Prognostic implication of silver-binding nucleolar organizer regions (AgNORs) in oral squamous cell carcinoma

Silver-binding nucleolar organizer regions (AgNORs) were counted in sections from formalin-fixed, paraffin-embedded tissue blocks of oral squamous cell carcinoma. Thirty-nine cases, that comprised poor prognostic group (n = 19) and good prognostic group (n = 20), were examined with respect to the relation between AgNOR counts and histologic grading, and correlation between AgNOR counts and prognosis. The pooled mean AgNOR counts were: Grade 1 carcinomas, 6.39 +/- 1.67 (mean +/- SD; n = 35); Grade 2, 9.74 +/- 1.72 (n = 3). Mean AgNOR count of Grade 3 was 6.19 +/- 2.37 (n = 1). The pooled mean AgNOR count in poor prognostic group was higher than that in good prognostic group. Five-year survival rate of the cases with high AgNOR counts (greater than or equal to 6.5) was significantly lower than that with low AgNOR counts (less than 6.5). High AgNOR counts are highly suggestive of poor prognosis in oral squamous cell carcinoma.     

Evaluation of argyrophilic nucleolar organizer regions (AgNORs) in oral carcinomas in relation to human papillomavirus infection and cytokinetics

The numbers of argyrophilic nucleolar organizer regions (AgNORs) were quantified in oral carcinomas ( n = 39) with or without human papillomavirus (HPV) infection. The AgNOR counts of the HPV-positive samples (7.15±2.13) were not significantly ( P = 0.09) higher than those of the HPV-negative ones (6.16±1.89). Furthermore, the lesions infected with multiple HPV types had greater counts than those with HPV type 16/18 infection alone. Significant differences were observed between the mean counts of the poorly (10.50±0.54), moderately (7.31±1.07) and well- (5.12±0.85) differentiated carcinomas. The mean AgNOR numbers in the oral carcinomas at TNM stages III/IV were found to be significantly ( P < 0.01) higher than the numbers in corresponding stage II lesions. Cytokinetics of the lesions assessed by the bromodeoxyuridine (Brdu) labelling index (LI%) showed a linear correlation (r=0.91: P < 0.0001) with their respective mean AgNOR counts.     

Differential lectin-bindings in normal and precancerous epithelium and squamous cell carcinoma of the oral mucosa

In order to establish a useful and objective marker of malignancy of oral mucosa, the binding sites for Ulex europaeus agglutinin I (UEA-I). Bandeiraea simplicifolia agglutinin I (BSA-I) and peanut agglutinin (PNA) were comparatively examined in the surgical materials from the normal, dysplastic and cancerous epithelium of the oral mucosa by a novel lectin-antilectin immunoperoxidase method. Based on the staining patterns of the normal keratinized epithelium, UEA-I was regarded as the marker for the prickle cells, BSA-I for the cells in the upper prickle to the horny layers, and PNA for those in the basal layer. As the degree of dysplasia advanced, all layers of epithelium came to react with UEA-I and PNA, whereas the BSA-I binding was negative. Positive reactions for UEA-I and PNA were seen in most carcinoma cells other than the keratinizing foci stained by BSA-I. The results indicate that a UEA-I-positive reaction in the basal cells, a PNA-positive in the prickle cells and loss of receptor for BSA-I occur in the course of malignant transformation of oral mucosa, and that these lectins may be regarded as useful markers of oral epithelial cytoplasmic differentiation.     

Histologic grading and nucleolar organizer regions in oral squamous cell carcinomas

Objective

The purposes of this study were to histologically assess different types of oral squamous cell carcinoma and the silver-binding nucleolar organizer region (AgNOR) morphology in neoplastic cells, as well as to quantify the number of AgNORs in each type of carcinoma in order to relate AgNOR count and histologic grading.

Material and Methods

Twenty-eight cases of oral squamous cell carcinoma were divided into 4 groups, namely well-differentiated, moderately differentiated, poorly differentiated, and undifferentiated. For NOR study, 3-µm-thick sections were stained with 50% aqueous silver nitrate solution. The predominant microscopic pattern of NORs was determined. Quantitative analyses of NORs were obtained of all cells present on each histological field using a 0.025 mm² eyepiece graticule. Different histological fields were analyzed until the total number of NORs was 120 cells for each tumor. Kruskall-Wallis test was applied to compare the groups of sample data at a significance level of p=0.05.

Results

The mean number of AgNORs per nucleus was 3.20 for the well-differentiated group, 5.33 for the moderately differentiated one, 8.27 for the poorly differentiated one, and 10.08 for the undifferentiated one. AgNOR count was significantly different (p<0.05) among all of the studied groups.

Conclusion

AgNOR staining technique seems to be a useful diagnostic tool since differences in AgNOR numeric values can be identified in the different types of oral squamous cell carcinoma. This technique is easy to handle and inexpensive, thus justifying its large use in histopathology.     

正常口腔黏膜和口腔鳞癌中人乳头瘤病毒感染率的研究进展

黏膜高危型HPV-16、HPV-18感染是宫颈癌的主要致病因素,且与口腔鳞癌的发生密切相关,但目前对口腔鳞癌中HPV的感染率和亚型的分布尚不十分清楚。作者系统查阅了目前已经发表的有关HPV在正常口腔黏膜或口腔鳞癌中感染率和亚型分布的文献资料,对正常口腔黏膜、口腔鳞癌中人乳头瘤病毒的感染率的研究进展进行了综述。     

口胶粘膜癌前病变及鳞癌角蛋白表达的免疫组化研究

目的研究口腔粘膜标本中角蛋白的表达与分布。方法利用多克隆抗角蛋白抗体A(575)，采用免疫组化技术。结果从正常口腔粘膜，轻、中、重度异常增生到鳞癌角蛋白表达显著增强。A(575)在所有鳞癌标本中均为阳性，但染色强度深浅不一，且随鳞癌分化程度降低而降低，染色弱的病例其临床分期高，更易发生淋巴结转移。结论角蛋白表达的增强在强化上皮细胞中的致癌基因上起作用，这种强化的积累将加速癌前疾病的进展，因此，A575染色可能为预后提供参考依据。     

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.     

Giant cell lesions of the jaws: evaluation of nucleolar organizer regions in lesions of varying behavior

To examine whether giant cell lesions of the jaws (GCL) of varying behavior could be separated histologically, a number of GCL were studied using the AgNOR staining technique for nucleolar organizer regions. The mean AgNOR count of mononuclear cells from recurrent lesions (1.73 ± 0.15) was slightly higher than that of the aggressive lesions (1.54 ± 0.21) and much higher than that of the non-aggressive/non-recurrent lesions (1.33 ± 0.14). Similarly, the mean AgNOR count of the multinucleate giant cells of the recurrent lesions (1.52 ± 0.14) was slightly higher than that of aggressive lesions (1.34 ± 0.092) and much higher than that of non-aggressive/non-recurrent lesions (1.26 ± 0.05). Statistical analysis showed a significant difference between the mean number of AgNORS of recurrent lesions and non-recurrent/non-aggressive ones in both the mononuclear and multinuclear population (p<0.05).     

Shifts in cellular localization of moesin in normal oral epithelium, oral epithelial dysplasia, verrucous carcinoma and oral squamous cell carcinoma

BACKGROUND: Moesin, a member of ERM (ezrin/radixin/moesin) family, links actin filaments of cell surface structure to the cell membrane. The purpose of the study is to assess the shifts in cellular distribution of moesin in normal oral epithelium, oral epithelial dysplasia (OED), verrucous carcinoma (VC), and oral squamous cell carcinoma (OSCC). METHODS: The expression of moesin was evaluated immunohistochemically in paraffin-embedded tissues of 59 specimens of OSCC, 35 specimens of OED, 17 specimens of VC, and five specimens of normal oral epithelium. RESULTS: In the normal oral epithelia, all specimens showed a pattern of membranous expression against the anti-moesin antibody in the basal layer cells. In the OED specimens, moesin was dominantly expressed in the cell membrane except for the cornified layer. In VC and OSCC specimens, almost the whole of the carcinoma cells were stained with anti-moesin antibody. However, in OSCC samples, moesin was markedly expressed increasingly in the cytoplasm and decreasingly in the cell membrane, as compared with OED and VC. In addition, there was a significant correlation between the pattern of moesin expression and tumor differentiation in OSCC. CONCLUSIONS: Our results suggest that it is useful to detect the moesin expression as adjunct to screening mucosal lesions in the oral cavity.     

Antioxidant enzyme levels in oral squamous cell carcinoma and normal human oral epithelium

BACKGROUND: The antioxidant enzymes (manganese- and copper-zinc-containing superoxide dismutases, catalase and glutathione peroxidase) limit cell injury induced by reactive oxygen species. The purpose of the study was to determine whether human oral squamous cell carcinomas have altered antioxidant enzyme levels. This study is the first to undertake this task in human oral mucosa and squamous cell carcinoma. METHODS: Semiquantitative immunohistochemistry was used to examine 26 archived oral squamous cell carcinoma biopsies. Fourteen well-differentiated and 12 poorly differentiated tumors were examined, as were 12 specimens of oral mucosa. All sections were reviewed by two oral and maxillofacial pathologists, and image analysis of the immunostained sections was performed using NIH Image. Antioxidant enzyme staining intensities were compared in the different groups by Duncan's multiple range test. RESULTS: In general, mucosal basal cells displayed lower antioxidant enzyme levels than spinous cells, and primary tumor cells displayed lower antioxidant enzyme staining intensities than did their normal cell counterparts. Moreover, poorly differentiated tumor cells showed lower antioxidant enzyme staining intensities than well-differentiated tumor cells. Manganese-containing superoxide dismutase staining intensities were, however, higher in well-differentiated oral squamous cell carcinomas than their normal cells of origin. CONCLUSIONS: Detection of antioxidant enzymes may be a useful future marker in the molecular diagnosis of the oral cancer. Moreover, it may be possible to not only monitor the effectiveness of chemopreventive and therapeutic strategies in oral cancer using these enzymes, but to monitor tumor recurrence.     

Expression of TNF and the 55-kDa TNF receptor in epidermis, oral mucosa, lichen planus and squamous cell carcinoma

TNF has diverse biological effects including a role in the immune response and growth regulatory effects.
OBJECTIVES: The aim of this study was to determine the nature and location of cells able to synthesise and respond to TNF in oral mucosa in health and disease.
MATERIALS AND METHODS: The location of immuno-reactive TNF and 55-kDa and 7s-kDa TNF receptors was demonstrated using immunohistology. We also used RT-PCR to help determine the sites of synthesis of this cyto-kine in oral mucosa.
RESULTS: Only occasional TNF-positive cells were detected in normal epidermis and oral mucosa. However, this cytokine was found throughout the epithelia in oral lichen planus, leukoplakia and squamous cell carcinoma (SCC). The possible cellular sources and biological effects of TNF in these disease processes is discussed. The 55-kDa TNFR was expressed at the cell membrane throughout the epidermis, but confined to the lower cell layers on oral mucosa. Ten of 22 SCC did not express this receptor. A significant correlation was observed between the velocity of tumour growth and absence of TNF receptors.
CONCLUSIONS: The growth inhibitory and immuno-regulatory effects of TNF may be modulated by changes in receptor expression and alterations in synthesis of this cytokine in a subgroup of oral SCC.     

Possible involvement of stem cell factor and endothelin-1 in the emergence of pigmented squamous cell carcinoma in oral mucosa

We present here the clinical, morphological and immunohistochemical features of a pigmented squamous cell carcinoma (SCC) in the oral mucosa of the hard palate of a 76-year-old Japanese man. He underwent a partial resection of the maxilla subsequent to radiotherapy. The tumor was typical, moderately well-differentiated SCC but had many melanocytes (melanocytosis) within it. Immunohistochemical analysis for stem cell factor (SCF) and endothelin-1, both of which are known to stimulate proliferation and differentiation of melanocytes, revealed prominent expression of both factors in the neoplastic squamous cells of the pigmented SCC, while the non-pigmented oral SCC showed little sign of either factor. These findings strongly suggest that SCF and endothelin-1 secreted by neoplasmic squamous cells are involved in the emergence of a rare variant of oral SCC.     

Actual proliferating index in oral squamous cell carcinoma and leukoplakia

Aim: To examine the possible association between epithelial proliferation and disease progression in the oral mucosa using the actual proliferation index. Methods: The actual proliferation index was measured by the Ki‐67 labeling index and argyrophilic nucleolar organizer region count per nucleus. Immunohistochemistry was carried out for Ki‐67 by using the molecular immunology borstel‐1 clone in 20 leukoplakias, 20 oral squamous cell carcinomas, and 10 normal oral mucosae. Results: The argyrophilic nucleolar organizer region count per nucleus, Ki‐67 labeling index, and actual proliferation index were significantly higher in oral squamous cell carcinoma, followed by leukoplakia and normal oral mucosa. Leukoplakia with dysplasia showed a significantly higher Ki‐67 labeling index and actual proliferation index, compared to leukoplakia without dysphasia. There was a significant correlation of Bryne’s histological malignancy grading with the argyrophilic nucleolar organizer region count and the Ki‐67 labeling index. There was a significant positive correlation between the argyrophilic nucleolar organizer region count and the Ki‐67 labeling index among all groups. Conclusions: Leukoplakia or suspected epithelial dysplasia should be stained for argyrophilic nucleolar organizer regions and Ki‐67. The actual proliferation index is not only useful as a prognostic factor, but could also be a promising treatment determining modality for patients with premalignant and malignant lesions.     

Immunohistochemical evaluation of intermediate filament proteins in squamous papilloma and oral verrucous carcinoma

OBJECTIVE: Cytokeratins (CKs) are the intermediate filament proteins of the epithelium cells, which have become important markers of normal and abnormal cell differentiation. The goal of the present study was to investigate the expression pattern of CK 10, 13, 14 and 16 in oral verrucous carcinoma (OVC) and oral squamous papilloma (OSP). MATERIAL AND METHODS: Formalin-fixed paraffin-embedded sections from eight cases of each lesion were assessed. Immunohistochemistry was carried out using streptoavidin-biotin complex method. RESULTS: In OVC, CK 10 was expressed in suprabasal to superficial layers whereas in OSP mainly in superficial layer. CK 13 was detected in prickle and superficial cells in most cases of OVC and in suprabasal to superficial cells of OSP. All the cell layers of OVC reacted positively for CK 14 while basal and suprabasal layers of OSP were more pronounced for CK 14. Finally, CK 16 was observed in suprabasal to superficial layer in OVC and the majority cases in OSP showed only superficial reactive cells. CONCLUSIONS: CK 10, 13, 14 and 16 immunohistochemical profile emphasis the biological behavior of the studied lesions and confirm the use of these proteins as markers of differentiation.     

Age-specific and age-standardised incidence rates for intraoral squamous cell carcinoma in Blacks on the Witwatersrand, South Africa

All new cases of intraoral squamous cell carcinoma which occurred in Blacks resident on the Witwatersrand during the 10-yr period 1971-80 were traced by examining the records of all the hospital pathology departments in this area. The population at risk at the mid-point of the study (1975) was calculated from the National Population Censuses of 1970 and 1980, and consisted of 1125960 men and 880269 women. Age-specific incidence rates and age-standardised incidence rates were calculated for each intraoral site for men and women. In the latter calculation a standard World population was used. All rates are expressed as average number of cases per 100000 population per annum. The age-specific incidence rates and age-standardised incidence rates (in brackets) for men and women respectively are: tongue, 1.43 and 0.26 (2.69 and 0.41); gingiva and alveolar ridge, 0.04 and 0.01 (0.07 and 0.01); floor of mouth, 0.87 and 0.22 (1.64 and 0.38); buccal mucosa, 0.05 and 0.04 (0.13 and 0.05); hard and soft palate, 0.34 and 0.05 (0.63 and 0.08). There appears to have been an increase in the incidence of intraoral cancer in Black South Africans since the first survey in 1953-55, which can probably be ascribed to the urbanization process. In Europe, North America and in other population groups in South Africa, the palate is least frequently affected. In contrast, in Black South Africans lesions of the palate are much more common, being less frequent only than tongue and floor of mouth lesions.(ABSTRACT TRUNCATED AT 250 WORDS)     

EP—CAM在OLP和OSCC组织中的表达及意义

目的：观察上皮细胞黏附分子（Ep—CAM）在口腔正常黏膜、扁平苔癣（OLP）和鳞癌（OSCC）组织中表达的变化,分析Ep—CAM在口腔黏膜疾病及其癌变发病机制中的作用。方法：采用免疫组织化学法检测10例正常口腔黏膜、30例OLP（15例非糜烂型、15例糜烂型）及20例OSCC组织中Ep—CAM的表达变化。结果：Ep—CAM在正常黏膜组织阴性表达,而在非糜烂型OLP、糜烂型OLP及OSCC组织中表达逐渐增强。结论：Ep—CAM在口腔黏膜癌变的发展过程中可能具有一定的指示意义。     

Loss of Harvey ras heterozygosity in oral squamous carcinoma

This investigation of oral squamous carcinoma in five individuals revealed that four of the patients were constitutionally heterozygous at the c-Ha-ras-1 locus and that the tumour from one patient had lost that heterozygosity. The loss of c-Ha-ras-1 alleles provides a useful marker for detecting deletions of genetic material located on the short arm of chromosome 11 (11p) and has been found in association with a number of malignant tumours but has not been previously described in carcinoma of the head and neck. The repeated association of 11p deletions with malignancies has led to the postulation of a recessive cancer gene or tumour suppressor gene at this location involved in carcinogenesis and tumour progression. This study indicates that such a mechanism may contribute to the development of oral squamous carcinoma.     

Role of combined modality treatment of buccal mucosa squamous cell carcinoma

BACKGROUND: Squamous cell carcinoma of the buccal mucosa is an oral cancer reported as having a poor prognosis. In many patients combined modality treatment incorporating surgery and adjuvant radiotherapy should be considered best practice. METHODS: Patients treated for buccal mucosa squamous cell carcinoma were identified through the computer database in the Department of Radiation Oncology, Westmead Hospital, Sydney. All eligible patients were treated with curative intent. Survival was calculated using the Kaplan-Meier product limit method. RESULTS: A total of 32 eligible patients were identified. There were 20 males and 12 females. Median age at diagnosis was 67 years (range 44-82 years). Median duration of follow-up was 42 months (6-205 months). More than half (59 per cent) presented with early stage disease (stage I/II) with 35 per cent presenting with advanced (stage III/IV) disease. Most patients (28/32; 88 per cent) underwent surgery with eight patients also undergoing adjuvant radiotherapy. Four patients underwent definitive radiotherapy alone. A total of 15/32 (47 per cent) patients developed recurrence: four locally, eight regionally and three with locoregional recurrence. Patients treated with surgery and adjuvant radiotherapy had the lowest rate of recurrence. Median time to recurrence was five months. The three-year overall and disease free survival was 55 and 47 per cent, respectively. CONCLUSION: Buccal mucosa squamous cell carcinoma is an aggressive squamous cell carcinoma of the oral cavity. Despite treatment patients remain at risk of locoregional recurrence especially in the untreated ipsilateral neck. In many cases patients will benefit from multimodality treatment.     

Etiological factors in oral squamous cell carcinoma

A retrospective survey of 75 patients with oral squamous cell carcinoma (ICD Nos. 143, 144, 145) resident in the County Borough of Stoke-on-Trent, England, and 150 controls has been carried out by interview. The controls were matched for age, sex, occupation and place of residence. There was no difference in the prevalence or duration of denture wearing, although male controls had their dentures remade more frequently. Male patients practised oral hygiene procedures less frequently when they had their own teeth than controls. Habitual beer-drinking was more common and greater quantities were drunk by male patients than controls. Habitual cigarette smoking was less and pipe smoking greater among male patients than controls. Tobacco chewing, which was restricted to miners, was equally common (45%) in the two groups. Among miners, the combined habit of tobacco chewing and pipe smoking was more common among patients (1005) than among controls (25%).