK and MET genomic alterations by fluorescence in situ hybridization.
Results:
Overall in baseline biopsies, 37/50 (74 %) tumours had genetic alterations, either single (52 %) or multiple (22 %). Among them, 16 were EGFR mutations and 6 ALK rearrangements. In the second tissue sampling, 54 % of cases had additional genomic changes, including newly acquired alterations (81 %) or losses (18 %). The commonest changes were MET amplification and p.T790M mutation. One case had a histological shift from adenocarcinoma to small cell carcinoma.
Conclusions:
The remarkable number of molecular changes following systemic therapy and the genetic complexity of some cases underline the value of histological and molecular re-evaluation of lung cancer to tailor the most appropriate therapy during disease progression.
Insights
Re-evaluating lung cancer tumors after treatment reveals significant genetic changes, including new mutations and amplifications. This molecular reassessment is crucial for tailoring therapy during disease progression in advanced non-small cell lung cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Advanced non-small cell lung cancer (NSCLC) treatment has advanced with targeted therapies for EGFR and ALK alterations.
- Despite improvements, tumor progression remains a challenge, necessitating further investigation into tumor genetics.
- Reassessing tumor profiles after treatment may guide therapeutic adjustments, but data are limited.
Purpose of the Study:
- To investigate the histological and genetic changes in non-small cell lung cancer (NSCLC) after systemic treatment.
- To identify acquired resistance mechanisms and new genetic alterations.
- To evaluate the clinical utility of molecular re-profiling in advanced NSCLC management.
Main Methods:
- Histological and genetic reassessment of biopsy/surgical samples from 50 NSCLC patients pre- and post-treatment.
- Sequencing for EGFR, KRAS, BRAF, PIK3CA, and HER2 mutations.
- Real-time PCR for p.T790M and FISH for ALK/MET genomic alterations.
Main Results:
- 74% of baseline biopsies showed genetic alterations; 16 had EGFR mutations, 6 had ALK rearrangements.
- Post-treatment samples revealed additional genomic changes in 54% of cases.
- Common alterations included MET amplification and p.T790M mutation; one case showed a histological shift to small cell carcinoma.
Conclusions:
- Systemic therapy induces significant molecular changes in NSCLC.
- The genetic complexity observed highlights the importance of re-evaluating lung cancer.
- Histological and molecular reassessment is vital for optimizing therapy during disease progression.
More Related Videos
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
05:00Author Spotlight: Enhancing Multicolor Fluorescence Localization in Lung Carcinoma Sample
Published on: November 21, 2023