title: Immunohistochemical differential diagnosis between large cell neuroendocrine carcinoma and small cell carcinoma by tissue microarray analysis with a large antibody panel.
abstract: 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 beta-catenin, 191 vs 120 (P < .0286). Immunostaining of cross-sections containing LCNEC and SCLC components revealed significant expression of CK7, CK18 and beta-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 beta-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.
authors.affiliation: Pathology Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa-shi, Chiba 277-8577, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nitadori
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Murata
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kodama
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.forename: Harubumi
authors.initials: H
authors.lastname: Kato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D018287:Carcinoma, Large Cell / Q000737:chemistry / Q000175:diagnosis* / Q000601:surgery; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry / Q000175:diagnosis* / Q000601:surgery; D018288:Carcinoma, Small Cell / Q000737:chemistry / Q000175:diagnosis* / Q000601:surgery; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D053552:Keratin-7; D007633:Keratins / Q000032:analysis; D008175:Lung Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000601:surgery; D009363:Neoplasm Proteins / Q000032:analysis; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; C507497:KRT7 protein, human; D053552:Keratin-7; D009363:Neoplasm Proteins; D051176:beta Catenin; D007633:Keratins