p53 Gene Mutations in Human Skin Cancers and Precancerous Lesions: Comparison with Immunohistochemical Analysis

Kubo, Yoshiaki; Urano, Yoshio; Yoshimoto, Katsuhiko; Iwahana, Hiroyuki; Fukuhara, Kazunobu; Arase, Seiji; Itakura, Mitsuo

doi:10.1111/1523-1747.ep12373002

Cited by 119 publications

(66 citation statements)

References 22 publications

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“…there is a pronounced discordance between p53 mutation and p53 immunohistochemical overexpression. This confinns some earlier findings in HNSCC (Xu et al 1994;Nylander et al 1995) and in skin cancers (Kubo et al, 1994). but contradicts others (Ahomadegbe et al, 1995).…”

Section: Discussionsupporting

confidence: 63%

p53 mutation, but not p53 overexpression, correlates with survival in head and neck squamous cell carcinoma

Mineta

Borg²,

Dictor³

et al. 1998

Br J Cancer

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Summary Survival in squamous cell carcinoma of the head and neck (HNSCC) was compared with overexpression and mutation of the p53 gene. Archival tissue from 77 tumours was analysed for protein expression using immunohistochemistry (IHC) with the monoclonal antibody Do-7, and for the presence of mutation in exons 5-8 using single-stranded conformation polymorphism (SSCP), followed (4/19) or low protein expression (4/33). Fifty-eight patients were eligible for survival analysis. There was a strong correlation between p53 mutation and cause-specific survival; median survival among mutated cases was 12.5 months compared with >160 months among non-mutated patients (P < 0.005). There was no correlation between p53 overexpression and survival. The results suggest that p53 mutation status is an important prognostic factor in HNSCC, and that IHC analysis of protein overexpression is an inadequate measure of gene mutation in these tumours.

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Section: Discussionsupporting

confidence: 63%

p53 mutation, but not p53 overexpression, correlates with survival in head and neck squamous cell carcinoma

Mineta

Borg²,

Dictor³

et al. 1998

Br J Cancer

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“…Mutation studies of p53 gene confirm a higher incidence of mutations in squamous cell carcinoma, in contrast to keratoacanthoma. 25,26 They found no correlation between immunohistochemical detection of p53 oncoprotein and gene mutations, and recommend sequence analysis to determine gene mutation. From the above studies, it appears that although immunohistochemical determination is helpful, sequence analysis of p53 gene is essential to identify the mutation.…”

Section: Discussionmentioning

confidence: 98%

“…7,8 Mutation studies of the p53 gene confirm a higher incidence of mutations in squamous cell carcinoma, in contrast to keratoacanthoma. 25,26 Materials and methods A total of 17 cases of well to moderately differentiated cutaneous squamous cell carcinoma and 24 early phase keratoacanthoma were retrieved from the files of National University Hospital Pathology Department. Poorly differentiated squamous cell carcinomas were excluded from the study, as they posed little diagnostic problems in distinguishing from keratoacanthoma.…”

mentioning

confidence: 99%

Biological behavior of keratoacanthoma and squamous cell carcinoma: telomerase activity and COX-2 as potential markers

2004

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Distinguishing keratoacanthoma from squamous cell carcinoma is a persistent issue in pathology practice. Solitary keratoacanthoma is a self-limiting lesion as opposed to rather aggressive clinical behavior of squamous cell carcinoma. Several markers were studied to understand their biology and to separate these two lesions on a firm basis, but without much success. In this study, we plan to utilize recent markers such as telomerase activity and cyclooxygenase-2 (COX-2) along with more established marker p53 in understanding the biologic differences between keratoacanthoma and squamous cell carcinoma. We studied 17 well to moderately differentiated squamous cell carcinoma and 24 early proliferative phase keratoacanthoma by immunohistochemistry for the expression of p53 protein, COX-2 and telomerase activity. Higher telomerase activity was found in 11/17 squamous cell carcinoma (65%) compared to 4/24 (17%) of keratoacanthoma. Similarly, stronger expression of p53 and COX-2 was detected in 12 (71%) and 11 (65%) cases of squamous cell carcinoma compared to 2 (8%) and 2 (8%) cases of keratoacanthoma respectively. A highly significant 'P ' value was obtained for telomerase activity (0.001), p53 (0.000), and COX-2 (0.001). Telomerase activity, COX-2, and p53 expression provide evidence that keratoacanthoma and squamous cell carcinoma are indeed distinct entities and also help in discriminating these two lesions, which closely resemble each other on conventional morphology. Although these markers present new insights into the biologic variation of keratoacanthoma and squamous cell carcinoma, they are of limited value for routine application in histological distinction of these two lesions. The differential expression of markers also explains the sustained proliferation observed in squamous cell carcinoma, compared to a shorter lifespan and involution in keratoacanthoma.

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“…CC to TT or C to T transitions at dipyrimidine sites (Brash et al, 1991(Brash et al, , 1996Kress et al, 1992). Reported prevalence of p53 mutations in BCC di ers from 10 ± 60% (Brash et al, 1991;Campbell et al, 1993;Kubo et al, 1994;Rady et al, 1992), however the signi®cance of p53 gene mutations in BCC remains unsolved. Are p53 gene mutations essential for BCC development and growth or are they merely markers of clonally expanding tumor cells?…”

Section: Introductionmentioning

confidence: 99%

Molecular pathology in basal cell cancer with p53 as a genetic marker

et al. 1997

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Human basal cell cancer (BCC) has unique growth characteristics with virtual inability to metastasize. We investigated clonality and genetic progression using p53 mutations as marker. Sampling was done through microdissection of frozen immunohistochemically stained 16 mm slices of tumors. From 11 BCC tumors 78 samples were analysed. Direct DNA sequencing of exons 5 ± 8 was performed, haplotypes were determined after cloning of p53 exons and loss of heterozygosity (LOH) ascertained by microsatellite analysis. All tumors had p53 mutations and in a majority both p53 alleles were a ected, commonly through missense mutations. Microdissection of small parts (50 ± 100 cells) of individual tumors showed BCC to be composed of a dominant cell clone and prone to genetic progression with appearance of subclones with a second and even third p53 mutation. Samples from normal immunohistochemically negative epidermis always showed wild type sequence, except for a case of previously unknown germline p53 mutation. Our analysis also included p53 immunoreactive patches i.e. morphologically normal epidermis with a compact pattern of p53 immunoreactivity. Mutations within those were never the same as in the adjacent BCC. This detailed study of only one gene thus uncovered a remarkable heterogeneity within a tumor category famous for its benign clinical behavior.

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p53 Gene Mutations in Human Skin Cancers and Precancerous Lesions: Comparison with Immunohistochemical Analysis

Cited by 119 publications

References 22 publications

p53 mutation, but not p53 overexpression, correlates with survival in head and neck squamous cell carcinoma

p53 mutation, but not p53 overexpression, correlates with survival in head and neck squamous cell carcinoma

Biological behavior of keratoacanthoma and squamous cell carcinoma: telomerase activity and COX-2 as potential markers

Molecular pathology in basal cell cancer with p53 as a genetic marker

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