Tadamitsu Kameyama

Lichen planus and hepatitis C virus in the Northern Kyushu region of Japan

Abstract. Oral lichen planus (OLP) is a common oral disorder that manifests a mucosal reaction to a variety of aetiological factors, including liver disorder. This study investigated the relationship between OLP and hepatitis C virus (HCV) infection by studying the prevalence of hepatitis B and C virus infection or liver disease in 45 patients with OLP in the Northern Kyushu region of Japan where the prevalence of HCV infection is the highest in the country. Serum hepatitis B virus surface antigen (HBsAg) was positive in only four patients. Serum anti‐HCV or serum HCV RNA was positive in 28 (62%) and 27 (60%) of 45 OLP patients, respectively. The majority (35 of 45, 78%) of OLP patients suffered from liver disease, including chronic hepatitis C (22/45, 49%), HCV‐related liver cirrhosis (two), and HCV‐related hepatocellular carcinoma (two). These results suggest that HCV is a major cause of OLP.

Development and exacerbation of oral lichen planus during and after interferon therapy for hepatitis C

Oral lichen planus (OLP) is frequently seen in patients with hepatitis C virus (HCV) infection. To clarify the role of HCV in OLP pathogenesis, we investigated the occurrence and progression of oral lesions in chronic hepatitis C patients treated with interferon. Oral surgeons examined 24 hepatitis C patients (15 men, nine women; mean age 48.1 years) for oral lesions before, during and after interferon (IFN) treatment. OLP was observed in 16.7% (4/24). Two patients had OLP before treatment, one during and one after treatment. Those who developed OLP during or after treatment had neither improvement nor disappearance of OLP even when serum HCV RNA became negative. Leucoplakia was seen in four patients before treatment and oral cancer in one patient 6 months after completing treatment. OLP can occur, exacerbate and persist during IFN treatment for hepatitis C, even when serum HCV RNA becomes negative. The present study suggested that OLP pathogenesis in hepatitis C is due to host factors induced by HCV infection rather than direct HCV participation. Treating physicians should be aware of OLP occurrence or exacerbation by IFN treatment with hepatitis C patients, but IFN therapy is not necessarily contraindicated in these patients.

Expression of matrix metalloproteinase-3 in stage I and II squamous cell carcinoma of the oral cavity☆

PURPOSE The object of this study was to evaluate the significance of matrix metalloproteinase-3 (MMP-3) in tumor invasion and metastasis of early squamous cell carcinoma (SCC) of the oral cavity. MATERIALS AND METHODS Surgical specimens from 65 patients with stage I and II SCC of the oral cavity were the subjects of this study. Tissue specimens were fixed in formalin and embedded in paraffin, and the sections were stained with monospecific antibodies against human MMP-3 by the avidin-biotin-peroxidase complex method. RESULTS Of the 65 patients, 30 (46.2%) tested positive for MMP-3. Immunoreactivity revealed the expression of MMP-3 to be in the small cancer nests in the advancing front of invasion, but not in normal oral epithelium. MMP-3 expression was positively correlated with tumor size, depth of tumor invasion, diffuse invasive mode, and the high incidence of lymph node metastasis. CONCLUSION MMP-3-containing tumors will invade adjacent normal tissues more aggressively, including lymphatic and blood vessels. Therefore, the examination of MMP-3 expression in biopsy specimens should provide information useful in predicting the malignant potential of early SCC of the oral cavity.

Quantitative analysis of HCV RNA and genotype in patients with chronic hepatitis C accompanied by oral lichen planus.

Lichen planus (LP) is a common oral disorder that may represent a mucosal reaction to a variety of factors, including hepatitis C virus (HCV). To determine whether viral factors play a role in oral lichen planus (OLP) pathogenesis, we measured serum HCV RNA and determined HCV genotype in patients with chronic hepatitis C accompanied by OLP. The subjects included 43 patients with chronic hepatitis C: 23 with OLP (group 1) and 20 without OLP (group 2). Serum was collected from all subjects and used to quantify HCV RNA by the branched DNA signal amplification assay; HCV genotypes were classified by the reverse transcription–polymerase chain reaction (RT–PCR) method into types I, II, III and IV. Comparison of patient characteristics disclosed that the mean age of group 1, 60.7 years, was significantly higher (P=0.001) than that of group 2 (46.4 years). No significant differences were seen between sexes in values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein (T protein), albumin and gamma‐globulin. There were also no significant differences in HCV RNA levels or HCV genotypes between groups. The findings suggested that OLP pathogenesis was a result of host factors rather than viral factors.

The Significance of Epidermal Growth Factor Receptor and Matrix Metalloproteinase-3 in Squamous Cell Carcinoma of the Oral Cavity

Surgical specimens from 65 patients with squamous cell carcinoma (SCC) of the oral cavity were examined immunohistochemically. The clinicopathological significance of the expression of epidermal growth factor receptor (EGFR) and matrix metalloproteinase-3 (MMP-3) was assessed. Among the 65 tumours, 20(30.8%) and 37(56.9%) tested positively for EGFR and MMP-3, respectively. A positive correlation between the expression of EGFR and MMP-3 was found. The expression of EGFR in oral SCCs was associated with an advanced T stage of the primary tumour, an advanced pathological stage, and a high incidence of neck metastasis. In addition, MMP-3 was primarily expressed at the advancing front of cancer with a diffuse invasive mode. Thus, overexpression of MMP-3 was associated with an advanced pathological stage, a diffuse invasive mode, and a high incidence of neck metastasis. The analysis of MMP-3 expression is useful to evaluate the pathological status of tumours. Because EGFR-overexpressed tumour should produce larger amounts of MMP-3 in vivo, a close examination of oral SCC for expression of EGFR and MMP-3 should be helpful to predict their malignant potential.

Hepatitis C virus RNA detection in oral lichen planus tissue.

To the Editor:Hepatitis C virus (HCV) infection not only causes chronic liver diseases but has extrahepatic manifestations (1–3). Oral lichen planus (OLP) is frequently seen in patients with HCV infection (4). To elucidate a direct relationship between OLP and HCV infection, we investigated the existence of HCV RNA in 19 OLP tissues from subjects with and without antibody to HCV. A sensitive reverse transcription polymerase chain reaction detected HCV RNA in 13 of 14 tissues from antibody positive patients (Table 1). Positive and negative HCV RNA strands were observed in 13 (92.9%) and 3 (21.4%) tissues, respectively. On the other hand, neither positive or negative strands were present in OLP tissue from those HCV antibody negative. These results indicate that HCV persists and replicates in OLP lesions, suggesting a pathological role of HCV in OLP.

Effectiveness of glycyrrhizin for oral lichen planus in patients with chronic HCV infection.

Oral lichen planus (OLP), an intractable inflammatory disease characterized by a band-like lymphocytic invasion under the oral mucosa, is frequently associated with hepatitis C virus (HCV) infection. We investigated the effects of glycyrrhizin, which is used to treat chronic liver dysfunction, in nine patients with OLP who were positive for HCV antibody and HCV RNA. A control group, eight patients with OLP who were also positive for HCV antibody and HCV RNA, was given only dental cleaning. Glycyrrhizin (GL) was given intravenously, at a dose of 40ml (0.2% solution) daily, for 4 consecutive weeks. Six (66.7%) of the nine patients given GL improved clinically (P=0.0141 vs non-GL group), suggesting that GL is useful in treating OLP.

High incidence of oral precancerous lesions in a hyperendemic area of hepatitis C virus infection

Abstract We have investigated the incidence of oral precancerous lesions among the inhabitants in a hepatitis C virus (HCV) hyperendemic area. Two oral surgeons examined the oral lesions of 685 (295 men, 390 women; mean age of 56.1 years) adult inhabitants, hyperendemic area of HCV infection. All sera were examined for antibodies to HCV (anti-HCV) and serum HCV RNA. Anti-HCV or HCV RNA were detected in sera from 84 (12.3%) or 61 (8.9%) of all. Oral lichen planus (OLP), leukoedema, or leukoplakia were observed in 10 (1.5%), 82 (12%), or 47 (6.9%) subjects, respectively. The incidences of OLP, leukoedema, and leukoplakia in the subjects with HCV infection were significantly higher than those without HCV. These results indicated that HCV may play an important role in oral cancer and related precancerous lesions. Moreover, our study also emphasized the need for periodic examination of the oral cavity in patients with HCV.

Immunological evaluation in oral lichen planus with chronic hepatitis C

Oral lichen planus (OLP) is frequently associated with hepatitis C virus (HCV) infection. We have previously reported that the pathogenesis of OLP arises from host rather than viral factors. In this study, we investigated the role of these factors in 41 patients with chronic hepatitis C: 22 with OLP (group 1) and 19 without OLP (group 2). All patients had antibodies to HCV (anti-HCV) and were serum HCV RNA-positive; none were HBsAg-positive. Immune abnormalities in serum were evaluated by testing for antinuclear antibody (ANA), rheumatoid factor (RF) activity, immunoglobulins (IgG, IgM, and IgA), and cryoglobulin. The rate for ANA positivity and IgM levels were significantly higher in group 1 than in group 2 (P<0.05). Mean age in group 1 was significantly higher in group 2 (P=0.0001). Of the factors tested, ANA, IgM, and age, logistic regression showed that age correlated independently with OLP (P=0.003). In 5 patients in group 1, the infiltrating lymphocytic subsets of the OLP lesion were examined histopathologically. Predominant T cell infiltration was shown in all 5 patients. In addition to host factors, we also examined viral factors in both groups of patients, measuring serum HCV RNA level and determining HCV genotype. There were no significant differences between the groups in these viral factors. This study suggested that host factors induced by the HCV infection are more important than viral factors in the pathogenesis of OLP associated with hepatitis C.

Dentigerous cyst associated with a deciduous tooth. A case report.

A case of a dentigerous cyst associated with a deciduous tooth in a 2-year-old boy is presented. Radiologic examination revealed a well-defined radiolucency in the right maxilla associated with the crown of a maxillary second deciduous molar. The cyst cavity was lined with nonkeratinized squamous epithelium, and odontogenic epithelial islands were seen in subepithelial connective tissue.