p53 expression in normal, dysplastic, and neoplastic laryngeal epithelium. Absence of a correlation with prognostic factors

Nadal, Alfons; Campo, Elı́as; Pinto, J.A.; Mallofré, Carme; Palacı́n, Antonio; Arias, Carlos; Traserra, J; Cardesa, Antonio

doi:10.1002/path.1711750205

Cited by 58 publications

(45 citation statements)

References 23 publications

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“…However, there is no objecti ve evidence of a correlation between p53 expression and prognostic factors for head and neck carcinomas. 27 The absence of a correlation between the expression of p53 in the normal adjacent lTIUCOSa and in the tumor area of the same patients detected here agrees with literature data. Nees et £11.…”

Section: Allele Of Gene P53 Are ---------------------------------supporting

confidence: 92%

P53 overexpression in epidermoid carcinoma of the head and neck

Logullo¹,

Kowalski²,

Nonogaki³

et al. 1997

Sao Paulo Med. J.

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The theory of field cancerization in tumors of the head and neck reflects the complex oncogenesis that occurs in this region. The mechanisms that control cell proliferation at the molecular levei in epidermoid carcinomas (ECs) of the upper aerodigestive tract are still unclear. Mutations in p53 are the genetic alterations most often detected in ECs of the head and neck and seem to contribute actively to the carcinogenic process triggered by p53 as a tumor-suppressor gene and to its association with tobacco. The objective of the present study was to investigate the expression of p53 protein in epidermoid head and neck carcinomas by immunohistochemistry and its immunohistochemical correlation with other prognostic factors. The study was conducted on 63 consecutive ECs cases not submitted to previous treatment. Specimens of the tumor and of the normal adjacent mucosa were collected during surgery and submitted to immunohistochemical reaction for the determination of the expression of anti-protein p53 antibody (M7001 DAKO AIS, Denmark). Anatomo-c1inical and demographic data were not significantly correlated with the presence of Iymph node metastases or p53 expression in the tumor or in the adjacent normal mucosa. Tumor localization in the larynx was significantly correlated with p53 expression. Histological grading as grades I, 11, 111 and IV was correlated with significant p53 expression (p = 0.025). Conclusions: 1) in the studied material obtained from 63 cases of head and neck ECs, we detected a 48 percent rate of immunohistochemically detectable p53 overexpression; 2) we did not detect a relationship between demographic patient data and p53 expression in the tumor or in the normal adjacent mucosa; 3) p53 overexpression was significantly more frequent in ECs material from the larynx; and 4) The presence of 12 cases with p53 overexpression in the normal adjacent mucosa and with a p53-negative tumor is in agreement with the theory of field cancerization. Follow-up of this patient series for a longe r period of time will permit a better analysis of these values. UNITERMS: P53, squamous cell carcinoma, head and neck cancer, immunohistochemistry INTRODUCTION E Pidermoid carcinomas (ECs) represent more than 90 percent of the neoplasias of the upper aerodigestive trace) and their incidence increases among subjects who smoke cigarettes and consume alcoholic beverages. 12ECs correspond to the sixth most frequent form of cancer in the worldY

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Section: Allele Of Gene P53 Are ---------------------------------supporting

confidence: 92%

P53 overexpression in epidermoid carcinoma of the head and neck

Logullo¹,

Kowalski²,

Nonogaki³

et al. 1997

Sao Paulo Med. J.

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“…The molecular alterations leading to the development and progression of these carcinomas remain unclear. Several genetic studies have identi®ed p53 gene mutations and protein overexpression as early events in the development of SCC of the upper respiratory tract and lung (Dolcetti et al, 1992;Nadal et al, 1995). Additionally, we and others have recently shown that deregulation of cyclin D1 by gene ampli®cation and overexpression is associated with advanced stages and poor prognostic evolution of laryngeal carcinomas (Jares et al, 1994;Meredith et al, 1995;Michalides et al, 1995).…”

Section: Introductionmentioning

confidence: 94%

p16MTS1/CDK4I mutations and concomitant loss of heterozygosity at 9p21-23 are frequent events in squamous cell carcinoma of the larynx

Jares

Fernández

Nadal³

et al. 1997

Oncogene

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We have examined the presence of p16 MTS1/CDK4I gene deletions, mutations and methylation status, and 9p21-23 deletions in a series of 46 squamous cell carcinomas of the larynx and paired normal mucosa previously characterized for cyclin D1 gene ampli®cation and overexpression. pRb expression was also examined by immunohistochemistry. p16 MTS1/CDK4I mutations were found in 10/46 (22%) carcinomas and hypermethylation in 2/31 (7%). Loss of heterozygosity at 9p21-23 was found in 24 out of 42 (57%) carcinomas examined. All p16 MTS1/CDK4I mutated cases and the two hypermethylated carcinomas showed 9p21-23 loss of heterozygosity. The loss of heterozygosity correlated with advanced local invasion (P=0.0045), lymph node metastases (P=0.0326), stage IV of the tumors (P=0.0058), and existence of cyclin D1 ampli®cation/overexpression (P<0.03). Only one out of 37 carcinomas was negative for pRb expression. No alterations in p16 gene or 9p21-23 loss of heterozygosity were detected in this case. These ®ndings indicate that p16 MTS1/CDK4I is frequently inactivated by gene mutation, hypermethylation, and allelic deletions in a signi®cant subset of squamous cell carcinomas of larynx. Since 9p21-23 loss of heterozygosity was more frequently detected than p16 MTS1/CDK4I mutations, and mutated carcinomas invariably had loss of heterozygosity, allelic losses probably precede the p16 MTS1/CDK4I mutations. Their association with cyclin D1 deregulation in advanced carcinomas could indicate a possible cooperative e ect in the progression of these neoplasms.

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“…It is therefore under-standable that numerous studies have been devoted to the progression of OIN to invasive SCC. The role of cell-cycle proteins such as p16, p21, p27, p53, cyclin D1 and E have been extensively studied over the last two decades (Shin et al 1994;Fraczek et al 2007;Gorgoulis et al 1994;Gale et al 1997;Dolcetti et al 1992;Barbatis et al 1995;Nadal et al 1995;Poljak et al 1996;Uhlman et al 1996;Hirai et al 2003;Ioachim et al 2004;Wayne&Robinson 2006). However, none of these markers has been found to have reliable predictive value.…”

Section: Additional Markers Of Malignant Alterations Of Oral Intraepimentioning

confidence: 99%