Malignant transformation of oral verrucous leukoplakia: a clinicopathologic study of 53 cases

J Oral Pathol Med (2011) 40 : 312–316 Background: Oral verrucous leukoplakia (VL) is one of the non‐homogenous oral leukoplakias. The objective of this study was to investigate the clinicopathologic features of VL and identify the clinicopathologic risk factors that might be associated with VL malignant transformation from China. Methods: Among 1541 patients with oral leukoplakia, a total of 53 patients with clinical and histopathologic diagnosis of VL between 1996 and 2009 were reviewed retrospectively in our hospital. Results: Of the 53 patients, 11 (20.8%) with VL were observed to develop cancer in the study period. The average age at diagnosis was 59.8 years with a male/female ratio of 1.7:1. Tongue was the predominant site (41.5%). Multivariate regression analysis revealed that the elderly patients (>65 years old) were associated with 8.36‐fold [95% confidence interval (95% CI), 1.45–48.09; P = 0.017] increased risk of malignant transformation compared with the non‐elderly patients. The lesion located on gingiva was associated with 20.81‐fold (95% CI, 1.94–222.80; P = 0.012) increased risk of malignant transformation compared with tongue. However, the gender, smoking, alcohol intake, and epithelial dysplasia were not risk factors. Conclusion: Clinicopathologic features of VL in China were elucidated. The utilization of age and lesion site at diagnosis as significant factors for evaluating malignant transformation risk in patients with VL was suggested. Further studies are required to investigate the roles of the potential risk factors in the VL malignant transformation.     

Role of TP53 in the progression of pre-malignant and malignant oral mucosal lesions. A follow-up study of 144 patients

Background:  Prediction of progression from pre-malignant oral mucosal lesions to malignancy, or recurrence of an existing oral squamous cell carcinoma (OSCC), is an important clinical problem in oral medicine.
Methods:  This study presents a follow-up of a study published in 2002. Samples from 54 patients with OSCC, 45 with oral lichen planus (OLP) and 45 with hyperkeratosis (clinically leukoplakia), diagnosed between 1987 and 1996, were analysed for TP53 protein expression and TP53 mutation. Follow-up was 11–17 years for OSCC (mean 13.3), 12–22 years for OLP (mean 15.9) and 12–17 years for hyperkeratosis (mean 14.5).
Results:  Of the 54 OSCC patients, 28 experienced recurrent disease, 21 died of OSCC, 22 died of other causes. Of the 14 OSCC patients with mutated TP53 ( n  = 11), the cancer recurred in eight (57%) and in 20/39 (51%) without mutation. Expression of TP53 protein was significantly associated with reduced overall survival. Among OLP patients, nine were TP53- mutated out of 31 tested. One TP53- mutated OLP patient developed OSCC in a different site. Of the hyperkeratosis patients, three were mutated of 22 tested. One hyperkeratosis patient (non-mutated) developed OSCC in the same site.
Conclusion:  TP53 mutations can exist in benign oral mucosal lesions for many years without progression to malignancy. No association was found between TP53 protein expression or TP53 mutation and recurrence of OSCC or disease-related survival. Overall survival was reduced in patients with positive TP53 protein expression.     

Significance of myofibroblasts in oral squamous cell carcinoma

J Oral Pathol Med (2011) 40 : 201–207 It is now recognized that the tumor microenvironment makes significant contribution to tumor progression. Activated fibroblast endothelial cells, inflammatory cells, and various extra cellular matrix components are parts of this microenvironment. Most of the activated fibroblasts are α‐smooth muscle actin–positive myofibroblast that often represent the majority of tumor stromal cells. Their production of growth factors chemokines and extracellular matrix facilitates tumor growth. Myofibroblast have been demonstrated in close to 50% of oral squamous cell carcinomas. In this review, we highlight the histological distribution of myofibroblast in oral squamous cell and the myofibroblast relation to tumor growth on prognosis.     

hMLH1 immunoexpression is related to the degree of epithelial dysplasia in oral leukoplakia

J Oral Pathol Med (2011) 40 : 153–159 Background: hMLH1 is a protein of the mammalian mismatch repair system responsible for genomic stability during repeated duplication. Relation between its altered expression linked to microsatellite instability has also been observed in oral leukoplakias (OL) and squamous cell carcinomas pointing to a possible role of hMLH1 in oral carcinogenesis. To our knowledge, this is the first study evaluating the immunoexpression of hMLH1 in OLs regarding their different degrees of epithelial dysplasia. Methods: Sixty‐two specimens of OL were classified in four groups: 17 without dysplasia, 19 with mild dysplasia, 16 with moderate dysplasia, and 10 with severe dysplasia. Immunohistochemistry for hMLH1 was performed, and percentage of positive cells was assessed. In the statistical analysis, P values <0.005 were considered significant. Results: hMLH1 immunoexpression showed decreasing indexes from lesions with lower degrees of dysplasia to lesions with more severe dysplasia. Statistical difference was found mainly between suprabasal layers and total indexes. Conclusions: hMLH1 immunoexpression was inversely related to the OL degree of dysplasia. The total epithelial hMLH1 index seems to be of more clinical relevance than the evaluation stratified by layers. Our findings also suggest a role of such alterations in this pathway of DNA repair as an early event in oral carcinogenesis.     

Clinical usefulness of telomerase activation and telomere length in head and neck cancer

BACKGROUND: Telomere shortening at every replication cycle is postulated to limit the life span of human somatic cells. In contrast, activation of telomerase is proposed to be an essential step for cancer cell immortalization. Head and neck cancer is the most common malignancy in the Indian population compared with Western countries. However, there are very few reports on telomerase activity and telomere length in head and neck cancer. METHODS: Telomerase activation and telomere length alterations were studied in tumor and adjacent normal tissues in 110 patients with head and neck cancer and 40 patients with precancerous/benign conditions. Telomerase activity and telomere lengths were determined by Telomeric Repeat Amplification Protocol (TRAP assay) and Southern blot analysis, respectively. RESULTS: Telomerase activation was observed in 78.2% of the malignant tissues, 85% of the precancerous tissues, and 53.1% of the adjacent normal tissues. Peak terminal restriction fragment length (TRF) was observed to be significantly lower in malignant tissues compared with the adjacent normal tissues. No significant correlation could be observed between telomerase activation and clinicopathologic characteristics of the patients. Two-year disease-free survival analysis showed that patients showing telomerase activation in the adjacent normal tissues and patients showing higher telomere length in malignant tissues had poor disease-free survival. CONCLUSIONS: Our results demonstrate the significant clinical usefulness of telomerase activation and telomere length for head and neck cancer patients. These markers may be helpful in predicting the clinical course of the disease and thus in identifying the patients in need of a close follow-up and vigorous adjuvant treatment.     

纤维喉镜下微波治疗声带白斑25例疗效观察

目的探讨微波治疗声带白斑的疗效。方法对25例声带白斑患者通过纤维喉镜用微波多点热凝治疗声带白斑。结果术后两周,全部患者声音嘶哑均较术前好转。随访1~5年,其中14例单纯性白斑,伴有轻度不典型增生5例均未发生癌变,而伴有中、重度不典型增生者有3例发生癌变。结论纤维喉镜下应用微波治疗声带白斑,具有操作简便,术野清晰,组织损伤小,患者痛苦小,能取得较好的治疗效果。     

Integrin expression in oral hairy leukoplakia and normal tongue epithelium

OBJECTIVE: To describe the expression of integrins in the epithelium of oral hairy leukoplakia (HL) and compare to that of normal lateral tongue epithelium. MATERIALS AND METHODS: Immunohistochemistry to identify integrins (alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1) was performed, using a standard biotin-streptavidin-peroxidase technique on five clinically and histologically confirmed frozen biopsy specimens of HL and five normal lateral tongue control tissues. RESULTS: Expression of integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 was seen both in HL epithelium and in normal control tissue. alpha 5 expression was not seen in HL or in control tissue epithelium. alpha 2 and alpha 3 were expressed mainly in the basal and suprabasal layers; alpha 6 expression was most intense on the basal surface of the basal cells, alpha v was expressed in the basal and suprabasal layers with more expression seen in the higher differentiated cell layers than the other integrins. beta 1 expression was seen in the basal and suprabasal layers only. No apparent difference between HL and normal oral mucosa was noted in the staining pattern of the various integrins. CONCLUSION: Integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 are expressed in HL and the expression pattern is not different from that of normal oral mucosa. alpha 5 is not expressed in HL or in normal oral epithelium.     

Comparison of cytokeratin, filaggrin and involucrin profiles in oral leukoplakias and squamous carcinomas

As the distribution pattern of cytokeratin (CK), filaggrin and involucrin has recently been suggested to discriminate between benign and malignant epithelial growths, biopsies of healthy oral mucosa, leukoplakias without and with dysplasia and squamous cell carcinomas were examined immunohistochemically using a panel of 4 monoclonal antibodies (AB) against different cytokeratin polypeptides (34 beta E12, KL1 and Pkk1) and filaggrin as well as a polyclonal AB to involucrin. Major and statistically significant differences were observed in the profiles of CKs (except Pkk1), filaggrin and involucrin between leukoplakias without and with epithelial dysplasia. However, the alteration in the expression of CKs, filaggrin and involucrin proved to be not a constant feature in leukoplakias with dysplasia as a considerable portion (20-25%) of them revealed the profiles of CKs, filaggrin and involucrin similar to those of benign leukoplakias, and vice versa. Immunostaining of these antigens did not define the diagnosis of dysplasia in leukoplakias more precisely than grading in conventional histology can do so far. However, immunohistochemical sensitivity in detecting a broad range of variation in the abnormal maturation patterns of keratinocytes in leukoplakias with dysplasia can be used to divide these lesions into subgroups to elucidate their prognosis in follow-up studies.     

Risk factors for multiple oral premalignant lesions

Oral leukoplakia, oral submucous fibrosis and erythroplakia are 3 major types of oral premalignant lesions. Multiple oral premalignant lesions may possibly develop due to field cancerization, where carcinogenic exposures can cause simultaneous genetic defects to the upper aerodigestive tract epithelium, putting the epithelium at high risk for development of premalignant lesions at different stages of carcinogenesis. There have been no epidemiological studies on risk or protective factors of the disease. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. A total of 115 subjects with multiple oral premalignant lesions (8-10% of oral premalignant lesions in our case series) were included: 64 subjects with oral leukoplakia and oral submucous fibrosis, 19 subjects with oral leukoplakia and erythroplakia, 22 subjects with oral submucous fibrosis and erythroplakia and 10 subjects with all 3 lesions. Individuals without oral lesions were considered controls (n=47,773). The odds ratio (OR) for ever tobacco chewers was 37.8 (95% confidence interval (CI)=16.2-88.1) when adjusted for age, sex, education, BMI, smoking, drinking and fruit/vegetable intake. Dose-response relationships were seen for the frequency (p<0.0001) and duration of tobacco chewing (p<0.0001) with the risk of multiple oral premalignant lesions. Whereas alcohol drinking may possibly be a risk factor for multiple oral premalignant lesions, smoking was not associated with the risk of multiple oral premalignant lesions (OR=0.9, 95%CI=0.5-1.7). The results suggest that tobacco chewing was the most important risk factor for multiple oral premalignant lesions and may be a major source of field cancerization on the oral epithelium in the Indian population.