Epidermal Growth Factor Receptor Mutation Frequency in Squamous Cell Carcinoma and Its Diagnostic Performance in Cytological Samples: A Molecular and Immunohistochemical Study

Niraj Kumari, Shalini Singh, Dhanjit Haloi, Shravan Kumar Mishra, Narendra Krishnani, Alok Nath, Zafar Neyaz

Abstract


Background: Epidermal growth factor receptor (EGFR) mutation is the most frequent mutation tested in lung cancer for targeted therapy in the era of personalized medicine. Knowledge about EGFR mutation is constantly expanding regarding its frequency, clinicopathological association, advancements in testing methodology and sample requirement. We investigated EGFR mutation frequency in non-small cell lung cancer (NSCLC) in North Indian patients and evaluated its diagnostic performance in cytological samples.

Methods: Molecular EGFR testing was done in 250 cases of NSCLC by both real-time polymerase chain reaction (PCR) (Therascreen) and mutation-specific EGFR immunohistochemistry (IHC). Thirty cases had both cytology samples and biopsy including 20 pleural effusions and 10 fine-needle aspirates. EGFR mutation concordance between pleural effusion and biopsy was studied.

Results: EGFR mutation was overall 31.6% in NSCLC with 36.5% in adenocarcinoma and 15% in squamous cell carcinoma. L858R mutation accounted for 50.7% and DEL19 for 39.3% of total EGFR mutations. Complex mutations were seen in 2% of cases. Sensitivity of mutation-specific EGFR IHC was 48.3% and specificity was 92.3%. L858R showed higher sensitivity (55% vs. 33.3%) but similar specificity (93.2% vs. 91.3%) compared to DEL19. EGFR mutation was successful in 95% of pleural effusion and showed 83.3% concordance with tissue biopsy.

Conclusions: EGFR mutation frequency in North Indian patients was comparable to that of Asia-Pacific region and showed a similar pattern of histological distribution. EGFR mutation in squamous cell carcinomas is increasingly recognized which was 15% in our study. Mutation-specific EGFR IHC shows variable but generally low sensitivity and considering its significant pre- and post-analytical variables, it should be highly discouraged in patient management. Cytological samples may not only serve as suitable alternative but may be complementary to tissue biopsies.




World J Oncol. 2019;10(3):142-150
doi: https://doi.org/10.14740/wjon1204


Keywords


EGFR; Pleural effusion; Mutation-specific IHC; Squamous cell carcinoma; NSCLC

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