Yasuto Yoshihama

Expression of vascular endothelial growth factor-C predicts regional lymph node metastasis in early oral squamous cell carcinoma.

The purpose of this study was to investigate the association of the expression of vascular endothelial growth factor-C (VEGF-C) with regional lymph node metastasis in oral squamous cell carcinoma (OSCC). The expression of VEGF-C in biopsy specimens obtained from 62 patients with OSCC was examined by immunohistochemistry. In the early stages of T1 and T2 (38 cases), VEGF-C expression strongly correlated with lymph node metastasis (P < 0.001), and the percentage of VEGF-C-positive staining was 88.2% for patients with lymph node metastasis (15 of 17 cases) and 28.6% for those without lymph node metastasis (6 of 21 cases). However, in the advanced stages of T3 and T4, no significant correlation between VEGF-C expression and lymph node metastasis was observed. These results indicate that VEGF-C expression in biopsy specimens can be used as a reliable predictor of regional lymph node metastasis, particularly in early OSCC, and may become an important factor in the selection of appropriate treatment.

Prognostic significance of ERRB3 overexpression in oral squamous cell carcinoma

Immunohistochemical analysis of erbB3, as the third member of epidermal growth factor receptor gene family, was performed on 41 cases of oral squamous cell carcinoma, correlating the staining pattern with clinical outcome. High expression of erbB3 protein (ERBB3) was significantly associated with lymph node metastasis (P < 0.05), survival rate (P < 0.05) and mode of invasion (P < 0.01) in this series. These results demonstrated that ERBB3 expression may be helpful in identifying those oral squamous cell carcinomas with higher malignant potential.

p53 and MDM2 Expression in Oral Squamous Cell Carcinoma

The p53 tumor suppressor gene is the most commonly mutated gene in human cancer and is a frequent abnormality in oral squamous cell carcinoma and its precancerous lesions. MDM2 (murine double minute-2), a new proto-oncogene, may be associated with p53 gene products and may negatively affect the transcriptional activating function of p53. The purpose of this study was to investigate the incidence of MDM2 and its relationship to the expression of p53 in oral squamous cell carcinoma and precancerous lesions. Overexpression of p53 and MDM2 proteins was detected in 52 and 40% of oral squamous cell carcinomas, respectively. p53 gene mutation, absent in normal oral epithelium was observed in 31% of the carcinoma cases. Our finding suggested that MDM2 protein may be an alternative mechanism causing p53 protein dysfunction in oral squamous cell carcinoma.

Identification of CCDC62-2 as a novel cancer/testis antigen and its immunogenicity

Cancer/testis (CT) antigens are expressed in normal germ line tissues and various cancers. They are considered promising target molecules for immunotherapy for patients with various cancers. To identify CT antigens, we performed serological identification of antigens by recombinant expression cloning. The humoral immune response of cancer patients against a newly defined antigen was analyzed. A testicular cDNA library was immunoscreened with serum obtained from a gastric adenocarcinoma patient whose primary cancer had regressed once and most liver metastasies had disappeared transiently. We isolated 55 positive cDNA clones comprising 23 different genes. They included 4 genes with testis‐specific expression profiles in the Unigene database, including coiled‐coil domain containing 62 (CCDC62). RT‐PCR analysis showed that the expression of 2 splice variants of CCDC62 was restricted to the testis in normal adult tissues. In malignant tissues, CCDC62 variant 2 (CCDC62‐2) was aberrantly expressed in a variety of cancers, including stomach cancer. A serological survey of 191 cancer patients with a range of different cancers by ELISA revealed antibodies to CCDC62‐2 in 13 patients, including stomach cancer. None of the 41 healthy donor serum samples were reactive in the same test. The serum reaction against CCDC62‐2 was confirmed by western blot. CCDC62‐2 is a CT antigen that is immunogenic in cancer patients.

Apoptosis and p53 are associated with effect of preoperative radiation in oral squamous cell carcinomas.

This study was carried out to elucidate whether apoptosis and p53 can be used to stratify oral cancer patients into groups with a favorable or unfavorable response to preoperative radiation therapy. Thirty-two patients were evaluated. The apoptosis index was 1.7+/-0. 9% in the ineffective cases, and it was significantly lower than effective cases (3.2+/-1.2%). While 14 of 16 effective cases (86.7%) did not express p53, 13 of 16 ineffective cases (81.3%) overexpressed p53. These results suggest that mutated p53 in tumors is associated with a poor response to radiation which may be related to evasion of apoptosis in oral cancer.

Interleukin-1 beta in unstimulated whole saliva is a potential biomarker for oral squamous cell carcinoma

The objective of this study was to evaluate cytokines in unstimulated whole saliva (UWS) of oral squamous cell carcinoma (OSCC) patients as compared to those with pre- and post-operation for evaluation as markers of OSCC. Sixteen OSCC patients were included in this study. Cytokine concentrations in resting saliva were measured using a Bio-Plex suspension array system. Only interleukin-1 (IL-1) beta showed significantly different cytokine concentration in saliva between pre- and post-operation. IL-1 beta was released from cultured OSCC cells confirmed by ELISA and immunohistochemistry. From this study, IL-1 beta in UWS may be useful for detection of early stage OSCC. More studies are needed to accept the utility of IL-1 beta in UWS for predicting, diagnosis and evaluation of OSCC.

Tumor protein D54 is a negative regulator of extracellular matrix-dependent migration and attachment in oral squamous cell carcinoma-derived cell lines

PurposeTumor protein D54 (TPD54) belongs to the TPD52 family of proteins and is expressed in several types of cancer, including oral squamous cell carcinoma (OSCC). Here, we investigated relationships between various OSCC-related characteristics and TPD54 expression in vitro.MethodsThe expression of TPD54 in several OSCC-derived cell lines and normal, non-malignant, cells was assessed. Based on the results obtained, OSCC-derived SAS cells were subsequently subjected to exogenous over-expression of alternative splice variants (ASVs) of TPD54 and to TPD54 knock-down, mediated by siRNA. Next, the role of TPD54 in cellular growth, apoptosis, invasion, migration and extracellular-matrix (ECM)-dependent migration and attachment was investigated, as also the concomitant expression of integrins and integrin-related proteins by the OSCC-derived cells.ResultsWestern blot analysis and RT-PCR revealed that several TPD54 ASVs were expressed in the OSCC-derived cell lines tested. Neither exogenous ASV over-expression nor TPD54 knock-down modulated the proliferation or invasion of SAS cells in a monolayer culture assay. However, exogenous ASV over-expression did decrease anchorage-independent growth and TPD54 knock-down did increase anchorage-independent growth, irrespective of caspase activities. The same effects were observed on ECM-dependent cellular migration and cell attachment to the ECM. The expression levels of the major α and β integrin subunits, and of E-cadherin, were found to be similar to those observed in the non-transfected control cells, whereas talin1 expression was found to be increased after TPD54 knock-down. Also Akt was found to be activated after TPD54 knock-down, even in the absence of serum stimulation. Very similar effects were observed in the OSCC-derived cell lines HSC 2 and HSC 3.ConclusionsOur results show that TPD54 affects OSCC cell attachment to the ECM, OSCC cell migration, and Akt/PKB activation by modulating integrin activation via a talin1-mediated inside-out signal of the ECM. Based on these results, we suggest that TPD54 may serve as a novel biomarker for OSCC and as a putative target for OSCC therapy.

Clinico-statistical analysis of mucoepidermoid carcinoma.

1982年4月より1999年3月までに岡山大学歯学部附属病院第二口腔外科を受診し, 病理組織学的に粘表皮癌と診断された27例について臨床統計的検討を行ったので報告する。 (1) 性別発生頻度は, 男性16例, 女性11例。 (2) 年齢別発生頻度は平均63.0歳であった。 (3) 部位別発生頻度をみると大唾液腺2例, 小唾液腺25例。 (4) TNM分類ではT1が7例, T2が7例, T4が13例であり, Stage別では, Stage Iが7例, Stage IIが7例, Stage IVが13例であった。 (5) 治療法については, 24例に対して外科療法を施行し, そのうち外科療法の単独施行は13例, 化学療法および放射線療法の併用療法を施行したものは11例であった。 (6) 全体の5年累積生存率は69.4%で, Stage I, II症例が90.9%, Stage IV症例が46.4%であった。