The Correlation Between Histologic, Immunophenotypic, and Molecular Characteristics of Pulmonary Sarcomatoid Carcinoma Reveals That Sarcomatoid Change Is Potentially Derived From Epithelial Carcinoma Cells Undergoing Epithelial-Mesenchymal Transition.

Abstract

Pulmonary sarcomatoid carcinoma (PSC) is characterized by biphasic tumors with epithelial and mesenchymal phenotype. Little is known about the correlation between histologic, immunophenotypic features and the genetic profile of PSC. We analyzed the expression of epithelial-mesenchymal transition-related markers, adenocarcinoma (ADC) and squamous cell carcinoma lineage-specific markers of 205 PSC cases. The alteration of 5 targeted genes was detected by amplification-refractory mutation system-polymerase chain reaction. The intensity of cytokeratin staining was stronger in epithelial carcinoma (EC) than that of the sarcomatoid component (SC) of pleomorphic carcinoma, while vimentin was positive in only 16.3% (17/104) of EC of pleomorphic carcinoma. There is no significant difference between thyroid transcription factor 1 (TTF-1) expression in the SC (46.5%, 33/71) of pleomorphic carcinoma with ADC components and pure PSC (44.2%, 42/95) without p40 expression ( P =0.858). Four cases with ALK rearrangement were confirmed to co-express ALK fusion protein in both the SC and EC. The incidence of EGFR/ALK/KRAS mutation was similar between pleomorphic carcinoma with ADC components (40.6%, 26/64) and TTF-1 + pure PSC (38.2%, 13/34) ( P =0.583). However, higher proportions of TTF-1 + /p40 - PSC patients (44.8%, 39/87) had EGFR/ALK/KRAS mutation than those with TTF-1 - /p40 - PSC (16.7%, 4/24) ( P =0.031). The incidence of EGFR mutation was significantly higher in TTF-1-positive (18.4%, 16/87) than TTF-1-negative (2.7%, 2/74) PSC ( P =0.002). No EGFR and ALK abnormality were observed in 24 pleomorphic carcinoma cases with squamous cell carcinoma components or pure PSC with p40 expression. Our study reveals a close correlation between SC and EC components of pleomorphic carcinoma in terms of immunophenotypic and genetic features, which suggests that pleomorphic carcinoma is potentially derived from the sarcomatoid change of EC cells undergoing epithelial-mesenchymal transition.