Overexpression of Platelet-Derived Growth Factor and Its Receptor Are Correlated with Oral Tumorigenesis and Poor Prognosis in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a cancerous disease with poor prognosis. According to the statistics, the 5-year survival rate has not improved significantly over the past 20 years. The platelet-derived growth factor (PDGF) and its signaling pathway is a key regulator of angiogenesis and tumorigenesis. High level of PDGF and its receptor (PDGFR) have been reported in several types of malignancies. In this study, we investigated the relationship of the molecular expression levels of PDGF and PDGFR with clinicopathological parameters in OSCC. To this end, we measured the mRNA and protein levels of PDGF and PDGFR by real-time quantitative PCR (qRT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA), respectively. We found positive correlations of the mRNA levels of PDGFA, PDGFB, and PDGFRB with lymph node metastasis and poor overall survival (OS). High expression of PDGF, PDGFRA, and PDGFRB were remarkably associated with lymph node metastasis and poor OS, as determined by immunohistochemistry. Preoperative serum levels of PDGF-AA and PDGF-BB had a positive correlation with preoperative platelet count. Elevated serum levels of PDGF-AA. PDGF-BB, and platelet count correlated with lymph node metastasis and an unfavorable outcome. In multivariate Cox regression analysis, PDGFA mRNA, PDGFB mRNA, PDGFRB mRNA, PDGF immunoexpression, PDGFRB immunoexpression, serum PDGF-AA, serum PDGF-BB, and platelet count emerged as significant independent prognostic factors for OS. In vitro, we found that elevated PDGF promotes colony formation, migration, and invasiveness of SAS and OECM-1 cancer cell lines. Our results suggest that the expression level of serum PDGF has the potential to become a useful diagnostic marker for the prognosis of OSCC. In addition, PDGFR should be considered as a potential therapeutic target for OSCC. Furthermore, research should be undertaken to elucidate the role of PDGF and PDGFR regarding the behavior of tumor cells in OSCC.

Plasma miR-187* is a potential biomarker for oral carcinoma.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is prevalent worldwide, and survival in OSCC has not improved significantly in the past decades. MicroRNAs (miRNAs) have an important regulatory role in oral carcinogenesis. This study investigated the functional and clinical implications of miR-187* in OSCC pathogenesis. MATERIALS AND METHODS: Expression of miR-187* in OSCC tissues and patient plasma was assayed using quantitative RT-PCR. The diagnostic power was specified using receiver operator curve analysis. The phenotypic influence of miR-187* in OSCC cells was delineated using exogenous expression. RESULTS: miR-187* was upregulated in OSCC tissue relative to control mucosa. Overexpression of miR-187* enhanced the oncogenic phenotype of OSCC cells, including cell migration and anchorage-independent colony formation. Plasma miR-187* levels could be used to distinguish patients from controls with a separating power of 0.73. Patients showing a reduction in plasma miR-187* after tumor resection had a better prognosis. CONCLUSION: miR-187* plays oncogenic roles in oral carcinogenesis. Plasma miR-187* could be validated as a marker of OSCC for diagnostic uses. CLINICAL RELEVANCE: This research implied that plasma miR-187* was a diagnostic marker for patients with OSCC, and plasma miR-187* level could be a prognostic factor for OSCC patients who received ablation surgery.

Mucosa-associated lymphoid tissue lymphoma at the parotid gland.

MALT (mucosa-associated lymphoid tissue) lymphomas are low-grade extra-nodal B-cell lymphomas that may involve various sites in the head and neck including the thyroid, salivary, and lacrimal glands. Development of MALT lymphoma in the head and neck is often associated with auto-immune diseases such as Sjögren syndrome or Hashimoto thyroiditis. Here, we report a case of a MALT lymphoma of the left buucal mucosa that likely arose in the parotid gland. The patient was successfully treated with surgical excision with chemotherapy and remained disease-free at the 10-year follow-up. Since it was rare in the head and neck region, we present this case.

Application of in vivo stain of methylene blue as a diagnostic aid in the early detection and screening of oral squamous cell carcinoma and precancer lesions.

BACKGROUND: Early detection of oral malignant or precancerous lesion by screening individuals with high-risk factors may identify candidates who should receive treatment to prevent cancer progression and reduce patient mortality. Among the diagnostic tools, in vivo staining is advocated as a simple, inexpensive, and fairly sensitive method. METHODS: The present study involved the examination of 58 patients suspected of having oral malignant or precancerous lesions by methylene blue staining. The results of methylene blue uptake were compared with a simultaneous biopsy of these lesions. The pathologically confirmed precancers and cancers were the positive targets of this screening, while benign epithelial lesions were sorted as negative subjects of screening. RESULTS: The results revealed sensitivity of 90%, specificity of 69%, positive predictive value of 74%, and negative predictive value of 87%. CONCLUSION: We consider that methylene blue staining is a useful diagnostic adjunct in a large, community-based oral cancer screening program for high-risk individuals.

Use of methylene blue as a diagnostic aid in early detection of oral cancer and precancerous lesions.

We assessed the sensitivity, specificity, and positive and negative predictive value of methylene blue staining in the diagnosis of oral cancer in 58 patients. The sensitivity was 90%, the specificity 69%, positive predictive value 74%, and negative predictive value 87%. Because of the number of false negatives and false positives we recommend that the diagnosis should always be confirmed by histopathological examination of a biopsy specimen. Methylene blue staining may, however, be useful as a screening tool for oral cancer in large, high-risk groups in a similar way to the more expensive toluidine blue.

MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder.

OBJECTIVES: MicroRNAs (miRNAs, miRs) have shown diagnostic and prognostic potential for oral cancer but their role in oral potentially malignant disorder (OPMD) has been less investigated. We aimed to assess whether miR-21 and miR-31, two of the most relevant miRNAs in oral cancer, are useful as prognostic factors for OPMD progression. MATERIALS AND METHODS: miR-21 and miR-31 in 20 saliva samples and 46 tissue samples from patients with OPMD (mean follow-up of 820days) were analyzed by quantitative reverse transcription PCR and in situ hybridization, respectively. The log-rank test, receiver operating characteristic curve, and Kaplan-Meier disease free survival analysis were used to assess the correlation between miRNA levels and OPMD progression. RESULTS: Significantly increased salivary miR-21 and miR-31 expression (P=0.003 and P<0.001, respectively) was observed in patients with OPMD compared to control individuals. Patients with recurrent OPMD and/or malignant transformation exhibited a further augmented expression of miR-31, but not miR-21, in the epithelium. Furthermore, increased miR-31 expression as well as epithelial dysplasia is an independent risk factor for OPMD progression as demonstrated in Cox-proportional hazard model (HR: 8.43, P<0.05, 95%CI: 1.04 to 68.03). CONCLUSIONS: Salivary miR-21 and miR-31 are applicable as useful OPMD screening tools. Epithelial dysplasia and miR-31 up-regulation synergistically predict the increased incidence of recurrence and/or malignant transformation in patients with OPMD. Detection of miR-31 expression is an adjuvant method for screening of high-risk OPMD.

EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.

BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGFR) are part of an important signaling pathway that is involved in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that EGF/EGFR genetic polymorphisms might have a prognostic impact on disease-free survival and overall survival (OS) in locally advanced SCCHN. MATERIALS AND METHODS: The patient group included a consecutive cohort of 180 patients with locally advanced SCCHN who underwent postoperative concurrent chemoradiotherapy between 2002 and 2010. DNA from formalin-fixed, paraffin-embedded tumor tissues was genotyped for the single nucleotide polymorphism (SNP) of EGF A61G A>G, EGFR R521K G>A and G-216T. The log-rank test was applied to evaluate the impact of SNPs on the outcomes. Survival was estimated using the Kaplan-Meier statistical method. RESULTS: We demonstrated that EGF/EGFR SNPs might predict prognosis in patients with primary pharyngolaryngeal tumors, but not in those with oral cavity tumors. In pharyngolaryngeal tumor subgroup, EGF61 G/G genotype led to worse 5 year OS rate when compared to G/A or A/A genotypes (13.3% versus 34.3% versus 50.0%, P=0.017). The 5 year OS of patients with EGFR R521K G/G (11.1%) and G/A (15.9%) were lower than the A/A (62.5%) genotype (P=0.054). Patients carrying one or two unfavorable alleles had worse 5 year OS than those without unfavorable allele (not available versus 20% versus 71.4%, P=0.002). Multivariate analysis revealed that the highest risk of death was associated with the coexistence of two unfavorable genotypes (hazard ratio 25.7, 95% confidence interval =3.4-193.4; P=0.002). CONCLUSION: In this study, we were able to demonstrate that the EGF A61G and EGFR R521K genetic polymorphisms might be important prognostic factors in patients with locally advanced primary pharyngolaryngeal squamous cell carcinoma who underwent postoperative concurrent chemoradiotherapy.