MicroRNA‐137 promoter methylation in oral lichen planus and oral squamous cell carcinoma

Oral lichen planus (OLP) is a common oral mucosal disease, which is generally considered a potentially malignant lesion. To identify efficiently prognostic biomarker, we investigated the microRNA‐137 (miR‐137) promoter methylation in OLP and compared with the samples from healthy volunteers and patients with oral squamous cell carcinoma (OSCC). A total of 20 OLP and 12 patients with OSCC as well as 10 healthy subjects were subjected to miR‐137 promoter methylation analysis using methylation‐specific PCR (MSP). To address the malignancy prediction potential from miR‐137 promoter methylation status, methylation of the p16 gene, a well‐known tumor suppressor, was investigated in the same samples. The p16 methylation and miR‐137 promoter methylation were found to be 25% and 35% in patients with OLP, 50% and 58.3% in patients with OSCC, and 0% and 0% in healthy subjects, respectively. The differences between miR‐137 and p16 methylation levels were statistically significant between healthy controls and patients. Methylation levels of the two promoters were also influenced by age, gender, and lesion duration. Interestingly, aberrant promoter methylation of the p16 and miR‐137 genes was only found in the epithelium but not in the connective tissue from patients with OLP. This raises the possibility to use miR‐137 methylation as a biomarker for malignant prediction in patients with OLP.     

Lack of evidence for prognostic value of epidermal growth factor receptor intron‐1 CA repeats for oral carcinomas

Epidermal growth factor receptor (EGFR) expression is altered in several malignancies, including oral squamous cell carcinoma. A CA‐repeat polymorphism in intron‐1 (CA‐SSR‐1) of the EGFR gene is reported to influence EGFR expression and is associated with features of various solid tumors and outcomes of cancer patients. In the present study we evaluated the influence of length and zygosity of CA‐SSR‐1 on the survival of patients with oral squamous cell carcinoma. The length and zygosity of CA‐SSR‐1 was obtained through microsatellite analysis in 91 patients with oral cancer, who were treated in the Department of Oral and Maxillofacial Surgery of the University Medical Centre Hamburg Eppendorf, Germany, during the years 1998–2008. Follow up was conducted until 2016. Outcome measures were age, gender, tumor stage, occurrence of metastases, and date of recurrence or death. Statistical analysis was conducted using the chi‐square test and the log‐rank test. Neither length nor zygosity of the CA‐SSR‐1 in patients with oral squamous cell carcinoma was significantly correlated with sex, age, tumor size, tumor localization, lymph node involvement, metastasis status, disease‐free survival, or overall survival. Length and zygosity of the CA‐SSR‐1 polymorphism in EGFR is not able to serve as a prognostic biomarker in White European patients with oral squamous cell carcinoma.     

Co‐expression of Hif1α and CAIX is associated with poor prognosis in oral squamous cell carcinoma patients

J Oral Pathol Med (2010) 39 : 313–317 Background: This study investigates the prognostic impact of the expression of hypoxia‐inducible factor 1α (Hif1α) and carbonic anhydrase IX (CAIX) detected by immunohistochemistry in oral squamous cell carcinoma (OSCC). Methods: Statistical analysis of immunohistochemical results with clinical parameters including survival outcomes was performed for 80 OSCC patients. Results: Patients with a low expression of both proteins survived on average 54.8 months, whereas those with an increased expression of Hif1α in their tumors combined with a low expression of CAIX survived on average only 37.6 months (P = 0.026). In multivariate Cox’s regression hazard analysis, again patients with a low expression of Hif1α/CAIX had the best prognosis, whereas patients with increased Hif1α and low CAIX expression carried a 4.97‐fold increased risk of tumor‐related death (P = 0.042). Conclusion: A co‐detection of low Hif1α/CAIX expression is significantly correlated with a better prognosis for OSCC patients, which may have implications for therapy options for these patients.     

PI3K与PTEN蛋白在口腔鳞癌中的表达及相关性研究

目的：探讨口腔鳞癌中PTEN、PI3K的表达情况,并对其表达水平与临床特征之间的关系进行相关性分析,探讨其与口腔鳞癌发生、发展和转移的关系。方法采用免疫组化SP法对52例口腔鳞癌石蜡标本及20例癌旁正常组织中PTEN、PI3K蛋白的表达情况进行研究,分析其与临床病理特征的关系。结果 PTEN在口腔鳞癌中表达明显低于癌旁正常组织。PI3K表达明显高于癌旁正常组织。PTEN与PI3K表达与细胞分化、临床分期、淋巴结转移相关。PTEN与PI3K阳性表达之间呈负相关。结论 PI3K在口腔鳞癌中的表达上调, PTEN在口腔鳞癌中的表达下调。PTEN与PI3K蛋白表达呈负相关。     

Chemotherapy‐induced oral mucositis and associated infections in a novel organotypic model

Oral mucositis is a common side effect of cancer chemotherapy, with significant adverse impact on the delivery of anti‐neoplastic treatment. There is a lack of consensus regarding the role of oral commensal microorganisms in the initiation or progression of mucositis because relevant experimental models are non‐existent. The goal of this study was to develop an in vitro mucosal injury model that mimics chemotherapy‐induced mucositis, where the effect of oral commensals can be studied. A novel organotypic model of chemotherapy‐induced mucositis was developed based on a human oral epithelial cell line and a fibroblast‐embedded collagen matrix. Treatment of organotypic constructs with 5‐fluorouracil (5‐FU) reproduced major histopathologic characteristics of oral mucositis, such as DNA synthesis inhibition, apoptosis and cytoplasmic vacuolation, without compromising the three‐dimensional structure of the multilayer organotypic mucosa. Although structural integrity of the model was preserved, 5‐FU treatment resulted in a widening of epithelial intercellular spaces, characterized by E‐cadherin dissolution from adherens junctions. In a neutrophil transmigration assay we discovered that this treatment facilitated transport of neutrophils through epithelial layers. Moreover, 5‐FU treatment stimulated key proinflammatory cytokines that are associated with the pathogenesis of oral mucositis. 5‐FU treatment of mucosal constructs did not significantly affect fungal or bacterial biofilm growth under the conditions tested in this study; however, it exacerbated the inflammatory response to certain bacterial and fungal commensals. These findings suggest that commensals may play a role in the pathogenesis of oral mucositis by amplifying the proinflammatory signals to mucosa that is injured by cytotoxic chemotherapy.