Expression of p63 and TTF1 in Non-small Cell Lung Carcinoma with Special Reference to Mutation of EGFR and ALK in Adenocarcinoma of the Lung: An Institutional Experience

Abstract Background: Lung cancer is one of the most common cancers accounting for 11.4% of all newly detected cancers leading to over 1.7 million deaths every year. As the majority of the tumors are unresectable, the newly developed treatment modalities including the tyrosine kinase inhibitors (TKI) and anaplastic lymphoma kinase (ALK) inhibitors have led to greater emphasis on histologic subtyping and biomarker status of these tumors. Aim and Objectives: To classify non-small cell lung carcinoma (NSCLC) concerning histomorphology, immunohistochemistry (IHC), and further evaluation of epidermal growth factor receptor (EGFR) mutation and ALK rearrangement in adenocarcinoma with respect clinicopathological features as well as therapeutic response. Materials and Methods: A total of 126 cases of biopsy-proven NSCLC were selected. EGFR and ALK mutation analysis was performed in 48 and 44 cases, respectively. Results: Adenocarcinoma was the most common NSCLC (83.3%), which showed a higher positivity rate of TTF1 (94.9%) than Napsin A (85%) and p63 was expressed in 17.2% of cases. EGFR mutations were positive in 43.7% of cases, showing higher incidence in females and Grade II tumors. ALK mutation was positive in 6.8% of cases and was seen predominantly in females with a higher incidence of solid morphology tumors than EGFR mutations. One year follow-up of patients showed all ALK-positive tumors were highly responsive to targeted therapy even in high-grade tumors. Cases positive for EGFR mutations on Exon 19 and Exon 21 showed good response with TKIs. Conclusion: In the era of personalized medicine, the lung cancer classification strives on tumor cell morphology, IHC, and molecular analysis for optimal therapeutic management and prognosis.