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

BACKGROUND: Oral leukoplakia is a premalignant lesion, but the genetic changes in the foci of early cancerization in leukoplakia have not been studied. METHODS: Loss of heterozygosity (LOH) was successively investigated in 13 cases in the leukoplakia and foci of early cancerization in the same leukoplakia. The authors microdissected both lesions, and 33 microsatellite markers at 14 chromosomal loci were examined by a polymerase chain reaction-based microsatellite assay. RESULTS: Loss of heterozygosity detected in the leukoplakia was identically observed in the foci of early cancerization in leukoplakia in 11 of 13 cases, and in 2 cases allelic divergence was observed. Loss of heterozygosity occurred even in the leukoplakia with high frequency at 9p21 (66.7%), 3p14-25 (61.5%), 4q31-32 (45.5%), and 17p12-14 (44.4%). The foci of early cancerization in leukoplakia showed accumulative increase of LOH at these and other loci. Loss of heterozygosity at 5q21-23 was found to have significant difference between the leukoplakia and the foci of early cancerization in leukoplakia (P = 0.0137, Fisher exact test). Microsatellite instability was observed at low level in three cases. The mean value of fractional allelic loss in the leukoplakia differed significantly from that in the foci of early cancerization in leukoplakia (0.02 < P < 0.05, Student t test). CONCLUSIONS: The high incidence of LOH in the leukoplakia indicated premalignant potentiality of this lesion and that accumulative increase of LOH from leukoplakia to foci of early cancerization in leukoplakia might play a significant role in the cancerization of leukoplakia. Comparison of LOH between the leukoplakia and the foci of early cancerization in leukoplakia suggested that these two lesions were derived from a common clone.

Immunohistochemical study of oral lichen planus associated with hepatitis C virus infection, oral lichenoid contact sensitivity reaction and idiopathic oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is a common mucocutaneous disorder and might be associated to a possible pathogenic relationship with hepatitis C virus (HCV) infection or hypersensitivity to dental alloy. We examined the clinical and immunohistochemical features of OLP associated with HCV infection (OLP-HCV), oral lichenoid contact sensitivity reaction (OLCSR), and idiopathic oral lichen planus (iOLP). The immunohistochemical expressions of CD4, CD8, B cells, Class II major histocompatibility complex antigen (HLA-DR), S-100, HSP60, Proliferating cell nuclear antigen (PCNA) and Ki-67 were compared to study the pathogenic differences of the three OLP groups. MATERIALS AND METHODS: Three groups of OLP patients, (I) OLP-HCV patients (n = 17), (2) OLCSR patients (n = 10) and (3) iOLP patients (n = 14) were retrieved from clinical records and tissues examined immunohistochemically by the avidin-biotin-complex technique. RESULTS: The patients with OLP-HCV showed widespread lesions. The proportion of CD8+ cells was found to be significantly higher in the lamina propria of the OLP-HCV patients and a significantly lower proportion of CD8+ cells of the OLCSR patients was noticed in the epithelium or the connective tissue papillae than in the iOLP patients. There were no significant differences in either the number of CD4+ cells or B cells between the three OLP groups. No significant differences in the number of HLA-DR+ cells were found between the three OLP groups and some OLP-HCV patients showed a significant increase of S-100+ cells in the epithelium compared with iOLP patients. There were no significant differences in either the number of PCNA+ or Ki-67+ cells between the groups. The patients showed similar weak expressions of HSP60 in the three OLP groups. CONCLUSION: The different distributions of the CD8+ cells that could have functionally different roles might be related to the distinct pathogenic mechanisms in the three OLP groups.

Dejerine-sottas disease with a novel de novo dominant mutation, Ser 149 Arg, of the peripheral myelin protein 22.

The Ser149Arg mutation of peripheral myelin protein 22 (PMP22) was found in a 19-year-old woman with a sporadic case of Dejerine-Sottas disease. The patient showed delayed motor development. She walked for the first time with support at the age of 2 years. Scoliosis developed at age 4 years. Her walking ability was best at age 11. Thereafter, she showed progressive muscle weakness and sensory disturbances in the distal extremities. At the age of 18 years, the use of a wheelchair became necessary. Motor and sensory nerve conduction studies showed absent motor and sensory responses on electrical stimulation of the limb nerves. A sural nerve biopsy specimen showed marked decreases in the numbers of both large and small myelinated fibers, abundant onion-bulb formation, and hypomyelination. Electron microscopic observation revealed the presence of demyelinated axons and myelin sheaths disproportionately thin relative to axon diameter. That this was a de novo mutation was established by parentage testing and PMP22 gene analysis of the parents. The mutation seems to be novel and dominant.

Heterogeneity in the gingival fibromatoses.

Forty-nine cases of isolated familial and idiopathic gingival fibromatoses, consisting of 12 cases from six families and 37 cases of idiopathic gingival fibromatosis, were reviewed. Pedigrees of five families revealed various penetrances and genetic heterogeneity as suggested by the presence of both autosomal dominant and autosomal recessive inheritances. Ultrastructurally, the lesions were composed of fibroblast-like cells and myofibroblast-like cells, with the former being the predominant cell type. The 267 cases of familial and idiopathic gingival fibromatoses were analyzed, and they with or without hypertrichosis, mental retardation, and/or epilepsy. These included 49 cases seen by the authors, 50 cases from the Japanese literature, and 168 cases from non-Japanese literature. Isolated gingival fibromatosis occurred more frequently after age of 12 years (P less than 0.0074). There was no significant difference in age of onset between generalized and localized forms of the idiopathic gingival fibromatosis. Gingival fibromatosis with hypertrichosis and mental retardation and/or epilepsy occurred frequently before 12 years (P less than 0.069). It has been shown that heterogeneity of the gingival fibromatosis is a result of either histologic heterogeneity, genetic heterogeneity, or a combination with other systemic disorders.

[Familial gingival fibromatosis: report of a case].

One family of familial gingival fibromatosis was presented. Case 1 is an 11 years old girl. Gingival fibromatosis was noted by delayed eruption of permanent teeth. Fibromatosis was seen in whole gingiva and lower 1/2 to 1/3 of the tooth crowns was covered. Gingivectomy was performed. Case 2 was 42 years old man, who was father of case 1. Firstly gingival swelling was noted at the age of 10 years. He had operations of gingivectomy at the age of 28 years. It recurred and fibromatosis was seen in whole gingiva and lower 1/2 to 1/3 of the tooth crowns was covered. Cytogenetically no abnormality was seen in the chromosomes of both cases. Reported cases of familial and non-familial gingival fibromatosis in Japan were reviewed.

[Observation on calcification of necrotic tissue in pressure side of periodontal membrane incident to experimental tooth movement].

In an orthodontic point of view, it is said that necrotic tissues cause a standstill of tooth movement until they disappear and that term of the standstill is related to the size of the necrotic tissues. Although remodeling processes of a periodontal membrane in compressed area were reported as series of phenomena like degeneration, coagulative necrosis, calcification and histiolysis, there is no direct evidence that the necrotic tissue is really calcified. The purpose of this study is to clarify histologically whether the necrotic tissues in the periodontal membrane are calcified or not and to know when appearance and disappearance of the calcification occur during an experimental tooth movement. Twenty eight rats were used for this study. For the experimental tooth movement, the orthodontic elastics were inserted into the interproximal space between the maxillary right 1st and 2nd molars during 1, 2, 3, 5, 7 and 14 days respectively (Waldo's method). The periodontal tissues were observed on undecalcified sections by vital staining in which oxytetracycline (3 mg/kg), alizarin red (8 mg/kg) and calcein (0.8 mg/kg) were applied as well as by contact micro radiography (CMR). Findings were as follows: 1) After 2 days of tooth movement, a part of the periodontal membrane in compressed area showed fluorescence by vital staining and was radiopaque by CMR. This means that the necrotic tissues are really calcified at least after 2 days of experimental tooth movement. 2) After 7-14 days no calcified tissue could be found in the periodontal membrane. The calcified tissues may disappear under processes of resorption in this area.(ABSTRACT TRUNCATED AT 250 WORDS)