Genetic alterations in early-stage pulmonary large cell neuroendocrine carcinoma

被引:38
作者
Hiroshima, K
Iyoda, A
Shibuya, K
Haga, Y
Toyozaki, T
Iizasa, T
Nakayama, T
Fujisawa, T
Ohwada, H
机构
[1] Chiba Univ, Grad Sch Med, Dept Basic Pathol, Chiba 2608670, Japan
[2] Chiba Univ, Grad Sch Med, Dept Thorac Surg, Chiba 2608670, Japan
[3] Chiba Univ, Grad Sch Med, Dept Med Immunol, Chiba 2608670, Japan
关键词
lung; large cell neuroendocrine carcinoma; small cell carcinoma; loss of heterozygosity; methylation; p16; p53; retinoblastoma protein;
D O I
10.1002/cncr.20108
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are high-grade malignant neuroendocrine tumors. Histologic differentiation between SCLC and LCNEC is difficult in some cases and to the authors' knowledge, genetic alterations associated with LCNEC have not been identified. Therefore, the authors studied genetic alterations found in LCNEC and compared them with those of SCLC and classic large cell carcinoma (CLCC). METHODS. Twenty-two patients with UICC TNM Stage I LCNEC, 12 patients with Stage I CLCC, and 11 patients with SCLC with limited disease were studied. All tumors were resected completely. Loss of heterozygosity (LOH) of the tumor cells was detected using fluorescent primers. Methylation status of the p16 gene and expression of the p53 protein, retinoblastoma protein, and p16 protein were evaluated immunohistochemically. RESULTS. LOH at TP53 and 13q14 was observed in most patients. The prevalence of LOH at D3S1295, D3S1234, and D5S407 was significantly higher in patients with LCNEC and SCLC than in patients with CLCC. The prevalence of LOH at D5S422 was higher in patients with CLCC and in patients with SCLC than in patients with LCNEC. Expression of the p16 protein was observed more frequently in SCLC than in CLCC or LCNEC. Hypermethylation of the p16 gene was observed more frequently in LCNEC than in SCLC. Patients with allelic losses at D3S1234 and DIOS1686 had poorer prognoses compared with patients without allelic losses at these sites. CONCLUSIONS. Genetic alterations of LCNEC were akin to those of SCLC. However, allelic losses at 5q and abnormalities in the p16 gene may differentiate LCNEC from SCLC. (C) 2004 American Cancer Society.
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页码:1190 / 1198
页数:9
相关论文
共 36 条
[1]   Aberrant methylation of p16INK4a is an early event in lung cancer and a potential biomarker for early diagnosis [J].
Belinsky, SA ;
Nikula, KJ ;
Palmisano, WA ;
Michels, R ;
Saccomanno, G ;
Gabrielson, E ;
Baylin, SB ;
Herman, JG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (20) :11891-11896
[2]   FREQUENCY OF HOMOZYGOUS DELETION AT P16/CDKN2 IN PRIMARY HUMAN TUMORS [J].
CAIRNS, P ;
POLASCIK, TJ ;
EBY, Y ;
TOKINO, K ;
CALIFANO, J ;
MERLO, A ;
MAO, L ;
HERATH, J ;
JENKINS, R ;
WESTRA, W ;
RUTTER, JL ;
BUCKLER, A ;
GABRIELSON, E ;
TOCKMAN, M ;
CHO, KR ;
HEDRICK, L ;
BOVA, GS ;
ISAACS, W ;
KOCH, W ;
SCHWAB, D ;
SIDRANSKY, D .
NATURE GENETICS, 1995, 11 (02) :210-212
[3]  
Campiglio M, 1999, CANCER RES, V59, P3866
[4]  
Gasparotto D, 1999, INT J CANCER, V84, P432, DOI 10.1002/(SICI)1097-0215(19990820)84:4<432::AID-IJC18>3.0.CO
[5]  
2-#
[6]   Mechanisms of p16INK4A inactivation in non small-cell lung cancers [J].
Gazzeri, S ;
Gouyer, V ;
Vourc'h, C ;
Brambilla, C ;
Brambilla, E .
ONCOGENE, 1998, 16 (04) :497-504
[7]  
Girard L, 2000, CANCER RES, V60, P4894
[8]  
GRAY IC, 1995, CANCER RES, V55, P4800
[9]   Quantitative expansion of structural genomic alterations in the spectrum of neuroendocrine lung carcinomas [J].
Gugger, M ;
Burckhardt, E ;
Kappeler, A ;
Hirsiger, H ;
Laissue, JA ;
Mazzucchelli, L .
JOURNAL OF PATHOLOGY, 2002, 196 (04) :408-415
[10]  
HERBST RA, 1994, CANCER RES, V54, P3111