title: Large cell neuroendocrine carcinoma of the lung: a comparison with large cell carcinoma with neuroendocrine morphology and small cell carcinoma.
abstract: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a malignant neuroendocrine tumor clinicopathologically similar to and falling in-between atypical carcinoid tumor and small cell lung carcinoma (SCLC). The diagnosis of LCNEC is based mainly on a characteristic neuroendocrine morphology and biological neuroendocrine differentiation. In order to know the discrepancy between morphological and biological neuroendocrine differentiation, LCNEC was immunohistochemically and molecular biologically compared with large cell carcinoma with neuroendocrine morphology (LCCNM), which lacked only biological neuroendocrine differentiation among the criteria of LCNEC. Immunohistochemically, disruption of the RB pathway, namely a lack of RB expression and simultaneous overexpression of p16 protein, was characteristic of LCNEC, but not LCCNM. In G2/M cell cycle regulation, 14-3-3 sigma expression was markedly reduced in LCNEC. Moreover, the antibody 34 beta E12 recognizing a set of large-sized keratin gave a different staining pattern between LCNEC and LCCNM. The immunohistochemical data suggested that LCNEC has a similar biological marker profile to SCLC and different from LCCNM. However, a loss of heterozygosity (LOH) analysis using microsatellite markers showed a high frequency of LOH at 3p in both LCNEC and LCCNM as well as in SCLC. Morphological neuroendocrine differentiation might not be identical to biological neuroendocrine differentiation in large cell carcinoma of the lung.
authors.affiliation: Department of Tumor Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. wxpeng@med.gunma-u.ac.jp
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Peng
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sano
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawashima
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000368:Aged; D000912:Antibodies, Neoplasm / Q000032:analysis; D018278:Carcinoma, Neuroendocrine / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000276:immunology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D012189:Retrospective Studies
chemical_list: D000912:Antibodies, Neoplasm; D016160:Retinoblastoma Protein; D007633:Keratins