Comparing flow cytometric analysis and nucleolar organizer region enumeration in archival oral premalignant lesions

Flow cytometric analysis (FCA) and silver colloidal nucleolar organizer region-associated protein staining (AgNOR) have been used individually in assessing the histopathologic nature of various human tumors. However, few researchers have investigated the relationship between the two techniques in a single series. In a retrospective study, we examined 36 premalignant lesions of the oral cavity by FCA and AgNOR on formalin-fixed, paraffin-embedded tissue submitted to the University of Tennessee, Memphis, oral pathology laboratory. Three categories of epithelial dysplasia were represented (9 mild. 9 moderate, 6 severe), as well as four epithelial hyperplasias without dysplasia, three squamous cell carcinomas, and five fibrous nodules as controls. Parameters recorded for each case included age. race, gender, site, light microscopic diagnosis (LMD). DNA index (DI), total proliferative index (TPI), S-phase (S), range of nucleolar organizer regions (RNOR), and mean number of nucleolar organizer regions (MNOR). The average maximum nucleolar organizer region count (AMXNOR) for each LMD category was also calculated. The objective of the study was to determine if FCA or AgNOR aided in the subjective LMD of oral premalignant lesions and if the parameters recorded for the specimens exhibited any positive correlation. The FCA results indicated an abnormal DI in 6 of the 24 dysplastic lesions. A positive partial correlation was seen between DI and MNOR (r = 0.434: P<0.012) and TPI and S (r = 0.774; P < 0.0001), holding gender and race constant. Additionally, the AMXNOR exhibited a slight tendency to increase for each increasing grade of dysplasia but this could not be confirmed statistically. The results indicate that there is a positive correlation between FCA and AgNOR but that neither FCA nor AgNOR were a diagnostic aid in grading oral mucosal dysplasia.     

微小RNA与口腔癌前病变

微小RNA是非编码单链小分子RNA,通常在转录后水平通过降解抑制目标信使RNA参与基因调控,目前研究发现微小RNA与口腔癌关系密切,在某些口腔癌前疾病的癌变过程中发挥着重要作用,此文就微小RNA与口腔癌前病变的关系作一综述。     

Possible premalignant character of oral lichen planus the Amsterdam experience

In the present paper the 21-yr experience of the Department of Oral and Maxillofacial Surgery and Oral Pathology, and the Department of Otorhinolaryngology of the Free University Hospital, Amsterdam, is reported with regard to the possible premalignant character of oral lichen planus. The study consists of two parts: 1) the follow-up of 113 patients with histopathologically proven oral lichen planus, and 2) a search for lichen planus in 727 patients who have been admitted for oral cancer. Three patients with histopathologically proven lichen planus developed a squamous cell carcinoma in an average follow-up period of 7 yr. In the 727 patients with oral cancer, two additional patients with the simultaneous occurrence of oral lichen planus were observed. Our experience gives some but not very strong support to the hypothesis that oral lichen planus is a premalignant condition.     

Cytomorphometric analysis of squames obtained from normal oral mucosa and lesions of oral leukoplakia and squamous cell carcinoma

Ramaesh T, Mendis BRRN, Ratnatunga N, Thattil RQ: Cytomorphometric analysis of squames obtained from normal oral mucosa and lesions of oral leukoplakia and squamous cell carcinoma. J Oral Pathol Med 1998; 27: 83–6. © Munksgaard, 1998.
Cell and nuclear diameters (CD and ND) were measured in squames obtained from normal buccal mucosa and lesions of oral leukoplakia and squamous carcinoma (SCC) also from buccal mucosa. The study groups consisted of Group 1: normal buccal mucosa ( n = 40); Group 2: lesions with no epithelial dysplasia ( n = 58); Group 3: lesions with epithelial dysplasia ( n = 27); and Group 4: SCC lesions ( n = 51). The mean CD and ND values were: Group 1: 51.78 (± 0.11) and 8.36 (± 0.49); Group 2: 45.73 (± 0.16) and 8.31(± 0.68); Group 3: 41.32 (± 0.13) and 9.04 (± 0.46); Group 4: 38.58 (± 0.11) and 10.10 (± 0.56) urn, respectively. Correlation between the ND and CD was positive for Group 1 ( r = 0.78, P < 0.05) and Group 2 ( r = 0.33, P < 0.05). There were no significant correlations in Groups 3 and 4. ANOVA showed significant differences ( P < 0.05) for CD between all four groups. Except between Groups 1 and 2, the ND was significantly different ( P < 0.05) between all groups. The results indicate that ND and CD could possibly be sensitive parameters in the diagnosis of oral premalignant and malignant lesions.     

Molecular genetics of premalignant oral lesions

Oral squamous cell carcinoma (OSCC) is characterized by cellular and subcellular alterations that are associated with a progression towards dedifferentiation and growth. There are several histologically distinct lesions of the oral cavity which have malignant potential. These are leukoplakia, erythroplakia, lichen planus, and submucous fibrosis. These are characterized by a spectrum of chromosomal, genetic, and molecular alterations that they share with each other as well as with the malignant lesions that develop from them. In this review we summarize the investigation of the molecular genetics of each of these lesions and relate them to the alterations, which have been demonstrated in OSCC, to define their location on the continuum of changes, which lead to malignant transformation.     

Aberrant glycosylation in oral malignant and premalignant lesions

Cell surface carbohydrates serve as differentiation and developmental markers characteristic of different cell and tissue types. The expression of these carbohydrate antigens is often significantly altered in tumors, particularly in those arising from epithelial tissues. Analysis of cell surface carbohydrates in oral epithelium have shown that in normal epithelium they are expressed in a way that shorter carbohydrates are found on basal cells and that these carbohydrate structures are elongated parallel to terminal differentiation. The carbohydrate expression is altered in oral carcinomas and in some oral premalignant lesions. The change in carbohydrate expression can at present be explained by the lack of synthesis of specific glycosyltransferases. We have found mosaicism in the expression of carbohydrate antigens in all tumors and have found that the expression of a specific carbohydrate in the deep invasive parts of the tumor correlates with tumor prognosis.     

Low prevalence of oral mucosal lesions in HIV-1 seropositive African women

In Nairobi (Kenya) 334 women prostitutes of whom 80.5% were HIV-1 positive, were examined for oral mucosal lesions; 15.6% of seropositive, and 4.6% of seronegative, women had oral mucosal lesions, predominantly oral candidiasis. In the seropositives, 8.6% had erythematous, 1.1% had hyperplastic candidiasis, and 0.4% had hairly leukoplakia as the only oral lesions; 0.4% had a combination of erythematous and hyperplastic candidiasis, and 1.5% had combinations of pseudomembranous and erythematous candidiasis in the presence of hairly leukoplakia. Of the 211 seropositive women for whom we knew the first date on which a positive serologic test was obtained, the likelihood of developing an oral mucosal lesion was found to be dependent on the duration of seropositivity. The low incidence of oral mucosal lesions in this population may be due to the relatively recent acquisition of HIV-1 infection.     

Expression of p16 and CDK4 in oral premalignant lesions and oral squamous cell carcinomas: a semi-quantitative immunohistochemical study

The protein, p16, the product of cyclin-dependent kinase number 2 (CDKN2) gene, is one of the negative regulators of the cell cycle. CDK4, encoded by CDK4 gene, is the substrate of p16. We investigated the expression of p16 and CDK4 and their role in the progression of oral premalignant lesions (OPLs) and oral squamous cell carcinomas (OSCCs) in a Chinese cohort. A total of 74 samples were obtained from patients with hyperkeratosis (10), OPLs [30; mild (10), moderate (10) and severe (10) dysplastic lesions], OSCCs (15; 8 non-metastatic, 7 metastatic), and normal oral tissues (10), together with local lymph nodes (9) of patients with metastatic OSCCs. A labelled streptavidin biotin (LSAB) immunohistochemistry assay was performed and a semi-quantitative method was used to evaluate the staining intensity. The staining patterns of p16 and CDK4 were similar in all tissues and were located in both the nuclei and the cytoplasm. However, the antigen distribution characteristics and the degree of expression of both p16 and CDK4 varied at different developmental stages of the lesions. Hyperkeratotic and dysplastic lesions tended to display a progressively increasing degree of p16- and CDK4-positive nuclei as compared with normal tissues. Also, positive staining cytoplasm was highly evident in OSCCs with a very low nuclear staining (P<0.05). Forty-six of 56-, p16-positive cases were CDK4-positive, while only 6 were CDK4-positive but p16-negative, implying a high correlation between these parameters (r=0.813, P<0.001). This study indicates that the expression of p16 and CDK4 is intimately involved in the development of OPLs and OSCCs and the likely existence of a positive feedback loop between p16 and CDK4.     

The efficacy of oral lumenoscopy™ (ViziLite®) in visualizing oral mucosal lesions

Early diagnosis of oral mucosal lesions has been advocated as a means of improving outcomes of cancer therapy. Improved visualization of mucosal lesion* may aid in diagnosis by guiding tinue sampling or referral. This multi‐center study reports the effect of chemiluminescent light (ViziLite) upon visualization of mucosal lesions. The cftemiluminescent light did not appear to improve visualization of red lesions, but white lesions and lesions that were both red and white showed enhanced brightness and sharpness.     

Self-awareness of premalignant oral lesions among veterans attending six U.S. Veterans Affairs Medical Centers

Early identification is key to reducing the morbidity and mortality of oropharyngeal cancer. This study identified factors associated with self-awareness among patients newly diagnosed with a premalignant oral lesion. Data describing sociodemographics, medical/dental histories, tobacco/alcohol use and oral health were obtained by questionnaire and clinical examination of 73 veterans at six U.S. Veterans Affairs Medical Centers. Lesion types included homogenous and non-homogenous leukoplakia, smokeless tobacco lesion (STL), papilloma, lichen planus and erythroplakia. Prior to diagnosis, 29 subjects (39.7%) were unaware of their lesion. In bivariate analyses, lesion self-awareness was associated with anatomic location, multifocal/generalized appearance, pain, oral sores, and cigar use (p<0.05). Awareness varied with lesion diagnosis and was more likely with STL and less likely with homogenous leukoplakia (p<0.05). In multivariate analyses, awareness was predicted by the presence of a lesion on easily visible mucosa (adjusted odds ratio, OR=11.2) and a history of mouth sores (OR=11.2). These findings identified marked variations in patient self-awareness of oral premalignant conditions.     

甲苯胺蓝活体染色发现早期口腔粘膜癌变的评价

目的：为早期发现口腔粘膜斑纹类疾病的中的可癌变者,试用Ｏratest剂试,并对其敏感性和准确率进行评价,方法：采用英国ＺＩＬＡ公提供的Ｏratest试剂盒,对１９例口腔粘厂主 纹类疾病作常规染色,切取梁色后可疑病损区作组织病理检查,将病量珍断结果与染色结果对照比较,研究其相关性。结果：１９例中病理诊断有上皮异常增生８例,其中梁色阳性６例,阴性２例;无上皮异常增生７,其梁色阳性２例,阴性５例,原位癌４例,其染色阳性３例,阳性１例,观察发现上皮异常增生或原位癌中染色阳性者,其临床表现都有高度增残性角化现象,而无上皮异常增生的染色阳性者,其临床表现有糜料或溃疡,结论：Ｏratest不仅可以有效地提高粘膜癌变,而且对异产生的上皮细胞也有较高的亲和力,由于上皮异常增生是口腔粘膜由正常跨入癌变的第一步,因而对Ｏratest染色阳性者应引起高度警惕,其敏感性可达７５％,准确率达７４％,Ｏratest作一种筛选剂对于早期发现口腔粘膜的癌变或癌前病变切有临床意义。     

口腔黏膜癌前病变和口腔鳞癌组织Fas/FasL的表达及其意义

目的：研究调亡相关基因Fas／FasL在正常口腔黏膜、上皮异常增生和口腔鳞癌组织中的表达及意义。方法：应用免疫组织化学方法检测10例正常口腔黏膜、26例上皮异常增生、38例口腔鳞癌组织及肿瘤浸润淋巴细胞（TIL）中Fas／FasL的表达。结果：Fas在正常口腔黏膜中广泛表达;上皮异常增生和鳞癌组织表达明显下调（P〈0．05）;Fas表达与口腔鳞癌分化程度有关;FasL在正常口腔黏膜不表达;上皮异常增生和鳞癌组织表达明显上调（P〈0．05）;FasL表达与口腔鳞癌分化程度无关（P〉0．05）;TIL细胞Fas、FasL阳性表达率为81．6％和84．2％。结论：Fas表达与口腔黏膜上皮细胞的自然分化成熟、衰老及口腔鳞癌的形成和肿瘤的恶性度有关;FasL的表达上调可能是口腔鳞癌组织免疫反攻击的体现;Fas、FasL可作为监测口腔上皮癌变的标记物。     

Occurrence of oral mucosal lesions, the influence of tobacco habits and an estimate of treatment time in an adult Swedish population

A randomly selected sample of adult subjects living in a Swedish county was examined for the presence of oral mucosal lesions. Nine hundred twenty (920, 95%) of the selected sample of 967 subjects, comprising approximately 0.75% of the total adult population, were examined; lesions were registered in 596 of the 920. The registered prevalence levels were very similar to earlier reported data from Sweden. Further, the relationship between tobacco habits and mucosal lesions was analyzed and the time needed for treatment of the lesions was estimated. A positive correlation could be demonstrated between tobacco use and leukoplakia, frictional white lesion, coated tongue, hairy tongue and excessive melanin pigmentation, while a negative correlation was observed for geographic tongue and aphthous ulcers. Approximately 70% of the lesions were associated with local irritants (e.g. dentures, tobacco, cheek and lip biting etc.). The estimated mean time required for registration and management of oral mucosal lesions in the studied group of adults was 24 min per individual.     

Expression of p16 in oral cancer and premalignant lesions

Background:  Expression of p16 has been proposed as a marker for malignant transformation. This study aimed to evaluate p16 expression in oral squamous cell carcinoma (OSCC) and premalignant lesions including oral leukoplakia (OL) with and without dysplasia.
Methods:  Expression of p16 was investigated in 56 samples including OSCC, OL with and without dysplasia, and normal oral mucosa. Expression of p16 was identified by immunohistochemistry, using the CINtecTM p16INK4a Histology Kit. Both nuclear and/or cytoplasmic staining of the keratinocytes were considered to be positive and the percentage of positive cells was calculated.
Results:  Expression of p16 was detected in 3/16 (18.75%) cases of OSCC, in 4/15 (26.7%) cases of OL without dysplasia, and in none of OL with dysplasia and normal mucosa. No significant differences in p16 expression prevalence were found among OSCC, OL with and without dysplasia and normal mucosa. The percentages of positive cells in OSCC and OL without dysplasia were 0.89 and 0.17, respectively. No significant difference in the percentage of positive keratinocytes was found.
Conclusion:  As a marker, p16 is not reliable for oral mucosal dysplasia and malignant transformation.     

A preliminary report on prevalences of oral mucosal lesions in a Swedish population

ABSTRACT A study has been conducted to assess the prevalence of oral soft tissue lesions. In cooperation with the public health screening organization of the County of Uppsala in Sweden, all inhabitants older than 14 years of age in two communities, Håbo and Enköping, will be called for examination. So far, 8,696 individuals have been examined. Preliminary prevalence figures on 33 lesions are reported.     

Central papillary atrophy of the tongue among bidi smokers in India: a 10–year study of 182 lesions

The occurrence of central papillary atrophy of the tongue among tobacco users, its clinical characteristics and the long term behavior in relation to changes in tobacco use was studied in 182 individuals in Ernakulam district, Kerala, India. Almost all (98%) lesions occurred among bidi smokers. Clinically, about 31% occurred in combination with bidi smoking associated lesions such as palatal erythema (14%), leukoplakia (8%) or both (3%). Histologic evaluation in 12 biopsies using single PAS stained sections showed candidal hyphae in 67%. A 10-yr follow-up (mean: 6.7 yr) of the 182 lesions showed that the regression was highest (87%) among those who stopped their smoking habit and persistence among those who did not reduce or stop their smoking habits. The findings from this study confirm a strong link between bidi smoking and central papillary atrophy of the tongue in rural Indian populations.     

Progressive and regressive changes in Hungarian oral leukoplakias in the course of longitudinal studies

ABSTRACT Follow-up studies of 520 patients with leukoplakia during a 25-year period showed changes in the clinical type in 66 cases, i.e. 12.7 %. Regressive changes occurred in 9 %, progressive changes in 3.7 %. The highest frequency of change in the clinical type was found in the group of erosive leukoplakias. The most frequent changing sites were the labial mucosa, commissures and buccal mucosa. Of the etiologic factors, smoking and Candida infection seemed to be correlated with the change of type. Oral leukoplakia should be considered a dynamic changing lesion of the oral mucosa.     

The prevalence of oral mucosal lesions in a population in Ljubljana, Slovenia

The purpose of the present study was to evaluate the prevalence of oral mucosal lesions and conditions in a population in Ljubljana, capital of Slovenia. A total 1609 subjects represented the study population in the survey about the periodontal treatment needs in a population in Ljubljana, conducted from 1983 to 1987. Ten years later the same 1609 subjects were invited to the second examination. Altogether, 555 (34.5%) of the invited subjects in the age range 25-75 years came for an interview and clinical examination at the Department of Oral Medicine and Periodontology of the Dental Clinic in Ljubljana. Oral mucosal lesions and conditions were evaluated according to the WHO Guide to Epidemiology and Diagnosis of Oral Mucosal Diseases and Conditions. The results showed the presence of one or more mucosal lesions in 61.6% of the population. Fordyce's condition was observed the most frequently (49.7%) followed by: fissured tongue (21.1%), varices (16.2%), history of herpes labialis (16.0%), history of recurrent aphthae (9.7%), denture stomatitis (4.3%), leukoplakia (3.1%), cheek biting (2.7%), lichen planus (2.3%), frictional keratosis (2.2%), geographic tongue (2.2%), geographic and fissured tongue together (1.1%), mucocele (0.9%), smoker's palate (0.5%) and angular chelitis (0.4%). In the population examined, no oral malignancies were observed. Mucosal lesions like whitish lesions, denture related lesions, fissured tongue, varices and mucocele were more prevalent with increasing age. Tobacco-related lesions (leukoplakia and smoker's palate together) were significantly more prevalent among men than among women (P<0.05), while lichen planus, denture stomatitis and herpes labialis occurred more frequently in the female population.     

Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions

BACKGROUND: The histologic classification of pre-cancerous and cancerous oral lesions has generally shown poor agreement between pathologists, but lesion and patient characteristics that may affect diagnostic reliability have not been explored. METHODS: Eighty-seven clinically suspicious oral lesions biopsied from 81 patients with previous upper aerodigestive tract cancer were independently classified by their local pathologist and a central pathology committee. Interobserver reliability between the local pathologist and the central pathology committee was measured with weighted kappa (kappa w) statistics and corresponding 95% confidence intervals (CI). RESULT: The kappa w for pathologic diagnosis was 0.59 (95% CI: 0.45, 0.72), and was higher for lesions without inflammation (0.67 (95% CI: 0.53, 0.80) than inflamed lesions (-0.10 (95% CI: -0.27, 0.07)). Greatest agreement was seen for lesions located in the buccal mucosa/vestibule (kappa w = 0.68 (95% CI: 0.46, 0.91)) and tongue (kappa w = 0.62 (95% CI: 0.40, 0.84)). Least agreement was found for lip/labial mucosa lesions (kappa w = -0.04 (95% CI: -0.34, 0.27)). Punch biopsies (kappa w = 0.67 (95% CI: 0.54, 0.80)) had greater interobserver reliability than wedge biopsies (kappa w = 0.38 (95% CI: 0.12, 0.64)). CONCLUSIONS: These data suggest that the presence of inflammation, lesion site, and biopsy technique modifies the reliability of oral lesion histologic diagnoses.