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Titolo:
IMMUNOHISTOCHEMICAL AND MOLECULAR EVALUATION OF THE MDM-2 GENE-PRODUCT IN BRONCHOGENIC-CARCINOMA
Autore:
GORGOULIS VG; RASSIDAKIS GZ; KARAMERIS AM; PAPASTAMATIOU H; TRIGIDOU R; VESLEMES M; RASSIDAKIS AN; KITTAS C;
Indirizzi:
53 ANTAIOU STR,LAMPRINI ANO PATISIA GR-11146 ATHENS GREECE UNIV ATHENS,SCH MED,DEPT HISTOL & EMBRYOL GR-11527 ATHENS GREECE UNIV ATHENS,SCH MED,DEPT PULM MED GR-11527 ATHENS GREECE 401 ARMY GEN HOSP,DEPT PATHOL ATHENS GREECE SOTIRIA HOSP,DEPT PATHOL ATHENS GREECE
Titolo Testata:
Modern pathology
fascicolo: 5, volume: 9, anno: 1996,
pagine: 544 - 554
SICI:
0893-3952(1996)9:5<544:IAMEOT>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR SUPPRESSOR GENE; LUNG-CANCER; P53 MUTATIONS; WILD-TYPE; AMPLIFICATION; ONCOGENE; PROTEIN; POLYMORPHISMS; EXPRESSION; SARCOMAS;
Keywords:
DIFFERENTIAL PCR; IMMUNOHISTOCHEMISTRY; LUNG CARCINOMA; MDM-2 PROTEIN; NORTHERN BLOT; P53 PROTEIN; SSCP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
64
Recensione:
Indirizzi per estratti:
Citazione:
V.G. Gorgoulis et al., "IMMUNOHISTOCHEMICAL AND MOLECULAR EVALUATION OF THE MDM-2 GENE-PRODUCT IN BRONCHOGENIC-CARCINOMA", Modern pathology, 9(5), 1996, pp. 544-554

Abstract

In this study, we investigated immunohistochemically the expression of mdm-2 protein in 93 surgically resected bronchogenic carcinomas. Thefindings were correlated with p53 protein detection status and clinicopathologic data (histologic type, differentiation grade of the lesions, lymph node metastases, and smoking history of the patients), Thirtyof the 93 immunohistochemically examined specimens were subjected to Northern blot and differential polymerase chain reaction analysis to look into the mechanism of mdm-2 overexpression. Finally, we studied the concordance between p53 immunohistochemical positivity and p53 gene alterations as assessed by the single-strand conformation polymorphismtechnique. Seventy-three (78%) and 67 (72%) of 93 carcinomas showed nuclear immunoreactivity for mdm-2 and p53 proteins, respectively. We observed a high degree of concordance (75%) between p53 mutations and p53 immunolabelling, which was even higher in the specimens with p53 positivity in more than 50% of the cells (90%). Despite the high percentage of mdm-2 and p53 expression, the two molecules were simultaneouslydetected in 50 (54%) of 93 cases. Forty-two (84%) of the 50 cases were accompanied by p53 mobility shifts, which indicated mutations, Interestingly, statistical analysis revealed an almost significant correlation between the carcinomas with mdm-2/p53 coexpression and lymph node disease (P = 0.058), which indicated a possible ''gain of function'' phenotype. In addition, absence of reactivity for both proteins was statistically more frequent in the patients without lymph node disease (P= 0.006). The mdm-2-positive/p53-negative immunohistochemical profilewas more often seen in adenocarcinomas (P = 0.003), especially in well-differentiated ones (P = 0.02), than in other histologic types of lung cancer, which suggested a p53-independent pathway of mdm-2 overexpression. Molecular analysis showed that mdm-2 overexpression was a consequence of increased transcription rather than of mdm-2 gene amplification. The smoking history of the patients was strongly related to p53 (P = 10(-4)) even in the group of adenocarcinomas (P = 0.012). No correlation was observed between cigarette consumption and mdm-2 immunoreactivity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/08/20 alle ore 07:03:58