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Immunohistochemical Differential Diagnosis Between Large Cell Neuroendocrine Carcinoma and Small Cell Carcinoma by Tissue Microarray Analysis With a Large Antibody Panel

Jun-ichi Nitadori MD, Genichiro Ishii MD, Koji Tsuta MD, Tomoyuki Yokose MD, Yukinori Murata MT, Tetsuro Kodama MD, Kanji Nagai MD, Harubumi Kato MD, Atsushi Ochiai MD
DOI: http://dx.doi.org/10.1309/DT6BJ698LDX2NGGX 682-692 First published online: 1 May 2006


To elucidate additional phenotypic differences between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), we performed tissue microarray (TMA) analysis of surgically resected LCNEC and SCLC specimens. Immunostaining with 48 antibodies was scored based on staining intensity and the percentage of cells that stained positively. Four proteins were identified as significantly expressed in LCNEC as compared with SCLC: cytokeratin (CK)7, 113 vs 49 (P < .0301); CK18, 171 vs 60 (P < .0008); E-cadherin, 77 vs 9 (P < .0073); and β-catenin, 191 vs 120 (P < .0286). Immunostaining of cross-sections containing LCNEC and SCLC components revealed significant expression of CK7, CK18, and β-catenin in the LCNEC component compared with the SCLC component in 2 of 3 cases. Our results indicate that significant expression of CK7, CK18, E-cadherin, and β-catenin is more characteristic of LCNEC than of SCLC, and these findings provide further support that these tumor types are separate entities morphologically and immunophenotypically, if not biologically.

Key Words:
  • Lung cancer
  • Large cell neuroendocrine carcinoma
  • Small cell carcinoma
  • Tissue microarray
  • Immunohistochemistry
  • Large antibody panel