Loss of heterozygosity analysis of keratoacanthoma reveals multiple differences from cutaneous squamous cell carcinoma.

AJ Waring,JL Rees,M Takata,I Rehman

doi:10.1038/bjc.1996.113

Abstract

Keratoacanthomas (KAs) resemble squamous cell carcinomas (SCCs) except that, unlike SCCs, after a period of rapid growth over a few months they involute completely. The basis of their regressing natural history is not known. We have examined keratoacanthomas and another benign cutaneous tumour, the basal cell papilloma (BCP), for loss of heterozygosity (LOH) at a number of loci that are frequently lost in SCCs and other skin tumours. The frequency of LOH for both KAs and BCPs was low, with only isolated losses identified at 9p, 9q and 10q in KAs [fractional allelic loss (FAL) was 1.3%], and at 9p and 17p in BCPs (FAL was 0.4%). This contrasts with previous work showing a FAL of 32% in SCC and 46% in actinic keratoses. The results show a clear difference between KA and SCC and do not support the hypothesis that KAs are SCCs that regress as a result of external (host) influences but rather suggest that KAs and SCCs are different de novo. LOH around the locus implicated in the multiple self-healing epitheliomata of Ferguson-Smith (9q22-q31) was shown in only 1 of 11 KAs.

Highlights

Current cellular theories of carcinogenesis emphasise the multistage nature of cancer in which there is thought to be a causal relation between the accumulation of genetic abnormalities and the clinical and biological behaviour of the tumour (Weinberg, 1991; Fearon and Vogelstein, 1990; Yokota and Sugimura, 1993)
Twenty-four archival blocks with a diagnosis of sporadic KA and 27 blocks with a diagnosis of basal cell papilloma were retrieved for analysis from the Royal Victoria Infirmary, Newcastle upon Tyne
Tumour DNA and DNA from normal adjacent skin was isolated according to standard methods by proteinase K digestion and phenol - chloroform extraction (Jackson et al, 1992). (FAL) is given by summing the loss of heterozygosity (LOH) score at all loci and dividing by the number of tumours examined that were informative at the loci

Summary

Introduction

Current cellular theories of carcinogenesis emphasise the multistage nature of cancer in which there is thought to be a causal relation between the accumulation of genetic abnormalities and the clinical and biological behaviour of the tumour (Weinberg, 1991; Fearon and Vogelstein, 1990; Yokota and Sugimura, 1993). The occurrence of a range of different tumour types, all keratinocyte derived and related to ultraviolet radiation (UVR), with markedly different clinical behaviours, and in particular the presence of a number of neoplastic lesions, such as keratoacanthomas (KAs), that show spontaneous regression are of considerable experimental interest (Rees, 1994). KAs are a common keratinising squamous neoplasm, classically occurring on the JVR-exposed skin of elderly individuals, which are characterised clinically by a period of rapid growth over a 4-12 week period followed by spontaneous involution (Schwartz, 1994; Straka and GrantKels, 1991; Ghadially and Ghadially, 1993). A number of pathogenic abnormalities have been described in KAs, including H-ras mutations, aneuploidy, altered p53 immunostaining and the presence of human papillomavirus (HPV) DNA (Corominas et al, 1989; Newton et al, 1987; Herzberg et al, 1991; Kerschmann et al, 1994; Stephenson et al, 1992; Lee and Teh, 1994; Schwartz, 1994)

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