Cytokeratin expression in oral cancer and its relationship to tumor differentiation

Although cytokeratin expression is said to alter with the state of tumor differentiation, few studies appear to have confirmed this in fresh tissues biopsies from oral squamous cell carcinomas. Previous studies have been limited by the number of antibodies utilized, small sample size, or lack of information regarding tumor differentiation. A panel of 8 antikeratin antibodies (of which five recognised the simple epithelial karatins, 8. 18 and 19) were applied to fresh tissue biopsies from 24 oral cancer and 15 normal oral mucosal biopsies. A standard immunocytochemical technique was followed (Vectastain Abc Method), with keratin expression graded on a 3 point scale. Our analysis indicated that simple epithelial keratins (K8. K.I8, K19) were not confined to the more poorly differentiated tumors. This may be relevant to tumor prognosis.     

Metallothionein and p-Akt proteins in oral dysplasia and in oral squamous cell carcinoma: an immunohistochemical study

Background:  Oral leukoplakia (OL) is the main potentially malignant lesion of the oral cavity, and oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of p-Akt and Metallothionein (MT) proteins in dysplasic and neoplasic oral lesions.
Methods:  Immunohistochemical studies were carried out on 10 normal epithelium, 30 OL and 15 OSCC paraffin-embedded samples. Immunoperoxidase reaction for p-Akt and MT proteins was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells.
Results:  Using the ANOVA and the Tukey's post hoc statistical analyses, it was observed a significant difference in the immunoexpression for p-Akt and MT when the OSCC samples were compared with normal and dysplasic epithelial groups. In addition, the Pearson's correlation test showed a significant correlation between the proteins' expression.
Conclusion:  Based on the data obtained, p-Akt and MT activation may play an important role in the conversion of a potentially malignant oral lesion to a malignant carcinoma since its earlier stages.     

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口腔黏膜癌前病变与口腔癌的发生密切相关,是口腔医学研究领域的重要课题之一。临床上口腔黏膜癌前病变主要有白斑和红斑,1979年的WHO口腔癌前病变的临床分类中还包括与倒吸烟相关的角化症。与上述癌前病变相关的还有一组所谓的癌前状态,如扁平苔藓等。众所     

Human papillomavirus DMA in oral squamous cell carcinomas and normal mucosa

Human papillomavirus (HPV) infections in oral carcinomas and normal oral mucosa were studied by consensus primer screening and typing for HPV types 6/11,16 and 18 DNA. After polymerase chain reaction (PCR) the DNA species of interest were identified by Southern blot hybridization with digoxigenin-labeled oligonucleotide probes. Frozen tissue and scrapings were equally suitable for HPV testing and yielded high HPV detection rates in carcinomas. By comparison, HPV analysis of paraffin-embedded material was much less efficient. HPV were demonstrated in 61.5% (16/26) of oral squamous cell carcinomas, high risk HPV 16 and 18 being the preferential types. The frequency of HPV detection in non-neoplastic mucosa of tumor patients decreased clearly with increasing distance from the tumor (range 26.9–3.8%) suggesting focal HPV infections. In contrast, normal buccal mucosa of a group of healthy volunteers contained HPV DNA only in 1%(1/97).     

Morphometric computer‐assisted image analysis of oral epithelial cells in normal epithelium and leukoplakia

J Oral Pathol Med (2010) 39 149–154 Background: There are very few studies documenting morphometric parameters of normal oral mucosa and leukoplakia. The present study was undertaken to establish the morphometric parameters of the parabasal and spinous cells of normal oral epithelium. Analysis of changes occurring in these cells in leukoplakia was also done. Methods: This study was conducted on tissue sections of clinically normal oral mucosa and leukoplakia. Morphometric analysis was done for parabasal and spinous cells. Statistical analysis was done using one way ANOVA and Mann–Whitney test. Results: Morphometric parameters were greater in the spinous cells than in parabasal cells in normal oral mucosa. Leukoplakia showed greater cellular and nuclear parameters than normal mucosa. Conclusion: Normal oral epithelium showed site‐wise difference in cell and nuclear measurements. Nuclear parameters showed a statistically significant change than cellular parameters in dysplasia. These changes were expressed in the earliest stage of transformation to dysplasia.     

Clinicopathological features and malignant transformation of oral lichen planus: A 12-years retrospective study

Abstract

Objective. Oral lichen planus (OLP) is known to be associated with the risk of developing oral squamous cell carcinoma (OSCC). The objective of this study was to investigate the clinicopathological features of OLP and the prevalence of malignant transformation in this setting. Materials and methods. This retrospective study was carried out on 204 medical records of patients with histologically proven OLP who received long-term follow-up (range 6 months–12 years). Data were entered in an informatic database. The statistical analysis, when needed, was performed with the chi-squared test for significance (p < 0.05). Results. At the moment of the diagnosis, out of 204 patients (163 female and 41 male; mean age 54.5 years), 107 patients (52.45%) suffered from systemic chronic diseases, in particular 46 (22.5%) from hepatitis C. Clinically, the reticular form of OLP was the predominant one and most patients had multiple oral sites of involvement. Fourteen patients showed extra-oral lesions. A percentage of malignant transformation less than 1% was found. In fact, two patients (0.98%) underwent a malignant transformation at a site previously diagnosed as OLP. Conclusions. At present, OLP is accepted as being a potential malignant disorder, therefore lifelong follow-up is recommended.     

A long-term follow-up study on the natural course of oral leukoplakia in a Swedish population-based sample

AIM: To assess the natural course of screening-detected oral leukoplakia (OL) among non-consulting individuals. METHODS: A cohort of 555 individuals with OL, confirmed in 1973-1974 during a population-based survey, were followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 104 drawn from the 297 surviving cohort members who still were living in the area in 1993-1995 was invited to a re-examination. Sixty-seven of them attended. RESULTS: At the time of re-examination OL had disappeared in 29 (43%) individuals. There was a statistically significant association between cessation of/no smoking habits in 1993-1995 and the disappearance of OL. Never/previous daily smokers were thus over-represented among individuals whose OL had disappeared compared to those with persisting OL [n = 23 (82%) vs. n = 18 (47%), P < 0.01]. Eighteen (78%) of the twenty three non-smokers with disappearing OL had quit after the initial examination. One man and two women developed oral cancer during follow-up while 0.7 and 0.07, respectively, were expected. CONCLUSION: Smoking cessation was associated with an increased disappearance of OL. Hence, at least one-fourth had lesions that could be classified as tobacco-related. Small observed and expected numbers prohibited firm conclusions about a possible excess risk of developing oral cancer.     

Photodynamic therapy of oral cancer A review of basic mechanisms and clinical applications

Photodynamic therapy (PDT) is an experimental cancer treatment modality. PDT is based on the accumulation of a photosensitive dye in premalignant and malignant lesions. A certain period of time after the dye has been administered, tumor tissue may contain more of the sensitizer then the surrounding normal tissues. When tissue containing the sensitizer is exposed to light of a proper wavelength and dose, a photochemical reaction between sensitizer and light will occur. The activated photosensitizer reacts with available oxygen which subsequently damages cells and eventually may cause necrosis of the tumor. Photosensitizers can also be used for fluorescence detection. If a tumor contains more of the photosensitizer than the surrounding normal tissue, its fluorescence can potentially be utilized to detect tumors. Analogous to PDT, this can therefore be referred to as photodynamic detection (PDD). This paper reviews the basic mechanisms and clinical applications of PDT and PDD. Emphasis is placed on PDD and PDT with the photosensitizer Photofrin for detection and treatment of premalignant epithelial lesions and squamous cell carcinomas of the oral mucosa.     

Leukoplakia and incidence of oral cancer

Reports from India showing comparatively lower prevalence rates of oral leukoplakia and lower malignant transformation rates than in western countries appear paradoxical because of high incidence rates of oral cancer in India. On a closer examination of available data however, it becomes clear that there is no inconsistency.     

On the natural course of oral lichen lesions in a Swedish population-based sample

OBJECTIVES: The aim was to assess the natural course of oral lichen lesions (OLL) among unselected, non-consulting individuals. SUBJECTS AND METHODS: A cohort of 327 subjects with OLL, confirmed in 1973-1974 during a population-based survey in two Swedish municipalities, was followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 80 drawn from the 194 surviving subjects who still resided in the area in 1993-1995 was invited for interview and oral re-examination. RESULTS: At the end of follow-up, one case of oral cancer was detected, while 0.4 were expected. The overall mortality among subjects with OLL was not significantly different from that in the 15,817 OLL-free subjects who participated in the initial population based survey in 1973-1974. The lesion had disappeared in 14 (39%) of 36 re-examined subjects with white OLLs in 1973-1974, and four (11%) had transformed into red types. In the corresponding group of 19 with red forms initially, five (26%) had become lesion free and four (21%) had switched to white types. Although the cohort size does not permit firm conclusions regarding oral cancer risk, the natural course over up to 30 years appears to be benign in the great majority.     

Detection of survivin mRNA in healthy oral mucosa, oral leucoplakia and oral cancer

Background:  Survivin is involved in modulation of cell death and cell division processes. Survivin expression in normal adult tissues has not been fully understood, although it is markedly lower than in cancer, where it is over-expressed.
Objective:  To investigate survivin expression in normal, potentially malignant and cancerous oral mucosa.
Methods:  We measured survivin mRNA levels by real-time RT-PCR in specimens of oral mucosa (15 from normal mucosa, 17 from potentially malignant lesions, 17 from neoplasms). Scores were compared using Kruskal–Wallis test and post hoc according to Conover. Chi-squared test was used for dichotomous data.
Results:  The median relative levels of survivin mRNA resulted six for normal mucosa, eight for potentially malignant lesions, 13 for cancers: differences among these three groups were statistically significant, as between cancer and potentially malignant lesions. Expression in normal mucosa and potentially lesions group showed no significant difference. Low, but not marginal expression of survivin in normal mucosa is a new finding, and it could be explained with the higher sensibility of our methods.
Conclusions:  Survivin expression in oral potentially malignant lesions might indicate a progressive deregulation of expression paralleling oncogenesis, particularly during the first stages of process, suggesting a putative predictive role for survivin.     

The role of ascorbic acid in oral cancer and carcinogenesis

L-ascorbic acid is an essential dietary vitamin in humans, primates and certain mammals and is endogenously syn-thesised in some species. Epidemiological and ecological studies have shown that L-ascorbic acid has a protective effect against cancer, in particular non-hormone-dependent malignancies, such as oropharyngeal neoplasms. Experimental in vivo and in vitro studies, however, have yielded more controversial results, suggesting that the effects of L-ascorbic acid are dose- and perhaps, time-dependent with different effects depending on the species or organ studied. An update of the epidemiological and experimental evidence linking L-ascorbic acid to oral cancer and carcinogenesis is discussed together with a brief review of the possible mechanisms of action of L-ascorbic acid.     

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.     

Minocycline and oral pigmentation

Minocycline is a semisynthetic tetracycline used in the treatment of inflammatory acne because of its broad spectrum of activity, less common development of resistant organisms, and its anti-inflammatory effects. A number of adverse reactions are reported, including skin and oral pigmentation. This paper details the pharmacology of minocycline and describes the pigmentation and likely mechanisms active in both hard and soft tissues. Oral pigmentation usually involves the hard tissues only and presents typically as a discrete band occupying the central zone of the alveolar mucosa and palate. As with other sites, it may persist following withdrawal of the drug. Early recognition by the dental practitioner may allow an alternative form of therapy to be sought, minimizing the likelihood of a longterm aesthetic problem.     

Tissue markers of potentially malignant human oral epithelial lesions

Tissue markers of potential malignancy have been sought for many years. Cell surface markers, particularly blood group and histocompatibility antigens, have shown great promise and several squamous carcinoma antigens have been identified - but not fully studied in potentially malignant lesions. Growth factors and receptors also need further study. Cytoplasmic markers of potential malignancy have been examined and, of these, keratins, filaggrin, and some carcinoma antigens show most promise. Nuclear analyses have promise but are time-consuming and expensive. Image cytometric analyses appear to be sensitive and predictive: oncogene and tumour suppressor analyses remain to be fully evaluated. New investigative techniques at the cellular and molecular level show increasing promise at defining potentially malignant oral epithelial lesions but more prospective studies arc required.