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PubMed2004

Differential expression of the non-receptor tyrosine kinase BRK in oral squamous cell carcinoma and normal oral epithelium.

BRK is a non-receptor tyrosine kinase whose functional role is poorly understood. Although it is an epithelial specific kinase, its expression appears to be tissue specific. To date, little is known about BRK expression in human oral epithelium. We investigated expression of BRK in human oral squamous cell carcinomas (OSCC) and normal oral epithelium (NOE) using immunohistochemistry, laser confocal microscopy and Western blotting. The subcellular localization of BRK was identified by confocal microscopy and Western blotting of nuclear and cytoplasmic extracts from these cells. The results indicate that NOE express higher levels of BRK compared with OSCC cells. In NOE and moderately differentiated OSCC cells, BRK was localized in the nucleus and cytoplasm. However, in poorly differentiated OSCC cells, BRK was localized in perinuclear regions. These results suggest that BRK expression differs in normal and OSCC which may reflect a possible functional involvement in OSCC.

Blotting, Western↗
PubMed2005

Increased nitric oxide levels and iNOS over-expression in oral squamous cell carcinoma.

Inducible nitric oxide synthase (iNOS) is responsible for generating high levels of nitric oxide (NO) in tissues. Increased iNOS expression has been demonstrated in a number of carcinomas including head and neck squamous cell carcinoma (SCC). However, iNOS levels have not been evaluated specifically in oral cavity SCC, or in the precancerous lesions that progress to oral SCC. Also, NO levels have not been measured in oral precancerous or cancerous tissues. We therefore measured iNOS mRNA, iNOS protein and NO in oral SCC, oral dysplasias and normal oral epithelium. We used RT-PCR to quantify and compare iNOS mRNA levels in these oral tissue specimens. We found that iNOS mRNA was overexpressed in 41% of oral SCC but in only 8% of dysplasia specimens (P = 0.003). Immunohistochemistry was used to evaluate iNOS protein levels in oral SCC, oral dysplasias and normal oral epithelium. A significantly higher percentage of oral SCC specimens showed the highest level of iNOS staining relative to the oral dysplasias and normal oral epithelial samples (95% of oral SCC, 50% of dysplasias, and only 0% of normal epithelial controls, P < 0.0001). The positive staining for iNOS was limited to the SCC cells. Production of NO from iNOS was quantified using HPLC and found to be significantly higher in oral SCC (1.45 +/- 0.56 microg/ml) than normal epithelial controls (0.43 +/- 0.26 microg/ml) (P = 0.0013). We conclude that iNOS mRNA levels and NO production are significantly increased, in oral SCC compared to oral dysplasias and normal epithelial controls. These findings suggest that increased iNOS expression and the generation of high NO levels might have a role in oral SCC development.

Carcinoma, Squamous Cell↗
PubMed2005

Comparison of radial forearm free flap, pedicled buccal fat pad flap and split-thickness skin graft in reconstruction of buccal mucosal defect.

There are a variety of methods to reconstruct the mucosal defect after the ablation of buccal cancer. We used the radial forearm free flap (RFFF), pedicled buccal fat pad flap (PBFPF) or split-thickness skin graft (STSG) to reconstruct the buccal mucosal defect in our series respectively and compared the mouth-open width among these methods. We found there was no significant difference in the change of mouth-open width between the Group STSG and Group PBFPF. However, the negative effect on the mouth opening was significantly less (p<0.05) in Group RFFF when compared with the Group STSG or Group PBFPF. In conclusion, reconstruction with radial forearm free flap for buccal mucosal defect carries more chances to preserve the original mouth-open width than with pedicled buccal fat pad flap or split-thickness skin graft among the selected patients who undergo tumor resection for T2 or T3 buccal cancer.

Adult↗
PubMed2005

Toluidine blue uptake in potentially malignant oral lesions in vivo: clinical and histological assessment.

To assess the histological features of in vivo toluidine blue (TB) uptake in potentially malignant oral lesions (PML) and to determine whether any were related to clinical Dark versus Pale Royal Blue stain and/or to the malignant/dysplastic nature of the lesions. Frozen sections were used to evaluate TB extra- and intra-epithelial distribution, depth of penetration and nuclear or extra-nuclear uptake. Eighteen lesions were studied. The clinical appearance of a Dark Royal Blue stain was significantly related to the nuclear uptake of the dye. Conversely Pale Royal Blue staining was unrelated to any histological feature. Dark Royal Blue-malignant lesions had more nuclear uptake than benign lesions. The results suggest that Dark Royal Blue staining is the true positive outcome of a TB test and showed that Dark Royal Blue-malignant and Dark Royal Blue-benign lesions have a different histological pattern of uptake.

Carcinoma, Squamous Cell↗
PubMed2006

The cytotoxic effects of human neutrophil peptide-1 (HNP1) and lactoferrin on oral squamous cell carcinoma (OSCC) in vitro.

Alpha-defensin or human neutrophil peptide-1 (HNP1) is a neutrophil-derived antimicrobial peptide with cytotoxic effects towards cancer cells. Lactoferrin is also stored in human neutrophils and is a glycoprotein involved in mediating cytotoxicity towards tumour cells. This study investigated the sensitivity of normal oral keratinocyte and oral squamous cell carcinoma (OSCC) cells to HNP1 and lactoferrin in various combinations. A concentration of 100 microg/ml HNP1 induced the most significant cytotoxic effect on both normal and OSCC cells. Lactoferrin (12.5, 25 and 250 microg/ml) also significantly induced cell death in OSCC cells after 72 h. Of note, a combination of 10 microg/ml HNP1 and 50 microg/ml lactoferrin induced a differential effect, not observed with either concentration alone, which stimulated proliferation in normal cells, but induced cell death in OSCC cells throughout the study. These results indicate a potentially important co-operative role for HNP1 and lactoferrin in facilitating a selective cytotoxic effect on tumour cells.

Carcinoma, Squamous Cell↗
PubMed2006

Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation.

The aim of this paper is to assess the reproducibility of a novel binary grading system (high/low risk) of oral epithelial dysplasia and to compare it with the WHO classification 2005. The accuracy of the new system for predicting malignant transformation was also assessed. Ninety-six consecutive oral epithelial dysplasia biopsies with known clinical outcomes were retrieved from the Oral Pathology archives. A pilot study was conducted on 28 cases to determine the process of classification. Four observers then reviewed the same set of H&E stained slides of 68 oral dysplastic lesions using the two grading systems blinded to the clinical outcomes. The overall inter-observer unweighted and weighted kappa agreements for the WHO grading system were Ks = 0.22 (95% CI: 0.11-0.35), Kw = 0.63 (95% CI: 0.42-0.78), respectively, versus K = 0.50 (95% CI: 0.35-0.67) for the new binary system. Interestingly, all pathologists showed satisfactory agreement on the distinction of mild dysplasia from severe dysplasia and from carcinoma in situ using the new WHO classification. However, assessment of moderate dysplasia remains problematic. The sensitivity and specificity of the new binary grading system for predicting malignant transformation in oral epithelial dysplasia were 85% and 80%, respectively and the accuracy was 82%. The new binary grading system complemented the WHO Classification 2005 and may have merit in helping clinicians to make critical clinical decisions particularly for the cases of moderate dysplasia. Histological grading of dysplasia using established criteria is a reproducible prognosticator in oral epithelial dysplasia. Furthermore, the present study showed that more consensus scoring on either the degree of dysplasia, assessment of risk or the presence of each morphological characteristic by a panel should be encouraged.

Biopsy↗
PubMed2006

Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: an attempt to understand the sources of variation.

The present study attempted to assess the reasons behind the inter-observer variation in grading oral epithelial dysplasia (OED). Three oral pathologists and one general pathologist examined 68 histological slides of OED lesions of variable grade for scoring the presence of each individual characteristic of the architecture and cytology changes that were established by the 2005 WHO classification. The assigned features in each case were correlated with clinical outcomes to understand which features are more commonly associated with malignant transformation. Interestingly, for all individual characteristics, the pairwise inter-examiner and group kappa values ranged from poor to moderate. It appeared that for each characteristic separately there was much dissension. Despite these observations, comparing these data with that from our previous paper on the same slides showed that the inter-observer agreement on the degree of dysplasia either by using the new binary system of "low-risk" or "high-risk" or by using the 2005 WHO classification turned out to be better than the agreement on the individual characteristics of architecture and cytology changes. Certain features show significant association with the clinical outcomes. In the discussion, some explanations to help understanding the sources of variation in grading OED are put forward. In conclusion, grading dysplasia is not an exact science and pathologists are doing their best to reach optimal results. Improvement in the standard of the histopathology reporting of OED lesions could be achieved by consideration of several issues. Of these, there is need for a universal definition of the architectural and cytological features that are the basis of any OED grading process. A minimum dataset for reporting OED lesions should be set up. Also, the use of a consensus scoring process between two or more observers should be encouraged as this would improve inter-observer agreement.

Carcinoma in Situ↗
PubMed2006

Adenoid cystic carcinoma of the buccal vestibule: A case report and review of the literature.

Minor salivary gland tumors of the buccal vestibule are relatively rare. Adenoid cystic carcinoma is the fifth most common salivary gland malignancy following mucoepidermoid carcinoma, adenocarcinoma not otherwise specified (NOS), acinic cell adenocarcinoma and polymorphous low-grade adenocarcinoma (PLGA). Greater than half of adenoid cystic carcinomas occur in the parotid and submandibular glands. The most common intraoral site is the palate. Adenoid cystic carcinoma tends to have a protracted clinical course with wide infiltration and late distant metastases. We present a case of an adenoid cystic carcinoma of the buccal vestibule in a 59-year-old Caucasian female patient that she had been aware of for 15 years.

Carcinoma, Adenoid Cystic↗
PubMed2006

Areca nut extract treatment down-regulates involucrin in normal human oral keratinocyte through P13K/AKT activation.

Areca (betel) is an important etiological factor linked to the high prevalence of oral carcinoma and other oral diseases in South Asians. Involucrin is a key component of the cornified envelop and a differentiation marker of keratinocyte. In this study, we found that 5 microg/ml non-toxic areca nut extract (ANE) treatment resulted in the 0.5-fold down-regulation of involucrin and disruption in involucrin distribution in normal human oral keratinocyte (NHOK). Progressive down-regulation of involucrin during oral carcinogenesis was noted. Activation of AKT by 1.7-fold and up-regulation of COX-2 by 2-fold were elicited following ANE treatment in NHOK. Treatment with PI3K/AKT blockers reverted the down-regulation of involucrin. ANE also down-regulated involucrin by 0.6-fold and disturbed both cornified envelope and cell aggregation in calcium-induced differentiated NHOK. However, such phenomena seemed to be independent from the ANE-associated COX-2 activation. The ANE-associated down-regulation of involucrin through AKT pathway could underlie the areca-associated epithelial pathogenesis.

Adult↗
PubMed2006

A pilot case control study on the efficacy of acetic acid wash and chemiluminescent illumination (ViziLite) in the visualisation of oral mucosal white lesions.

Conventional screening practice for oral lesions involves visual scrutiny of the oral tissues with the naked eye under projected incandescent or halogen illumination. Visualisation is the principal strategy used to assess patients' lesions at risk for malignant transformation; hence, any procedure which highlights such lesions should aid the clinician. The aim of this pilot study was to examine the efficacy of acetic acid wash and chemiluminescent light (ViziLite) in enhancing visualisation of oral mucosal white lesions, and its ability to highlight malignant and potentially malignant lesions. Fifty five patients referred for assessment of an oral white lesion, were prospectively screened with ViziLite, and an incisional scalpel biopsy performed for a definitive diagnosis. The size, location, ease of visibility, border distinctness, and presence of satellite lesions were recorded. The ViziLite tool enhanced intra-oral visualisation of 26 white lesions. Indeed, all lesions appeared "aceto-white", regardless of the definitive diagnosis. Examination of the oral tissues with ViziLite illumination did not change the provisional diagnosis, nor alter the biopsy site. ViziLite illumination does not discriminate between keratotic, inflammatory, malignant or potentially malignant oral mucosal white lesions and thus, a high index of suspicion, expert clinical judgment, and scalpel biopsy are still essential for proper patient care.

Acetic Acid↗
PubMed2006

Pathology of malignant and premalignant oral epithelial lesions.

Oral mucous membranes and the surrounding structures are largely composed of stratified squamous epithelium that is supported by a fibrous connective tissue lamina propria and a submucosa of fibroadipose tissue. Minor salivary glands, nerves, and capillaries course abundantly throughout the supporting collagen and fibro-fatty submucosa. Premalignant and malignant lesions arise most frequently from epithelium, and these epithelial lesions ultimately account for 95% of all cancers of the oral cavity. Malignant neoplasia of bone, cartilage, salivary glands, and connective tissue and those of lymphoproliferative derivatives are far less common occurrences in the oral cavity. Malignant neoplasms can and do arise from the tooth germ apparatus, but neoplasms of odontogenic elements are rare and are not included in this discussion.

Carcinoma in Situ↗
PubMed2006

The surgical management of oral cancer.

Oral cavity cancers represent an area of head and neck oncology with some unique and interesting management themes. In spite of a significant paradigm shift in the treatment of many head and neck cancers toward us-ing primary chemoradiation, this treatment is not frequently applied to the oral cavity. Small cancers of the oral cavity are usually managed by surgery alone. Larger cancers are usually treated with primary surgery followed by chemoradiation. Neck treatment is offered to patients who have a greater than 20% chance of having lymph node metastasis or who have neck disease at the time of presentation. Neck treatment may involve surgery, radiation therapy, or both. Reconstruction of surgical defects of the oral cavity runs the gamut of techniques from the most simple to the most complex three-dimensional microvascular composite flaps. A multidisciplinary setting with a tumor board and multiple supportive services provides the best care for patients who have advanced-stage cancers.

Brachytherapy↗
PubMed2006

Early diagnosis of oral cavity cancers.

Dentists, primary care physicians, and otolaryngologists should continue to perform complete oral cavity examinations and should be aware of high-risk populations for oral cavity carcinomas. Oral cavity carcinoma is the sixth most common cancer and is often detected in later stages. By using the modalities of physical examination, brush biopsies, vital staining, and spectral analysis, it is hoped that more cancers will be detected at an early stage, decreasing the morbidity and mortality of oral cavity tumors.

Carcinoma, Squamous Cell↗
PubMed2007

Impact of recurrence interval on survival of oral cavity squamous cell carcinoma patients after local relapse.

OBJECTIVE: The aim of this study was to investigate whether the recurrence interval influenced the survival of oral cavity squamous cell carcinoma patients after relapse. STUDY DESIGN AND SETTING: Retrospective charts were reviewed at a medical center. METHODS: We retrospectively reviewed 1687 chart records of oral cancer patients. Statistical methods included descriptive statistics, bivariate analyses, Kaplan-Meier survival analyses, and Cox proportional hazard models for investigating the relationship between the recurrence interval and survival of oral cancer patients after relapse. RESULTS: Local recurrence rate was 31.3 percent. Kaplan-Meier survival analyses showed the 5-year overall survival after recurrence was 31.56 percent. Cox proportional hazard model revealed that those with recurrence interval less than 18 months tended to have a higher probability of death than those with recurrence interval greater than or equal to 18 months (relative risk, 1.743; 95% confidence interval, 1.298-2.358). CONCLUSION: The interval from initial treatment to recurrence is an independent prognostic factor for oral squamous cell carcinoma patients. Those with a shorter disease-free interval tend to have a less favorable outcome.

Adult↗
PubMed2005

Buccal mucosal transposition flap for reconstruction of oropharyngeal-oral cavity defects: an analysis of six cases.

BACKGROUND: Operation on tumors situated in the posterior part of the oral cavity is a challenging aspect of head and neck surgery. Both the approach and the postablative reconstruction of the remaining defect require special procedures. An arsenal of reconstructive methods are available depending on the size and complexity of the defect. The goal should be to employ the simplest surgical reconstructive method, resulting in the best functional result and allowing for later complex oncotherapy. OBJECTIVE: To study the outcomes of patients treated using buccal mucosal transposition flaps for reconstruction of posterior oral cavity and oropharyngeal border defects. STUDY DESIGN: A total of 6 patients with defects of the posterior oral cavity and mesopharynx were treated with buccal mucosal transposition flaps. The patients were followed for up to 24 months. RESULTS: Defects ranging from 12 to 27 cm 2 were reconstructed with the buccal mucosal transposition flap. One patient developed an orocutaneous fistula and 1 had some trismus requiring a Z-plasty scar reorientation. One patient suffered from nasal regurgitation. Five of the 6 patients lived past 24 months, the time of follow-up of this study. CONCLUSIONS: The buccal mucosal transposition flap, with its random pattern of circulation, used alone proved to be a safe method to reconstruct soft tissue defects or line exposed hard tissues located in the posterior oral cavity and oropharynx.

Adult↗
PubMed2005

Transformation of a benign oral pigmentation to primary oral melanoma.

OBJECTIVE: The objective is to report the serendipitous 7-year follow-up and transformation of a melanotic palatal lesion, which was initially diagnosed histologically as a benign oral melanotic macule, into primary oral melanoma and to provide long-term follow-up of a case of oral malignant melanoma. STUDY DESIGN: Nine formalin-fixed paraffin-embedded tissue blocks from several different facilities and microscopic slides of the patient's lesions were reviewed to study the transformation of a benign, oral, pigmented lesion into melanoma. RESULTS: Review of blocks and slides of the patient's lesions suggest that the onset of melanocytic hyperplasia (increased clear cell activity) heralded the transformation of the melanotic macule into melanoma. The histology of the first biopsies was totally benign, but retrospectively, the clinical appearance was not typical and was somewhat worrisome because of the size of the lesion and feathering of the pigmentation at the periphery. This clinical presentation, however, was unknown to the pathologists. CONCLUSIONS: This study documents a case of primary oral melanoma arising from an apparent oral melanotic macule and suggests that even histologically benign-appearing oral melanotic lesions should perhaps be viewed with caution if increased numbers of melanocytes (melanocytic hyperplasia or clear cell activity) are present. Careful correlation of clinical appearance and histology is necessary to arrive at an appropriate diagnosis and prognosis for oral pigmented lesions.

Adult↗