[Histologic subtyping of poorly-differentiated solid lung cancer with molecular testing for epidermal growth factor...

Objective: To study the histological subtyping of poorly differentiated solid lung cancer by using immunohistochemistry and mucin staining along with analysis of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement. Methods: Among 827 cases of non-small cell lung cancer at Beijing Hospital from April 2014 to April 2017, 167 cases of solid poorly differentiated lung cancer were identified and histopathologically subtyped by mucin staining (D-PAS) and immunohistochemistry using 10 antibodies (CK7, vimentin, Ki-67, CK5/6, p40, TTF1, Napsin A, CD56, chromogranin A, and synaptophysin). Paraffin embedded tumor samples were subjected to mutation analysis of exons 18, 19, 20 and 21 of the EGFR gene by amplification refractory mutation system (ARMS) method. Immunohistochemistry (Ventana D5F3) for ALK gene rearrangement was performed followed by ALK fluorescence in situ hybridization (FISH) verification. Results: There were 79 females and 88 males in the study cohort. The patient's age ranged from 35 to 77 years (mean 62 years). Cases with solid growth pattern (at least >10%) and without typical histological features of adenocarcinoma, squamous cell carcinoma or neuroendocrine carcinoma were further divided based on immunohistochemistry and mucin stain into 64 cases(38.32%)of adenocarcinoma, 34 cases(20.35%) squamous cell carcinoma, 21 cases(12.57%)large cell neuroendocrine carcinoma, 5 cases(2.99%)combined large cell neuroendocrine carcinoma, 2 cases(1.20%)adenosquamous carcinoma and 41 cases(24.55%)large cell carcinoma. The Ki-67 positive rate ranged from 5% to 65%. Mutations of EGFR were detected in 5 cases (2.99%, 5/167) of adenocarcinoma(19del in 3 cases and L858R in 2 cases). Two cases(1.20%, 2/167) with ALK-rearranged were identified by immunohistochemistry (Ventana D5F3) and confirmed by ALK FISH. Conclusions: Poorly differentiated solid lung cancer without distinct morphological features can be further histologically subtyped by mucin staining and immunohistochemistry. Molecular testing should be performed for accurate molecular target therapy to improve the prognosis.