Shinsuke Izumaru

Laryngeal solitary multiple mucosal neuromas without multiple endocrine neoplasia (MEN) type 2B

The first case of laryngeal solitary multiple mucosal neuromas (MMN) was reported. A 73-year-old man who had complained of hoarseness and abnormal prickly sensation in the throat for 3 months visited our hospital. Many small whitish-yellow nodules were observed in the laryngeal mucosa from the right arytenoid to the interarytenoid region. Using laryngomicroscopy biopsy was performed twice. The pathological study showed neurogenic nodular lesions consisting of regularly arranged nerve bundles with many axons and Schwann cell proliferation, and so MMN was finally diagnosed. As MMN is regarded as a constant component of multiple endocrine neoplasia (MEN) type 2B, screening of MEN type 2B was performed, however, they were all within normal limits. This case was, therefore, diagnosed as a laryngeal solitary MMN without MEN type 2B.

Cultured stellate cells in human vocal fold mucosa

OBJECTIVES Stellate cells in the maculae flavae, located at both ends of the human vocal fold mucosa, have been considered an independent category of cells. We aimed to isolate and subculture these stellate cells, and to observe their morphological characteristics. METHODS Stellate cells from the maculae flavae and fibroblasts from Reinkes space were cultured in three normal, adult human vocal fold mucosa preparations. RESULTS The subcultured cells from Reinkes space were conventional fibroblasts. The subcultured cells from the maculae flavae were stellate in shape and had cytoplasmic processes. They were larger than conventional fibroblasts, and lipid droplets in the cytoplasm disappeared in the second culture. These stellate cells proliferated by attaching their cytoplasmic processes to each other. During the seven to 10 month subculture period, each cell type continued to exhibit its own morphological characteristics. CONCLUSION This study demonstrated that such stellate cells form an independent cell category, which should be considered as a new category of cells within the human vocal fold.

The immunohistochemical expression of p21WAF1/Cip1 and Proliferating cell nuclear antigen in laryngeal squamous cell carcinomas.

The purpose of this study was to assess the significance of the expression of p21WAF1/Cip1 and proliferating cell nuclear antigen (PCNA) in human laryngeal squamous cell carcinomas. Forty-eight patients (25 supraglottic, 23 glottic) who had undergone operations between 1998 and 2003 were included in this study. The Envision immunohistochemistry method was utilized to stain these tissue specimens. The results showed that the immunostaining of p21WAF1/Cip1 do not show any correlation with differentiation, N stage, metastasis, survival, recurrence or the laryngeal site of involvement. A significant inverse correlation was detected between p21WAF1/Cip1 and the T stage. In contrast, the percentage of PCNA labelled cells showed a significant correlation with the T stage, but not with other clinicopathological parameters. There were differences in the expression of p21WAF1/Cip1 and PCNA between the supraglottic and the glottic carcinomas. In conclusion, our findings suggest that p21WAF1/Cip1 and PCNA may play an important role in the progression of carcinoma of the supraglottic larynx.

R072: Down-Regulation of p21Waf-1 Protein in Laryngeal Carcinoma

PROBLEM: Apoptosis induced by DNA damages is a basic mechanism in exposure to radiation or chemotherapeutic agents in the treatment of carcinomas. The team analyzed the relation between p21Waf-1 protein and ionizing radiation (IR)induced apoptosis in human squamous cell carcinoma. METHODS: Apoptosis was induced by IRor UV in human laryngeal carcinoma (HEp-2) and uterine cervical carcinoma (HeLa) cells. In both cell lines, over-expression of p21Waf-1 protein was observed by transient transfection and in a tetracycline-regulated system, whereas suppression of p21Waf-1 protein was observed by using antisense oligodeoxynucleotide transfection. Immunohistochemical analysis of carcinomas from patients with recurrence after the radiotherapy was also done. RESULTS: IR steadily induced p21Waf-1 protein in HEp-2 cells, but not in HeLa cells. In contrast, p53 protein was induced in a similar manner after IR or UV treatment. UV caused rapid, dramatic and caspase-independent reduction of p21Waf-1 protein in both cancer cells. Only in HEp-2 cells, p21Waf-1 protein recovered close to the basal level. Furthermore, over-expression of p21Waf-1 protein rescued IRand UV-induced apoptosis by transient transfection. As a result, suppression of p21Waf-1 protein caused by antisense oligodeoxynucleotide transfection facilitated UV-induced apoptosis in both HEp-2 and HeLa cells. There were expressions of p53 and p21 in human laryngeal carcinomas. CONCLUSION: P21Waf-1 protein (modified independently from p53) functions as an inhibitor of IRas well as UVinduced apoptosis in squamous carcinoma cells; p53 and p21 may play important roles in the progression of LSCC. SIGNIFICANCE: P53 and p21 may play important roles in the progression of LSCC.