Targeted Therapy Management in NSCLC Patients Using Cytology: Experience from a Tertiary Care Cancer Center.

BACKGROUND: Although biopsy is the gold standard for diagnosis, cytological material has often been used to assist in making a pathologic diagnosis as well as for molecular testing in certain cancers such as in the lung, cervix, and head/neck. OBJECTIVE: Our objective is to share experience from our institution in the use of cytological material in screening for epidermal growth factor receptor (EGFR) mutations in a subset of patients with non-small cell lung cancer (NSCLC). METHODS: Fine needle aspirates, pleural effusion, cell blocks of 223 NSCLC patients, where cytology suggested malignancy were screened for EGFR mutation in exons 18-21 using Scorpion(®) ARMS real-time polymerase chain reaction (PCR) technology. RESULTS: Overall, EGFR mutation was seen in 43.5 % of study samples. Deletions were highest in exon 19 (27.2 %), followed by exon 21 (15.5 %), exon 18 (5.3 %), and exon 20 (1.9 %). Chi-squared analysis revealed a significant correlation for mutation status in women compared with men (χ (2) = 5.88, p = 0.02), with exon 19 mutation predominating (χ (2) = 5.66, p = 0.02). CONCLUSION: Our results demonstrate the successful use of cytology material for molecular testing in a subset of NSCLC patients to direct their treatment.

Screening for EGFR mutations in lung cancer, a report from India.

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including the lung malignancy. Genetic modifications such as deletions, insertions and Single Nucleotide Polymorphisms in the tyrosine kinase (TK) domain of EGFR is a common feature observed in most lung cancers. Gefitinib and erlotinib are commonly available therapeutic drugs which act as specific inhibitors for the tyrosine kinase domain of EGFR and associated with EGFR mutations in exons 18-21. However the prevalence of mutation varies among ethnicity, grade, age and gender. This is the first report on the prevalence of EGFR mutation in non-small cell lung cancer patients using DNA obtained from samples such as biopsy/cytology/pleural fluid and Fine Needle Aspiration (FNA), across India. We have screened for 29 somatic mutations which span exons 18, 19, 20 and 21 of EGFR gene using Scorpion probe based ARMS-PCR technique. DNA from 220 NSCLC tissue samples were analyzed for EGFR mutations and mutations were detected in 51.8% of the study population. Among the mutant positive cases, the deletions in exon 19 (52%) and a missense mutation L858R in exon 21 (26%) were most predominant. There was a significant increase in overall mutations (p=0.01) as a function of age, mutation in exons 19 and 21 together (p=0.003), mutations in exons 18, 19 and 21 (p=0.04) and mutations in exons 18 and 19 (p=0.03) in females. Mutations did not seem to significantly correlate metastases or disease progression. Mutations in exons [19] and 21 together were significant in non-smokers compared to smokers (p=0.01) using Mann-Whitney tests. The study suggests high prevalence of EGFR positivity in NSCLC in Indian sub-population and provides opportunities for targeted therapies for this group.