A case of extranodal NK/T-cell lymphoma, nasal type, diagnosed by scraping cytology of the maxillary gingiva.

Extranodal NK/T-cell lymphoma (ENKTL), nasal type, is often seen in the head and neck region, but there have been rare instances of this disease with initial presentation as a lesion in the oral mucosa. The patient, a woman in her seventh decade of life, presented with an ulcer in the maxillary gingiva, and scraping cytology and biopsy were performed. Cytological specimens showed solitary or small aggregating cells with marked atypia in a necrotic background. Tumor cells were detected that had various nuclear shapes and azure granules in the cytoplasm. Biopsy showed that the tumor cells had diffusely infiltrated or interdigitated into the subepithelium. Immunohistochemistry revealed that the tumor cells had T- and NK cell phenotypes and were Epstein-Barr virus-encoded small RNA (EBER) positive, leading to a diagnosis of ENKTL. Thus, when nonepithelial tumor cells in a necrotic background and prominent atypia are found, as in this case, it is important to carefully observe for azurophil granules in the cytoplasm for differential diagnosis considerations.

Clinicopathological Significance of the ET Axis in Human Oral Squamous Cell Carcinoma.

The interaction between cancer cells and the surrounding microenvironment in malignant tumor tissue is known to be closely associated with cancer cell invasion and proliferation. Endothelin (ET) present in the microenvironment surrounding tumors has been reported to play a role in cancer cell invasion and proliferation by binding to receptors on the cell membrane of cancer cells. Here, we immunohistologically detected the expression of ET-1 and its receptor ETAR in oral squamous cell carcinoma (OSCC) and evaluated the association between the expression of each as well as their co-expression (ET-axis expression) and clinicopathological factors. A significant difference was observed between the invasion pattern as a parameter of cancer cell malignancy and the expressions of ET-1 and ETAR. The survival rates were significantly lower among the patients who were strongly positive for ET-1 and the ETAR-positive patients compared to negative patients. There was also a significant difference between ET-axis expression and the degree of histological differentiation and mode of invasion, and the survival rate of the positive cases was significantly lower than that of the negative cases. Our findings suggested that ET-axis assessments are important for assessing the malignancy of cancer cells and predicting the prognoses of OSCC patients.

Loss of epidermal growth factor receptor expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition.

Inhibition of epidermal growth factor receptor (EGFR) signaling has emerged as a novel therapeutic strategy for the treatment of oral squamous cell carcinoma (OSCC). The EGFR-directed inhibitor cetuximab is currently the only approved targeted therapy for the treatment of OSCC. EGFR status may affect the patient response to cetuximab treatment. In the present study, via analysis of the immunomarker for EGFR, it was revealed that 58.3% of the total cases investigated stained positively for EGFR expression, and furthermore, that invasiveness was inversely correlated with EGFR expression. Expression levels of EGFR were quantified, and the correlation between EGFR expression and cetuximab sensitivity was investigated using three varying grades of invasive human OSCC line. EGFR expression in high-grade invasive cells was significantly downregulated compared with that of low-grade invasive cells. There was no significant antiproliferative effect in the high-grade invasive cells treated with various concentrations of cetuximab. The EMT-associated genes, N-cadherin, vimentin and Snail, were upregulated in the high-grade invasive cells. The low-grade invasive cells exhibited characteristics of typical epithelial cells, including the expression of E-cadherin and absence of the expression of N-cadherin, vimentin and Snail. Transforming growth factor-ß induced low-grade invasive cells to undergo an epithelial-mesenchymal transition (EMT)-associated gene switch, which resulted in low levels of EGFR expression. The results of the present study suggested that loss of EGFR expression in OSCC was associated with EMT, and may have functional implications with regard to tumor invasiveness and the resistance to cetuximab treatment.

Loss of claudin-7 is a negative prognostic factor for invasion and metastasis in oral squamous cell carcinoma.

Claudin-7 belongs to the claudin family, which consists of 24 subtypes of essential tight junction (TJ) integral membrane proteins with molecular weights of 20-27 kDa. We investigated the interrelationship between clinicopathological findings and claudin-7 expression in oral squamous cell carcinoma (OSCC). Using immunohistochemical techniques to examine the expression levels of claudin-7 in 67 cases of OSCC, claudin-7 expression was detected in 35 (52.2%) of the 67 cases. We also compared the clinicopathological features of the OSCC cases with claudin-7 expression levels. Moreover, six cell lines with various invasive properties were investigated in vitro to compare mRNA and protein levels of claudin-7 using reverse transcription-polymerase chain reaction (RT-PCR) and the western blotting method. Decreased claudin-7 expression correlated significantly with T-category (p<0.05), lymph node metastasis (p<0.01), and mode of invasion (p<0.001). Patients with positive claudin-7 expression had a significantly better prognosis (p<0.05). Claudin-7 protein and mRNA levels were lower in the HOC313 and TSU cells, which have higher invasive potentials compared with other cell lines. These results suggest that loss of claudin-7 expression is associated closely with invasion and lymph metastasis and is an unfavorable prognostic factor in patients with OSCC.