Kazunori Kidani

High expression of EZH2 is associated with tumor proliferation and prognosis in human oral squamous cell carcinomas

Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb group of genes and is important in cell cycle regulation. Overexpression of EZH2 protein has been associated with biological malignancy of prostate cancer and several other cancers. The aim of the present study was to evaluate the expression of EZH2 protein in human oral normal mucosa, dysplasia and oral squamous cell carcinoma (OSCC) with clinicopathological profiles. EZH2 expression was assessed by Western blotting and immunohistochemistry in 3 OSCC cell lines, 10 normal mucosae, 50 dysplasias and 102 OSCCs. The labeling indices (LIs) of EZH2, Ki-67, P53, and the apoptotic index (AI) were evaluated by immunohistochemistry and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) method. Western blot analysis detected EZH2 protein as a single band at 91kDa in the 3 OSCC cell lines, but it was almost absent in non-tumoral oral mucosae. The LI of EZH2 was highest in the OSCCs, followed by the dysplasias (p<0.05) and normal mucosae (p<0.05) with significant difference. The LI of EZH2 correlated with the clinical stage, tumor size, lymph node metastasis and LIs of Ki-67 and P53, but not with the AI in OSCCs, and inversely correlated with the histological differentiation of OSCCs. The survival rate calculated by the Kaplan-Meier method revealed that OSCC patients with higher EZH2 expression showed poorer prognosis than those with a lower EZH2 expression (p<0.01). These results suggest that overexpression of EZH2 is correlated with malignant potential and poor prognosis in OSCCs. EZH2 might serve as a novel biomarker for predicting prognosis in patients with OSCCs.

CYR61 downregulation correlates with tumor progression by promoting MMP-7 expression in human gastric carcinoma.

Objective: CYR61 (cysteine-rich 61) belongs to the CCN (CYR61/CTGF/NOV) protein family and is involved in tumorigenesis. We have previously confirmed that the level of CYR61 protein is decreased in gastric carcinoma compared with nontumoral mucosa, by conducting proteome-based analyses. In this study, we examine the relationship between CYR61 expression and clinicopathological data of MMP-7 expression in human gastric mucosae and tumors. Methods: Immunohistochemical and/or immunofluorescence analyses were performed to examine the histological expression of CYR61 in normal gastric mucosa, intestinal metaplasia, 33 adenomas, and 127 carcinomas. Seven gastric carcinoma cell lines were used to examine the expression of CYR61 and MMP-7 by Western blotting. Results: The CYR61-expressing cells mostly coincided with the serotonin-containing cells, not only in nontumoral epithelia, but also among tumor cells. CYR61 expression was positive (labeling index: >2%) in 43 of 49 early gastric carcinomas (87.8%) and in 19 of 78 advanced gastric carcinomas (24.4%), the frequency being significantly lower in the latter (p < 0.001). All the normal mucosae, intestinal metaplasias and adenomas were in the positive group. The reduction in CYR61 expression correlated significantly with histological differentiation (p < 0.05), depth of invasion (p < 0.001), lymphatic invasion (p < 0.001), venous invasion (p < 0.001), lymph node metastasis (p < 0.001) and clinical stage (p < 0.001). Immunohistochemistry and Western blotting revealed the expression of CYR61 to be inversely correlated with that of MMP-7 (p < 0.001). Conclusions: CYR61 is expressed in serotonin-containing cells, and downregulation of the expression might contribute to the progression of cancer by promoting MMP-7 expression in human gastric carcinomas.

High expression of enhancer of zeste homologue 2 indicates poor prognosis in patients with soft tissue sarcomas.

Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group of genes, is associated with malignancy in several human cancers. The purpose of this study was to examine the association between EZH2 expression and clinicopathological factors as compared to Ki-67 expression in human soft tissue sarcomas. Expression of EZH2 and Ki-67 was immunohistochemically determined in paraffin-embedded sections from 104 soft tissue sarcomas. High expression of both EZH2 and Ki-67 was significantly correlated with distant metastasis (P<0.01), histologic grade (P<0.01) and poor prognosis (P<0.01), but not with clinicopathological factors such as age, sex, and tumor location and size. Although EZH2 expression was significantly correlated with Ki-67 expression (rs=0.65, P<0.01), multivariate analysis showed that high expression of EZH2, but not of Ki-67, was an independent factor of poor prognosis (relative risk = 2.79; P=0.02). These data suggest that expression of EZH2 is a novel and reliable prognostic marker of human soft tissue sarcomas.

A Case of Actinomycosis of the Minor Salivary Gland in the Buccal Region

Abstract We report a case of actinomycosis arising in the minor salivary gland in the buccal region. A 71-year-old male presented with a swelling in the left buccal region. The clinical diagnosis was minor salivary gland tumor in the buccal mucosa. Under local anesthesia, the lesion was excised. Histopathological examination showed basophilic amorphous masses of Actinomyces in the dilated excretory duct with squamous metaplasia. A final diagnosis of actinomycosis was made. Its portal of entry was thought to be a disruption of the mucosal barrier after trauma due to maladaptation of dentures. There was no sign of recurrence after the surgery.

A Case of Rheumatoid Nodules of the Buccal Region

We present the case of rheumatoid nodules in the buccal region, in a 78-year-old female patient with rheumatoid arthritis, who presented with swelling of the left buccal region. Resection was performed under general anesthesia and revealed a mass that was a collection of nodules. The pathological diagnosis was rheumatoid nodules which had a central area of necrosis surrounded by palisades of histiocytes. To date, there has been no evidence of disease recurrence.