Alterations of p16/CDKN2, p53 and <i>ras</i> genes in oral squamous cell carcinomas and premalignant lesions

Makino, Hírofumi; Konishi, Noboru; Hiasa, Yoshio; Hayashi, Isao; Tsuzuki, Toshimitsu; Tao, Ming; Kitahori, Yoshiteru; Yoshioka, Nobutaka; Kirita, Tadaaki; Sugimura, Masahito

doi:10.1111/j.1600-0714.1996.tb01377.x

Cited by 44 publications

(33 citation statements)

References 31 publications

(4 reference statements)

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“…A prevalence of p16 alterations, ranging from 25% to 83%, has been reported in head and neck SCC [5,6,8,10,21,27,30]. The variable findings may be attributable to different patient populations and varying methodologies used for analysis.…”

Section: Discussionmentioning

confidence: 98%

p16 Alterations and retinoblastoma protein expression in squamous cell carcinoma and neighboring dysplasia from the upper aerodigestive tract

et al. 2001

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The progression potential of preinvasive epithelial lesions is usually evaluated by assessing the degree of histologic dysplasia. We examined p16, retinoblastoma protein (pRb), and proliferating cell nuclear antigen (PCNA) immunophenotypes in 57 cases of previously untreated squamous cell carcinoma (SCC) of the upper digestive tract and in the neighboring normal and dysplastic epithelia. Tissue samples were examined for homozygous deletion of exon 2 of the p16 gene using polymerase chain reaction (PCR) analysis. The PCNA index increased with increasing grade of dysplasia. The pRb protein was expressed in 89% of the samples of SCCs and in the neighboring dysplasias and carcinoma in situ (CIS). In cases with a lack of pRb expression, corresponding preinvasive lesions were also negative. Lack of p16 expression was found in 82% of SCCs. The prevalence of p16 expression decreased with increasing grade of dysplasia. Molecular analysis of the p16 gene showed homozygous deletion in 37% of SCCs, 33% of CIS, and 15% of the samples of normal epithelia. Our data indicate that inactivation of p16 may play an important role in early head and neck carcinogenesis, whereas the mutation of Rb may be an infrequent event. The p16 immunophenotype might be a biomarker for an increased risk of progression in squamous dysplasia.

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Section: Discussionmentioning

confidence: 98%

p16 Alterations and retinoblastoma protein expression in squamous cell carcinoma and neighboring dysplasia from the upper aerodigestive tract

et al. 2001

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“…Functional loss of tumor suppressor genes is supposed to be one of the most common genetic alterations in the oral carcinogenesis. 13,15,17 El-Naggar et al showed that the most likely chromosomal region associated with early development of head and neck squamous carcinoma was 9p21. 12 In recent studies, 9p and/or 3p were reported as the essential step in head and neck carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Accumulative increase of loss of heterozygosity from leukoplakia to foci of early cancerization in leukoplakia of the oral cavity

Jiang

Fujii

Shirai

et al. 2001

Cancer

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“…The histology of advanced colonic cancers could not be divided into the tow types, although K-ras point mutations frequently occurred in the former and rarely in the latter [24]. K-ras point mutations have been shown to be less frequent in oral SCCs [25,26].…”

Section: Discussionmentioning

confidence: 99%

Expression of Minichromosome Maintenance 2 (MCM2), Ki-67, and Cell-Cycle-Related Molecules, and Apoptosis in the Normal-Dysplasia-Carcinoma Sequence of the Oral Mucosa

Kodani

Shomori²,

Osaki³

et al. 2001

Pathobiology

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Objective: We examined cell cycle and cell death biomarker trends with the normal-dysplasia-carcinoma sequence of the oral epithelia analyzing the pathological significance of a new biomarker, minichromosome maintenance 2 (MCM2). Methods: This study analyzed 12 patients with normal oral epithelia, 69 with dysplasia, and 35 with squamous cell carcinoma (SCC); in 13 patients, SCCs were preceded by dysplasia. The sections were immunostained for MCM2, Ki-67, P53, P27^Kip1 and P21^CIP1/WAF1, and conducted by TUNEL methods. Western blot analysis of MCM2 was performed in the 4 human cultured oral SCCs, all of which showed the expression. Results: Significantly higher labeling indices (LI; %) of MCM2, Ki-67, and P53, as well as lower LI of TUNEL indices (TI; %), P27, and P21 were noted in the SCCs than in the dysplasias. The 13 dysplasias developed SCC with significantly higher LI of MCM2 and P53, and lower LI of P21 than the other dysplasias (each p < 0.05). The LI of MCM2, P21 and the TI were not correlated with P53 expression. Conclusions: Oral dysplasia was characterized by lower cell proliferation and a higher frequency of cell death compared to SCCs. The higher LI of MCM2 and P53 and the lower LI of P21 might predict malignant transformation of oral dysplasia. MCM2 is regulated via a P53-independent pathway, and a useful biomarker of proliferating cells.

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Alterations of p16/CDKN2, p53 and ras genes in oral squamous cell carcinomas and premalignant lesions

Cited by 44 publications

References 31 publications

p16 Alterations and retinoblastoma protein expression in squamous cell carcinoma and neighboring dysplasia from the upper aerodigestive tract

p16 Alterations and retinoblastoma protein expression in squamous cell carcinoma and neighboring dysplasia from the upper aerodigestive tract

Accumulative increase of loss of heterozygosity from leukoplakia to foci of early cancerization in leukoplakia of the oral cavity

Expression of Minichromosome Maintenance 2 (MCM2), Ki-67, and Cell-Cycle-Related Molecules, and Apoptosis in the Normal-Dysplasia-Carcinoma Sequence of the Oral Mucosa

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