Oral lichen planus has a high rate of TP53 mutations. A study of oral mucosa in Iceland

Abstract

Oral squamous cell carcinoma (OSCC) is a world-wide health problem. In addition to external exposure (smoking and alcohol), certain oral lesions may increase the risk of oral cancer (e.g. leukoplakia, erythroplakia, and oral lichen planus). TP53 has been implicated in OSCC, but there are limited studies of mutations in premalignant oral lesions. In this study, 55 samples from OSCC, 47 from hyperkeratotic (HK) oral mucosa, clinically diagnosed as white patches, 48 samples from oral lichen planus (OLP), and 12 biopsies from normal oral mucosa were studied immunohistochemically for expression of TP53 protein. From all the carcinoma samples and selected non-malignant samples showing moderate or strong TP53 protein expression, malignant cells or TP53-positive nuclei were microdissected and screened for mutations in exons 5-8 by constant denaturation gel electrophoresis. Moderate to strong TP53 protein staining was seen in 56% of OSCC, 32% of OLP but only in 13% of HK. All OLP samples showed a characteristic pattern of positive nuclei confined to the basal layer, whereas TP53 staining was seen in suprabasal nuclei in HK. Mutation rate was 11 out of 52 for OSCC, three out of 20 tested for HK and, remarkably, nine out 27 tested for OLP. There was no correlation between TP53 protein staining and TP53 mutations. No associations were found with anatomical sites or disease progression. The unexpectedly high mutation rate of OLP might explain the premalignant potential of this lesion.

Involvement of activation-induced cytidine deaminase in skin cancer development

“…A high rate of TP53 mutation was reported in lichen planus (60), consistent with the general notion that precancerous lesions have already accumulated somatic mutations. The fitness of cancer cells may be compromised because of excessive mutations if AID expression continues after full malignancy ("Muller's ratchet;" ref.…”

Molecular genetics of premalignant oral lesions

“…The increase in the number of p53 positive biopsies significantly correlates with the degree of dysplasia and loss of differentiation in OLP. Most OLP lesions have a characteristic pattern of p53 positive nuclei confined to the basal layer of the epithelium, and in one study, remarkably, nine out of 27 (33%) of the OLP lesions contained p53 mutations when screened for mutations in exons 5 through 8 (Ogmundsdottir et al , 2002).…”

Chromosomal Numerical Aberrations in Oral Lichen Planus

“…To uncover some of the molecular genetic aberrations associated with OLP, investigators have used molecular and genetic methods such as loss of heterozygosity (LOH) (Zhang et al, 2000), chromosome in situ hybridization (Kim et al, 2001), p53 and c-erbB2 expression (Girod et al, 1994(Girod et al, , 1995Kilpi et al, 1996;Ogmundsdottir et al, 2002), and telomerase activity (O'Flatharta et al, 2002). However, none of these methods appears to provide definitive predictive information with regard to the malignant potential of a lesion diagnosed as OLP.…”