Immunohistochemical evaluation of hedgehog signalling in epithelial/mesenchymal interactions in squamous cell carcinoma transformation: a pilot study

Precancerous lesions have been studied because of their carcinogenic potential and their association with squamous cell carcinoma (SCC) has been reported. In the tumour microenvironment, the processes of angiogenesis and tissue remodelling are regulated by a family of proteins (Hedgehog) described as being able to modulate epithelial/mesenchymal interactions. The objective of this study was to perform a comparative study of precancerous lesions and SCCs by immunohistochemistry for the presence of Sonic, Gli2, SMO and Patched proteins, members of the Hedgehog pathway. Sixteen cases diagnosed as actinic cheilitis associated with SCC were compared to normal oral mucosa. The sections were subjected to immunohistochemistry and the positively stained cells were counted by morphometric analysis. There was a significant progressive increase in expression of all proteins of the Hedgehog pathway, both in the epithelium and in the connective tissue, when sections of normal mucosa, dysplasia and carcinoma were compared (P < 0.05). Thus, one may suggest that the Hedgehog pathway in tumour transformation influences SCC, and more studies should be conducted to expand the understanding of the role of these proteins in neoplastic transformation.     

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口腔疾病患病率和发病率特别高,是主要的公共卫生问题之一。特别在社会低收入人群中,口腔疾病已经成为主要的疾病负担之一。本文就我国口腔流行病学资料,对我国目前口腔疾病的现状、改变的趋势、发展及对策做一论述和探讨。     

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.     

Microorganisms in recurrent aphthous ulcerations

abstract – Qualitative and quantitative examinations of the cultivable bacterial flora in biopsies from recurrent aphthous ulcerations (RAU), experimental oral ulcerations (EOU), and normal oral mucosa (NOM) were carried out under aerobic and continuous anaerobic conditions. An attempt was made to culture yeasts, mycoplasma, and virus from the biopsies of RAU, which were also tested for the presence of herpes virus antigen by the fluorescent antibody method. The predominant bacteria recovered in RAU were α-hemolytic streptococci, coagulase-negative staphylococci, and Neisseria . In EOU the main recoveries were α-hemolytic streptococci, Corynebacterium, Veillonella, Neisseria , and Haemophilus . In NOM α-hemolytic streptococci dominated the cultures. Yeasts were only cultured from one patient with RAU. No mycoplasmas or viruses were isolated, nor was herpes virus antigen demonstrated in any of the RAU specimens. The role of the microorganisms in the pathogenesis of RAU is discussed.     

Exfoliative cytology in clinical oral pathology

Exfoliative cytology is a rapid, non-invasive procedure for assessing dysplastic change within the oral epithelium. The indications for oral exfoliative cytology are reviewed and a technique for cell collection and smear examination is presented. The value of exfoliative cytology in oral cancer screening programmes as a public health measure is discussed.     

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.     

Epstein–Barr virus prevalence in oral squamous cell cancer and in potentially malignant oral disorders in an eastern Hungarian population

We tested 65, 44, and 116 patients with oral squamous cell cancer (OSCC), oral leukoplakia (OL), and oral lichen planus (OLP) against 68 age-matched controls for the presence of Epstein–Barr virus (EBV). Apparently healthy mucosa was simultaneously sampled and examined in all patients. Paraffin-embedded tissue sections of all EBV-positive patients with OSCC were examined for latent membrane protein-1 (LMP-1) expression (demonstrable in most EBV-associated malignancies) using immunohistochemistry. The prevalence of EBV in the controls and in OSCC, OL, and OLP lesions was 19.1%, 73.8%, 29.5%, and 46.6%, respectively, and 66.2%, 22.7%, and 31.9% in the healthy mucosa of patients, respectively. The prevalence of EBV in OSCC patients was significantly higher than in controls or in respective samples of the other two patient groups both in the lesion and in the healthy mucosa. Comparisons including only patients with EBV-negative lesions yielded similar results. Lesions of patients with OLP, but not of patients with OL, differed significantly from controls in EBV prevalence. In OSCC, LMP-1 expression was not detected, and EBV carriage was not significantly associated with any risk factors and did not influence the outcome. Although a high prevalence of EBV was found in OSCC, comparable carriage rates on healthy mucosa of patients indicated that an aetiological role of EBV is unlikely.     

The oral mucosa: A barrier site participating in tissue‐specific and systemic immunity

In the oral cavity, the immune system is constantly exposed to unique tissue‐specific signals, including a rich community of commensal microbes and their metabolites, continuous tissue damage from mastication, and antigens from food and airborne particles. How this unique combination of signals participates in the training of specialized immunity at this site is not well understood, yet imbalance of local responses is linked to tissue‐specific disease susceptibilities with the prototypic disease being periodontitis. However, the oral mucosa is also well recognized as a site where systemic inflammatory and autoimmune diseases often manifest, indicating that systemic immune deregulation is reflected in the function of the oral immune system. This commentary will discuss both aspects of compartmentalized and systemic immunity at the oral mucosa.     

A national epidemiological survey of oral mucosal lesions in Malaysia

Abstract The prevalence of oral mucosal lesions in Malaysia was determined by examining a representative sample of 11 707 subjects aged 25 years and above throughout the 14 states over a period of 5 months during 1993/1994. A two-stage stratified random sampling was undertaken. A predetermined number of enumeration blocks, the smallest population unit in the census publication was selected from each state. With the selected enumeration block, a systematic sample of living quarters was chosen with a random start. The survey instrument included a questionnaire on sociodemographic characteristics and a clinical examination. The clinical examination was carried out by 16 specially trained dental public health officers and the diagnosis calibrated with a final concordance rate of 92%. The age in the sample ranged from 25 to 115 years with a mean of 44.5+14.0. The sample comprised 40.2% males and 59.8% females; 55.8%. were Malays, 29.4% Chinese,10.0% Indians and 1.2% other ethnic groups. Oral mucosal lesions were detected in 1131 (9.7%.) subjects. 5 (0.04%) had oral cancer, 165 (1.4%) had lesions or conditions that may be precancerous (leukoplakia. erythroplakia, submucous fibrosis and lichen planus) and 187 (1.6%) had betel chewer's mucosa. The prevalence of oral precancer was highest amongst Indians (4.0%) and other Bumiputras (the indigenous people of Sabah and Sarawak) (2.5%) while the lowest prevalence was amongst the Chinese (0.5%).     

Oral mucosal lesions in patients with COVID-19: a systematic review

COVID-19 is a new disease that presents mainly with respiratory symptoms. However, it can present with a multitude of signs and symptoms that affect various body systems and several oral manifestations have also been reported. We carried out a systematic review to explore the types of oral mucosal lesions that have been reported in the COVID-19-related literature up to 25 March 2021. A structured electronic database search using Medline, Embase, and CINAHL, as well as a grey literature search using Google Scholar, revealed a total of 322 studies. After the removal of duplicates and completion of the primary and secondary filtering processes, 12 studies were included for final appraisal. In patients with COVID-19 infection, we identified several different types of oral mucosal lesions at various locations within the oral cavity. Most of the studies appraised had a high risk of bias according to the Joanna Briggs Institute checklist. The current published literature does not allow differentiation as to whether the oral lesions were caused by the viral infection itself, or were related to oral manifestations secondary to existing comorbidities or the treatment instigated to combat the disease. It is important for healthcare professionals to be aware of the possible link between COVID-19 and oral mucosal lesions, and we hereby discuss our findings.     

Malignant transformation of oral leukoplakia in a well‐defined cohort of 144 patients

Objectives

Oral leukoplakia is a potentially malignant disorder of the oral mucosa. The aim of this retrospective study was to identify the factors that possibly predict malignant transformation in a well‐defined cohort of patients with a long‐term follow‐up. All leukoplakias were staged according to a clinicopathological classification and staging system. Furthermore, a certainty factor has been used with which the diagnosis has been established.

Material and methods

The group consisted of 144 patients. The size, presence and degree of epithelial dysplasia were incorporated into a clinicopathological classification and staging system. Initial management consisted of surgical excision, CO₂ laser vaporisation or observation only. The mean follow‐up period was 51.2 months (s.d. = 39.33, range 12–179 months).

Results

In 16 of 144 patients (11%), malignant transformation occurred between 20 and 94 months (mean 57.0 months) after the first visit, the annual malignant transformation rate being approximately 2.6%. A large size of the lesion (≥ 4 cm) showed to be the only statistically significant predictor of malignant transformation (P = 0.034).

Conclusion

A size of ≥ 4 cm showed to be the only significant predicting factor of malignant transformation in oral leukoplakia. No other epidemiological, aetiological, clinical or histopathological parameters were of statistical significance.     

Epstein-Barr virus in tobacco-induced oral cancers and oral lesions in patients from India

D'Costa J, Saranath D, Sanghvi V, Mehta AR: Epstein-Barr virus in tobacco-induced oral cancers and oral lesions in patients from India. J Oral Pathol Med 1998; 27: 78–82. © Munksgaard, 1998.
We examined 103 oral squamous cell carcinomas (OSCC), 100 oral lesions consisting primarily of leukoplakia (82 cases), and 76 clinically normal mucosa specimens from the contralateral site in the oral cavity of individuals with oral lesions, for the presence of Epstein-Barr virus (EBV). Polymerase chain reaction (PCR) was used to amplify a 239 bp fragment of the BamHIL region of the EBV genome, followed by Southern blot hybridization with EBV oligonucleotide probe to increase further the specificity and sensitivity of the assay system. Since EBV seropositivity is frequent in populations, we also examined the peripheral blood cells (PBC) from 141 patients (50 oral cancer patients, 91 patients with oral lesions) for the presence of EBV We detected EBV in 25 of 103 (25%) OSCC, 13 of 100 (13%) oral lesions, 3 of 76 (4%) clinically normal mucosa samples and 10 of 141 (7%) PBC. Our results indicate that EBV may contribute as one of the multiple factors in oral cancers, in a certain proportion of Indian patients.     

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.     

The distribution of oral mucosal pH values in healthy saliva secretors

OBJECTIVES: To establish the normal range of oral mucosal pH and to correlate these measurements to salivary flow rate in healthy individuals according to age and gender. SUBJECTS AND METHODS: Measurements of pH levels using a flat pH meter and salivary secretion rates were established in eight mucosal sites from a total of 50 healthy individuals. RESULTS: The mean pH (+/-s.d.) of all sites was 6.78 +/- 0.04 with significant differences between mean pH values in the palate (7.34 +/- 0.38), the floor of the mouth (6.5 +/- 0.3), the buccal mucosa (6.28 +/- 0.36) and the tongue (6.8 +/- 0.26). A significant correlation was found between age and pH at palatal and tongue sites but no gender effects were noted. CONCLUSIONS: This method is easy and relatively quick to manipulate, and may offer many diagnostic possibilities for oral related diseases and disorders such as oral malodour, mouth breathing, dysgeusia, acidic diet consumption and gastrointestinal disorders affecting the mouth.     

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.