Reactivity of monoclonal antibodies 17.13 and 63.12 with 141 oral mucosal lesions

We studied the reactivity of monoclonal antibodies (MAbs) 17.13 and 63.12 with normal and diseased human oral mucosa by means of the immunoperoxidase technique. The specimens included: 22 normal oral tissues, 20 benign tumors, 17 lichen planus, 23 focal keratosis and epithelial hyperplasias, 18 proliferative verrucous leukoplakias, 20 dysplasias, and 21 squamous cell carcinomas. In most cases of normal mucosa and benign lesions, MAb 17.13 stained basal epithelial cells only, whereas MAb 63.12 stained all cell layers above the basal cells. In the premalignant and malignant lesions MAb 17.13 stained above the basal cells and MAb 63.12 either stained areas not stained by MAb 17.13 or the staining was absent. Based on the different staining patterns observed, there appears to be a potential value of these new reagents in diagnostic histopathology regarding specimens with equivocal cellular morphology.     

Potentially malignant epithelial oral lesions: discrepancies between clinical and histological diagnosis

OBJECTIVE: To evaluate the discrepancy index between the clinical and histological diagnosis and the prevalence of epithelial dysplasia and carcinoma in 45 patients with potentially malignant epithelial oral lesions (PMEL).PATIENTS AND METHODS: We submitted 45 patients with PMEL to clinical examination and obtained a biopsy from each. The results of histological diagnosis were compared to the clinical diagnosis.
RESULTS: Clinical diagnosis showed that the most common PMEL was leukoplakia followed by lichen planus and by actinic cheilitis associated with leukoplakia. The most common site was the buccal mucosa. Histological diagnosis revealed that 46.7% of the PMEL were lichen planus. The discrepancy index between clinical and histological diagnosis was 24.4%. The higher discrepancy index occurred among leukoplakias. The prevalence of epithelial dysplasia and carcinoma was 17.8%.
CONCLUSIONS: We conclude that all PMEL should be submitted to a microscopic analysis because the discrepancy between clinical and histological diagnosis was present in a quarter of these lesionS. Otherwise, the epithelial dysplasia and carcinoma were more frequent in the leukoplakias.     

Detection of potentially malignant and malignant lesions of oral cavity using autofluorescence visualization device

Light-based oral cancer screening aids have been developed in identifying potentially malignant and malignant lesions of oral cavity at their earliest stage. The VELscope system is a simple hand-held device that facilitates the direct visualization of oral-cavity fluorescence for the detection of precancerous and cancerous lesions. Some published reports have shown that this system can assist in the detection of precancerous and cancerous lesions, but there is no evidence that it can distinguish between them. We studied whether objective discrimination criteria can be set for this system when observing oral mucosal lesions. We examined 74 cases with biopsy-confirmed oral mucosal lesions; 37 squamous cell carcinoma lesions, 14 moderate to severe epithelial dysplasia lesions, 13 mild epithelial dysplasia lesions and 10 lichen planus lesions. Lesions were examined macroscopically under the conventional overhead light, and then, examined by this device. Each examination was recorded with a digital camera. We contrasted findings with histopathological manifestation, and calculated the attenuation score. It is found that several conditions and sites, such as keratinization and the degree of inflammatory cell infiltration, were associated with detection sensitivity using this device. Based on the attenuation scores, a significant difference was seen between squamous cell carcinoma and epithelial dysplasia. It is suggested that this device might be a valuable adjunct in the early detection of potentially malignant and malignant lesions of the oral cavity.     

Histochemical analysis of pathological alterations in oral lichen planus and oral lichenoid lesions

Lichen planus is a dermatologic disease of unknown etiology characterized by keratotic plaques on the skin. Many patients also harbor white lesions of the oral mucosa. The literature contains numerous reports of lichen planus-like lesions evolving in conjunction with the administration of a variety of pharmacologic agents. It is difficult, if not impossible, to distinguish such lesions from one another. The present study evaluated the epithelial and basement membrane thickness, mast cells (intact cells and degranulated cells subepithelially) and the presence or absence of blood vessels in oral lichen planus and oral lichenoid lesions. The evaluation was done using the periodic acid-schiff (PAS) and toluidine blue staining techniques on 20 cases each of oral lichen planus and oral lichenoid lesions and 5 control specimens of normal buccal mucosa. The results showed an increased number of degranulated mast cells in areas of basement membrane degeneration, increased vascularity and increased PAS-positive basement membrane thickness in oral lichen planus as compared with oral lichenoid lesions. Reduced epithelial thickness was found in oral lichen planus. The present study emphasizes the importance of these parameters in differentiating oral lichen planus from oral lichenoid lesions using special staining techniques.     

Malignant potential of oral lichen planus: observations in 722 patients from India

Abstract The malignant potential of oral lichen planus was assessed on the basis of observations in 722 patients found among 27,599 individuals examined in various epidemiologic studies in Kerala, Ernakulam district, India. Seven hundred and two patients with oral lichen planus were re-examined annually over a 10-year period with a mean observation period of 5.1 years. Most of the lesions (93%) were observed among tobacco users. Carcinoma developed in 3 (0.4%) patients with oral lichen planus. Clinically, all 3 had atrophic components in their lesions, and all were tobacco users. The relative risk of a lichen planus developing oral cancer compared to a tobacco user was estimated as 3.3. However, this relative risk was not significant. Histologically, 74% of the 94 biopsies from oral lichen planus showed epithelial atrophy. Two of the 3 in whom cancer developed also showed epithelial atrophy. It is felt that epithelial atrophy probably renders the mucosa more vulnerable to the carcinogenic action of tobacco. Although this study could not confirm the precancerous nature of this disease with a high degree of certainty, the disease did not appear to be innocuous either.     

Malignant potential of oral lichen planus: observations in 722 patients from India

The malignant potential of oral lichen planus was assessed on the basis of observations in 722 patients found among 27,599 individuals examined in various epidemiologic studies in Kerala, Ernakulam district, India. Seven hundred and two patients with oral lichen planus were re-examined annually over a 10-year period with a mean observation period of 5.1 years. Most of the lesions (93%) were observed among tobacco users. Carcinoma developed in 3 (0.4%) patients with oral lichen planus. Clinically, all 3 had atrophic components in their lesions, and all were tobacco users. The relative risk of a lichen planus developing oral cancer compared to a tobacco user was estimated as 3.3. However, this relative risk was not significant. Histologically, 74% of the 94 biopsies from oral lichen planus showed epithelial atrophy. Two of the 3 in whom cancer developed also showed epithelial atrophy. It is felt that epithelial atrophy probably renders the mucosa more vulnerable to the carcinogenic action of tobacco. Although this study could not confirm the precancerous nature of this disease with a high degree of certainty, the disease did not appear to be innocuous either.     

Comparison of cytokeratin, filaggrin and involucrin profiles in oral leukoplakias and squamous carcinomas

As the distribution pattern of cytokeratin (CK), filaggrin and involucrin has recently been suggested to discriminate between benign and malignant epithelial growths, biopsies of healthy oral mucosa, leukoplakias without and with dysplasia and squamous cell carcinomas were examined immunohistochemically using a panel of 4 monoclonal antibodies (AB) against different cytokeratin polypeptides (34 beta E12, KL1 and Pkk1) and filaggrin as well as a polyclonal AB to involucrin. Major and statistically significant differences were observed in the profiles of CKs (except Pkk1), filaggrin and involucrin between leukoplakias without and with epithelial dysplasia. However, the alteration in the expression of CKs, filaggrin and involucrin proved to be not a constant feature in leukoplakias with dysplasia as a considerable portion (20-25%) of them revealed the profiles of CKs, filaggrin and involucrin similar to those of benign leukoplakias, and vice versa. Immunostaining of these antigens did not define the diagnosis of dysplasia in leukoplakias more precisely than grading in conventional histology can do so far. However, immunohistochemical sensitivity in detecting a broad range of variation in the abnormal maturation patterns of keratinocytes in leukoplakias with dysplasia can be used to divide these lesions into subgroups to elucidate their prognosis in follow-up studies.     

CO2 laser surgery of oral premalignant lesions

Experiences gained in the CO2 laser treatment of patients with oral dysplastic precancerous lesions are presented. Besides 7 lichens planus, 50 leukoplakias of all grades of dysplasia, and carcinoma in situ and one lentigo maligna were removed superficially with a defocused laser. Within the average follow-up period of 37 months, 22% local recurrences were observed. In comparison with conservative drug therapy, conventional surgical procedures, and cryosurgical therapy, the CO2 laser treatment of multicentric premalignant diseases of the oral mucosa can be recommended as an alternative therapy.     

In situ DNA hybridization analysis of oral papillomas, leukoplakias, and carcinomas for human papillomavirus.

Twenty-one papillomas, 23 ordinary benign keratoses, 13 smokeless tobacco keratoses, 10 verrucous hyperplasias, 10 verrucous carcinomas, 17 squamous cell carcinomas, 3 epithelial dysplasias, and 6 lichen planus lesions were evaluated for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/35, with biotinylated double-stranded DNA probes by in situ hybridization. Sixty-two percent (13/21) of oral squamous papillomas were positive for HPV DNA. HPV DNA types 6 and 11 demonstrated the strongest reactivity. Of the 13 cases, 10 also showed some reactivity with HPV-16/18 and -31/33/35. None of the cases of keratoses, epithelial dysplasia, squamous cell carcinoma, verrucous hyperplasia, verrucous carcinoma, or lichen planus were positive for HPV DNA. This study confirms the consistent and frequent finding of HPV DNA in oral squamous cell papillomas and the inconsistency of being able to identify HPV DNA in keratotic, premalignant, or cancerous lesions of the oral mucous membranes.     

Clinical significance and usefulness of quantification of telomerase activity in oral malignant and nonmalignant lesions

We quantified telomerase activity (TA) in patients with oral and maxillofacial malignant and nonmalignant lesions, and compared it with their clinical status and grade of malignancy. Fifty-two malignant and 52 nonmalignant lesions were analyzed. All malignant lesions were pathologically diagnosed as oral squamous cell carcinoma (OSCC). Normal gingival tissue served as a control. These specimens were obtained by biopsy or surgical resection, and stored at -80 degrees C until use. TA was quantified by a fluorescence-based TRAP method. TA levels ranged from 0.00 to 95.24 (average 33.24)U/microgP in 52 malignant lesions, and from 0.00 to 79.35 (average 11.91)U/microgP in 52 nonmalignant lesions (P < 0.0001). TA was detected in 96.2% of malignant and 65.4% of nonmalignant lesions. There was no relationship between TA levels and clinical stages or YK classification. However, under WHO classification, there were significant differences (P < 0.05) between Grades I and III or II + III. Among nonmalignant lesions, epithelial dysplasia showed a significantly higher TA level than that of oral lichen planus (P < 0.05) and other benign lesions (P < 0.0001). Oral lichen planus also significantly differed from other benign lesions (P < 0.05). These results suggest that TA is related to the histological grade of malignancy, and is also useful as a prognostic predictor for precancerous lesions and conditions.     

Smoking habits of 611 patients with oral lichen planus.

The smoking habits of 611 patients (68 per cent females and 32 per cent males) with oral lichen planus were studied. Forty-six per cent were daily smokers, 4 per cent smoked only at social events, and 50 per cent were nonsmokers. In comparison with the nonsmokers, the daily smokers showed significantly lower prevalences of reticular and atrophic types of oral lichen planus lesions and a significantly higher prevelance of the plaque type (P less than 0.001). It is suggested that these findings depend on a mechanism whereby original atrophic and reticular types of lesions are altered into the plaque type of lesions under the influence of smoking. The question arises whether such plaque type of lesion can be regarded as leukoplakias which have been superimposed on the oral mucosa affected by lichen planus.     

Distribution of ABO blood group substances in various types of oral lichen planus

Formalin-fixed, paraffin-embedded tissue sections of fifty oral lichen planus lesions including hypertrophic, atrophic and erosive types, were examined by an immunofluorescent technique for the presence of the ABO blood group antigens. The antigen activity in lichen planus lesions was compared with the reactivity of normal human and Rhesus monkey oral mucosa as controls, and the reactivity of adjacent normal epithelium in the same specimen. A difference in the distribution of the blood group substances was observed in the three different types of oral lichen planus. The hypertrophic showed the strongest staining reaction approaching that of the normal, whereas a decrease in quantity of blood group substances was seen in the atrophic, and a tendency to complete loss in the erosive type. There was a marked tendency for loss of staining to be greater in lesions from older patients; this could be related to the greater frequency of atrophic and erosive lesions in the elderly.     

DJ-1和PTEN在口腔鳞癌及癌前病变中的检测及意义

目的检测口腔鳞癌及癌前病变中DJ-1和PTEN的表达并分析其临床意义。方法免疫组织化学方法检测46例口腔鳞癌,16例口腔扁平苔藓,19例白斑和10例正常口腔黏膜标本中DJ-1、PTEN两种蛋白的分布,分析各个指标和病理参数的关系。结果口腔鳞癌组织中DJ-1增高,阳性率为89%（41/46）,与正常口腔黏膜、口腔白斑和口腔扁平苔藓相比,差异有统计学意义（P=0.000）;PTEN在口腔鳞癌组织中降低,阳性率为57%（26/46）,与正常口腔黏膜、白斑和口腔扁平苔藓对比,差异有统计学意义（P=0.000）。经Spearman等级相关检验,DJ-1和PTEN之间的相关系数r为-0.67,P〈0.01,差异具有统计学意义,表明DJ-1和PTEN之间存在负相关。结论 DJ-1、PTEN在口腔鳞癌发生过程中均起着一定的作用;DJ-1可能通过负性调控PTEN而导致口腔肿瘤的发生。     

Distribution of ABO blood group substances in various types of oral lichen planus

Formalin-fixed, paraffin-embedded tissue sections of fifty oral lichen planus lesions including hypertrophic, atrophic and erosive types, were examined by an immunofluorescent technique for the presence of the ABO blood group antigens. The antigen activity in lichen planus lesions was compared with the reactivity of normal human and Rhesus monkey oral mucosa as controls, and the reactivity of adjacent normal epithelium in the same specimen. A difference in the distribution of the blood group substances was observed in the three different types of oral lichen planus. The hypertrophic showed the strongest staining reaction approaching that of the normal, whereas a decrease in quantity of blood group substances was seen in the atrophic, and a tendency to complete loss in the erosive type. There was a marked tendency for loss of staining to be greater in lesions from older patients; this could be related to the greater frequency of atrophic and erosive lesions in the elderly.     

细胞角蛋白CK19在口腔粘膜癌变过程中的变化

目的：探讨口腔粘膜癌变过程中CK19的变化。方法：收集正常口腔粘膜、上皮单纯增生、上皮异常增生和口腔鳞癌活检标本共53例，用免疫组化、电泳和Western杂交方法研究上皮中CK19的表达。结果：CK19表达于有上皮异常增生的复层鳞状上层和口腔鳞癌尤其是低分化鳞癌的癌细胞中。随病变程度加重，CK19表达的阳性率，表达强度和占细胞角蛋白构成比显著增加。结论：CK19表达于粘膜上皮的基底上层可作为口腔癌前病变的辅助标志，CK19表达增加是 口腔粘膜病变过程中的早期事件。     

Expression of Class II transplantation antigens by epithelial cells in oral candidosis, oral lichen planus and gingivitis

Biopsies from normal oral mucosa and oral mucosa affected by candidosis, lichen planus or gingivitis were compared with respect to the expression of two Class II transplantation antigens, HLA-DR and HLA-DQ, by epithelial cells and the relationship of these antigens to the distribution and frequency of T-lymphocytes. Indirect immunohistochemistry with different mouse monoclonal antibodies was used on frozen and acetone-fixed sections. To evaluate the results, a score system based upon the expression of the Class II transplantation antigens by epithelial cells and the frequency of T-lymphocytes was used. In oral candidosis there was a marked expression of HLA-DR antigens throughout the epithelium. In addition, this type of epithelium was the only one that expressed HLA-DQ antigens. An intense intraepithelial infiltration of T-lymphocytes was observed. Oral lichen planus and gingivitis did, to a much lesser extent, cause the expression HLA-DR antigens by the epithelial cells. In both lesions, the number of T-lymphocytes within the epithelium did not exceed the number found in epithelium of normal mucosa. In these types of lesions, the subepithelial infiltrate varied in intensity but was mainly composed of T-lymphocytes reactive with anti-Leu 3a antibodies. The results of the present study imply that epithelial expression of the two different Class II antigens are related to the frequency of the T-lymphocytes and to the proximity of these cells to the epithelial cells.     

Expression of Class II transplantation antigens by epithelial cells in oral candidosis, oral lichen planus and gingivitis

Biopsies from normal oral mucosa and oral mucosa affected by candidosis, lichen planus or gingivitis were compared with respect to the expression of two Class II transplantation antigens, HLA-DR and HLA-DQ, by epithelial cells and the relationship of these antigens to the distribution and frequency of T-lymphocytes. Indirect immunohistochemistry with different mouse monoclonal antibodies was used on frozen and acetone-fixed sections. To evaluate the results, a score system based upon the expression of the Class II transplantation antigens by epithelial cells and the frequency of T-lymphocytes was used. In oral candidosis there was a marked expression of HLA-DR antigens throughout the epithelium. In addition, this type of epithelium was the only one that expressed HLA-DQ antigens. An intense intraepithelial infiltration of T-lymphocytes was observed. Oral lichen planus and gingivitis did, to a much lesser extent, cause the expression HLA-DR antigens by the epithelial cells. In both lesions, the number of T-lymphocytes within the epithelium did not exceed the number found in epithelium of normal mucosa. In these types of lesions, the subepithelial infiltrate varied in intensity but was mainly composed of T-lymphocytes reactive with anti-Leu 3a antibodies. The results of the present study imply that epithelial expression of the two different Class II antigens arc related to the frequency of the T-lymphocytes and to the proximity of these cells to the epithelial cells.     

Assessment of Langerhans' cells in oral lichen planus using monoclonal antibodies

In order to demonstrate Langerhans' cells in epithelium of oral lichen planus, monoclonal antibodies were used as immunological markers in combination with immunohistochemistry. By the use of anti-Ia antibodies the Langerhans' cells were shown to express an increased number of Ia-like antigens in comparison to the amounts found in healthy oral mucosa. The subepithelial infiltrate of mononuclear cells expressed identical Ia-like antigens on their surfaces. With anti-T6 antibodies as immunological markers, the number of Langerhans' cells was found to be virtually identical in diseased and healthy epithelium. Treatment of oral lichen planus with tretinoin resulted in a decrease of epithelial Ia-like antigens compared with the number found in untreated lesions. However, treatment with tretinoin did not alter the frequency of Langerhans' cell marked with anti-T6 antibodies. The present data demonstrate an increased amount of la-like antigens per number of T6-positive Langerhans' cells in diseased oral mucosa compared to healthy conditions. The increased expression of Ia-like antigens on Langerhans' cells and the contemporary finding of Ia-like antigens on the subepithelial T-cells support the opinion that the pathogenesis of oral lichen planus is mainly a cell-mediated type of immunological reaction.     

用DNA倍体分析评估口腔黏膜疾病严重程度

目的:用DNA倍体分析法判断口腔黏膜病病变的严重程度。方法:用小刷刷取口腔黏膜病变处的上皮细胞,直接涂片制成1-2张玻片,经Feulgen染色,用全自动DNA图像分析仪测定细胞核内DNA含量。部分患者在可疑处活检做组织病理检查,将活检病例分成DNA倍体分析组和阴性组,比较两组病例病变的严重程度。结果:303例口腔黏膜病例中有口腔溃疡237例、口腔扁平苔藓17例、红斑34例、白斑25例。经DNA倍体分析其中267例为阴性,36例为阳性。将经活检组织病理检查97例患者分成DNA倍体分析阳性组和阴性组。在36例DNA倍体分析阳性病例中有11例组织像正常或炎性病变、6例轻度异常增生、9例中度异常增生、6例重度异常增生和4例浸润癌,中度异常增生以上改变19例,其阳性率为52.78%;61例DNA倍体分析阴性病例中发现有52例组织像正常或炎性病变、6例轻度异常增生、3例中度异常增生和1例浸润癌,中度异常增生以上改变3例,其阳性率为4.91%。经方差分析,两组之间有显著性差别(x2=30.98,P<0.005)。结论:测定口腔黏膜病变处细胞DNA含量是一种无创伤且能判别出病变严重程度的方法。     

Content and distribution of glycogen in oral epithelial dysplasia

Forty-four oral lesions with epithelial dysplasia and 25 other benign and malignant lesions of the oral mucosa were examined after staining with hematoxylin-eosin and diastase controlled PAS. The intensity of the PAS-positivity for glycogen, the grade of dysplasia, the type of keratinization and the degree of subepithelial inflammation were recorded. Histologically normal epithelium at the margins of the lesions were used as controls. The presence and amount of glycogen in normal epithelium at the margins of the lesions were used as controls. The presence and amount of glycogen in normal epithelium at the margin of the lesions were used as controls. The presence and amount of glycogen in normal epithelium varied with the form of keratinization in that non- or parakeratinized epithelium was rich in glycogen whereas there was a negative glycogen-reaction in orthokeratinized epithelium. The most striking feature was an abrupt limitation of the glycogen at the junction between nondysplastic and dysplastic epithelium. The difference in the amount of glycogen in normal and dysplastic epithelium as assessed semiquantitatively, was statistically significant. There was no statistically significant difference in glycogen content with different degrees of dysplasia. The diastase controlled PAS-staining may therefore be a useful method of distinguishing dysplastic from nondysplastic epithelium in doubtful cases. Pseudoepitheliomatous hyperplastic epithelium covering granular cell myoblastoma did not contain any glycogen. Five of six squamous cell carcinomas and four verrucous carcinomas contained no demonstrable glycogen. Glycogen was present in the epithelium of the cases of lichen planus and "denture hyperplasia" investigated.