Summary
Histopathological examination of thymomas often fails to predict their malignant potential because the morphology of invasive or metastatic thymomas does not differ significantly from that of benign, encapsulated thymomas. In order to find a marker of aggressiveness in thymoma, 21 cases (9 noninvasive, 8 invasive and 4 metastatic thymomas) were examined for expression of the ras oncogene product p21 by immunohistochemistry and immunoblot analysis. Immunohistochemical study, using a serially diluted monoclonal antibody, NCC-RAS-001, demonstratd that neoplastic thymoma cells generally contained more p21 than normal thymic epithelial cells. Immunoblot analysis using another monoclonal antibody (NCC-RAS-004) also confirmed the increased concentration of p21 in all but one of the thymomas by comparison with normal thymic tissue. One metastatic thymoma did not have a band of p21 recognized by NCC-RAS-004 and was believed to have a deletion of the epitope recognized by this antibody. In addition, another metastatic thymoma showed abnormal electrophoretic mobility of p21. The increasd amount of p21 in thymomas suggests that this protein has a role in the oncogenesis or progression of thymoma. The high incidence of a p21 molecular abnormality in metastatic thymomas indicates that the abnormality of this protein could be used as a possible marker of aggressive behavior.
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References
Clair T, Miller WR, ChoChung YS (1987) Prognostic significance of the expression of a ras protein with molecular wight of 21000 by human beast cancer. Cancer Res 47:5290–5293
Fromowitz FB, Viola MV, Chao S, Oravez S, Mishriki Y, Finkel G, Grimson R, Lundy J (1987) ras p21 expression in the progression of breast cancer. Hum Pathol 18:1268–1275
Ghosh AK, Moore M, Harris M (1986) Immunohistochemical de tection of ras oncogene p21 product in benign and malignant mammary tissue in man. J Clin Pathol 39:428–434
Johnson TL, Lloyd RV, Thor A (1987) Expression of ras oncogene p21 antigen in normal and proliferative thyroid tissues. Am J Pathol 127:60–65
Kanai T, Hirohashi S, Noguchi M, Shimoyama Y, Shimosato Y, Noguchi S, Nishimura N, Abe O (1987) Monoclonal antibody highly sensitive for the detection of ras p21 in immunoblotting analysis. Jpn J Cancer Res (Gann) 78:1314–1318
Kodama T, Watanabe S, Sato Y, Shimosato Y, Miyazawa N (1986) An immunohistochemical study of thymic epithelial tumors. I. Epithelial component. Am J Surg Pathol 10:26–33
Koshiishi Y, Noguchi M, Nakajima T, Hirohashi S, Shimosato Y, Hayata Y (1989) Immunohistochemical and immunoblot analysis of rasp21 expression in lung carcinomas. Acta Pathol Jpn 39:643–647
Lewis JE, Wick MR, Scheithauer BW, Bernatz PE, Taylor WF (1987) Thymoma. A clinicopathologic review. Cancer 60:2727–2743
Maggi G, Gaiccone G, Donadio M, Ciuffreda L, Dalesio O, Leria G, Trifiletti G, Casadio C, Palestro G, Mancuso M, Calciati A (1986) Thymomas. A review of 169 cases, with particular reference to results of surgical treatment. Cancer 58:765–776
Noguchi M, Hirohashi S, Shimosato Y, Thor A, Schlom J, Tsunok awa Y, Terada M, Sugimura T (1986) Histologic demonstration of antigens reactive with antip21 ras monoclonal antibody (RAP-5) in human stomach cancers. J Natl Cancer Inst 77:379–385
Radosevich JA, Gould VE, Ma Y, Lee I, Thor A, Carney WP, Warren WH, Schlom J, Rosen ST (1989) Immunohistochemical analysis of normal and mutated ras oncogene p21 expression in human pulmonary and pleural neoplasms. Virchows Arch [B] 56:377–383
Rosai J, Levin GD (1976) Tumors of the thymus. Atlas of tumor pathology, second series, fascicle 13, Armed Forces Institute of Pathology, Washington, D.C.
Samowitz WS, Pauli G, Hamilton SR (1988) Reported binding of monoclonal antibody RAP-5 to formalinfixed tissue sections is not indicative of ras p21 expression. Hum Pathol 19:127–132
Sato Y, Watanabe S, Mukai K, Kodama T, Upton MP, Goto M, Shimosato Y (1986) An immunohistochemical study of thymic epithelial tumors. II. Lymphoid component. Am J Surg Pathol 10:862–870
Tanaka T, Slamon DJ, Battifora H, Cline MJ (1986) Expression of p21 ras oncoproteins in human cancers. Cancer Res 46:1465–1470
Thor A, Ohuchi N, Hand PH, Callahan R, Weeks MO, Theillet C, Lidereau R, Escot C, Page DL, Vilasi V, Schlom J (1986) ras gene alteration and enhanced levels of ras p21 expression in a spectrum of benign and malignant human mammary tis sues. Lab Invest 55:603–615