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1 Expression of PCNA and c-erbb- 2 in mucoepidermoid carcinoma of salivary glands: An immunohistochemical study Shigeru YAMABE E Akio MIZUNO E Shuichi FUJITA* Hiroshi TAKAHASHI* E Haruo OKABE* Abstract: In 30 cases of mucoepidermoid carcinoma of the salivary glands, the expressions of proliferating cell nuclear antigen (PCNA) and c-erbb- 2 oncogene products were investigated immunohistochemically. A statistically significant difference was found between solid regions (12.26 }9.95) and tubular regions (0.77 }2.01) on the basis of the PCNA index. Three types of c-erbb- 2 antibodies (NCL-PC11, CB11, and CBE 1) showed different patterns of expression. C-erbB- 2 (PC11) was expressed on the cell membranes of solid regions in 17 cases (57%) and tubular regions in 7 cases (23%). C-erbB- 2 (CB11) was expressed in the cytoplasm of solid regions in 20 cases (67%) and tubular regions in 7 cases (23%). Moreover, c- erbb- 2 (CBE 1) was expressed in tubular regions in only 2 cases (7 %). In the present study, PCNA index was not related to the overexpression of c-erbb- 2 in mucoepidermoid carcinoma. First Department of Oral and Maxillofacial Surgery, Nagasaki University School of Dentistry (Chief: Prof. Akio Mizuno) *Department of Oral Pathology, Nagasaki University School of Dentistry (Chief: Prof. Haruo Okabe)

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3 Vol. 43 No. 10 写 真1粘 唾 液 腺 粘 表 皮 癌 に お け るPCNAお 表 皮 癌HE染 よ びc-erbB-2の 色( 100) 写 真4粘 707 発現 表 皮 癌 の 充 実 部c-erbB-2(NCL- PC11)( 200) 写 真2粘 表 皮 癌 の 充 実 部PCNA( 200) 写 真5粘 表 皮 癌 の 腺 管 部c.erbB-2(NCL- PC11)( 200) よ び 強 陽 性(冊);50%以 もの,4群 上 の 陽性 細 胞 が 認 め られ る に 分 け た. さ らに,c-erbB-2とPCNAの 関連 性 を求 め る た め に,各 構 成 組 織 に 対 して,そ れ ぞ れc-erbB-2(PC11) の 陽 性 度 別(陰 性 群,弱 陽 性 群,中 性 群)にPCNA陽 結 1.各 写 真3粘 PCNA陽 果 抗体 の 陽性 像 1)PCNA陽 表皮 癌 の腺 管 部PCNA( 200) 陽性 群 お よび 強 陽 性 率 を 求 め た. 性像 性 細 胞 は 正 常 唾 液 腺 お よ び 導 管 に お い て, ほ と ん ど認 め ら れ な か っ た.ま た,粘 表 皮 癌 の 充 実 部 NCL-PC11に erbb-2(pc11)の に お い て は,び ま ん 性 に 陽 性 所 見 が み られ,特 お い て は,特 に 詳 細 な 検 討 を 行 っ た c陽 性 度 に つ い て は,陰 性(-);陽 性 所 見 が 全 く認 め られ な い も の,弱 陽 性(+);少 なく と も1個 の 陽 性 細 胞 が 認 め られ る も の,中 陽 性(廾); 10%以 管 部 に お い て は,散 在 性 に 弱 陽 性 像 が 認 め ら れ た(写 真 3), 上,半 数 未 満 の 陽 性 細 胞 が 認 め られ る も の,お 15 に癌胞 巣 辺 縁 に多 くの 陽 性 細 胞 が 認 め られ た(写 真2).腺

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6 1) Stewart, F.W., Foote, F.W., et al.: Mucoepidermoid tumours of salivary glands. Ann Surg 122: ) Seifert, G.: Histological Typing of Salivary Gland Tumours, 2 nd Ed, Springer- Verlarg, Berlin, ) Thackray, A.C.: Histological Typing of Salivary Gland Tumours. Springer- Verlarg, Berlin, ) Melrose, R.J., Abrams, A.M., et al.: Mucoepidermoid tumor of the intraoral minor salivaly glands: A clinicopathologic study of 54 cases. J Oral Pathol 2: ) Jacobson, P.A., Blank, C., et al.: Mucoepidermoid carcinoma of the Parotid gland. Cancer 22: ) Healey, W.V., Perzin, K. H., et al.: Mucoepidermoid carcinoma of salivary gland origin: classification, clinical-pathologic correlation, and results of treatments. Cancer 26: ) Hall, P.A. and Woods, A.L.: Immunohistochemical makers of cellular proliferation: achievements, problems and prospects. Cell Tissue Kinet 23: ) Robbin, B.A., de la Vega, D., et al.:

7 Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies. Arch Pathol Lab Med 111: ) Scott, R.J., Hall, P.A., et al.: A comparison of immunohistochemical makers of cell proliferation with experimentally determined growth fraction. J Pathol 165: ) Hall, P.A., Levison, D.A., et al.: Proliferation cell nuclear antigen (PCNA) immunohistochemicalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasm. J Pathol 162: ) Wolf, H.K. and Dittrich, K.L.: Detection of proliferation cell nuclear antigen in diagnostic histopathology. J Histochem Cytochem 40: ) Akiyama T., Sudo C., et al.: The product of the human c-erbb- 2 gene; a 185- kilodalton glycoprotein with tyrosinekinase activity. Science 232: ) De Potter, C. R., Quatacker, J., et al: The subcelluar localization of the neu protein in human normal and neoplastic cells Int J Cancer ) Bacus, S.S., Kiguchi, K., et al.: Differentiation of cultured human breast cancer cells (AU-565 and MCF- 7 ) associated with loss of cell surface HER- 2 /nue antigen. Mol Carcinogenesis 3: ) Venter D.J., Tuzi N.L., et al.: Overexpression of the c-erbb- 2 oncoprotein in human breast carcinomas; immunohistochemical assessment correlates with gene amplification. Lancet 2: ) Yonemura Y,. Ninomiya I., et al.: Evaluation of immunoreactivity for erbb- 2 protein as a poor prognosis in gastric cancer. Cancer Res 51: ) O'Reilly, S.M., Barnes, D.M., at al.: The relationship between c-erbb- 2 expression, S-phase fraction and prognosis in breast cancer. Br J Cancer 63:

1) Asa, S. L., et al.: Immunohistochemical localization of neuron-specific enolase in the human hypophysis and pituitary adenoma, Arch. Pathol. Lab. Med., 108: 40 `43, 1984. 2) Chi, B. H. and Kim, R. C.:

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