High Frequency of Allelic Loss in Dysplastic Lichenoid Lesions

Abstract

SUMMARY:Oral lichen planus (OLP) is a common mucosal condition that is considered premalignant by some, whereas others argue that only lichenoid lesions with epithelial dysplasia are at risk of progressing into oral carcinoma. A recent study from this laboratory used microsatellite analysis to evaluate OLP for loss of heterozygosity (LOH) at loci on three chromosomal arms (3p, 9p, and 17p) (Am J Path 1997;Vol151:Page323-Page327). Loss on these arms is a common event in oral epithelial dysplasia and has been associated with risk of progression of oral leukoplakia to cancer. The data showed that, although dysplastic epithelium demonstrated a high frequency of LOH (40% for mild dysplasia), a significantly lower frequency of LOH was noted in OLP (6%), which is even lower than that in hyperplasia (14%). Such results do not support OLP as a lesion at risk for malignant transformation. As a second step of the research, we determined LOH frequencies in 61 dysplastic lichenoid lesions (mild 35; moderate 19; severe 7) using the same microsatellite markers and compared these results with data obtained from the first study and from 13 normal mucosal specimens. Dysplastic lichenoid lesions showed a high frequency of loss (54% for lichenoid lesions with mild dysplasia), but values did not differ significantly from those observed in dysplasia of similar degree without lichenoid appearance. None of the normal mucosa demonstrated LOH. Epithelial dysplasia is a sign of malignant risk, independent of lichenoid changes. Such results suggest that pathologists should search for dysplasia carefully in lesions that otherwise qualify as OLP and that caution should be used when discounting dysplasia as being merely a reactive condition in lichenoid lesions. (Lab Invest 2000, 80:233-237).

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.…”

Epidemiologic Trends in Head and Neck Cancer and Aids in Diagnosis

“…Oral epithelial dysplasias (lichenoid dysplasia) may exhibit a chronic inflammatory cell infiltrate consisting of mostly lymphocytes that resembles the chronic inflammation seen in lichen planus, however has accompanying epithelial cellular alterations consistent with dysplasia as noted in Table 4 36, 37 . Moreover, the plaque variant of lichen planus and PVL may also share similar clinical and microscopic features, leading to a misdiagnosis of lichen planus 32 .…”

Overexpression of LRP12, a gene contained within an 8q22 amplicon identified by high-resolution array CGH analysis of oral squamous cell carcinomas

“…Dysplastic, tumor and adjacent stromal cells were microdissected from hematoxylin-and eosin-stained sections LRP12 overexpression in oral squamous cell carcinoma C Garnis et al and DNA was isolated as described previously (Zhang et al, 1997). Samples for gene expression analysis were collected within 15 min of surgery and frozen in liquid nitrogen.…”

“…Microsatellite analysis was performed to detect LOH/AI in specific chromosomal regions according to published protocols (Zhang et al, 1997). For comparison, the underlying stroma was used as a source of matched control DNA.…”