This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wada, H. Articles by Murata, Y. Search for Related Content PubMed PubMed Citation Articles by Wada, H. Articles by Murata, Y.

Molecular Evidence That Most but not All Carcinosarcomas of the Uterus Are Combination Tumors

Departments of Obstetrics and Gynecology [H. W., T. E., M. F., K. Y., R. N., H. K., Y. M.] and Radiation Biology [H. W., T. H., T. N.], Osaka University Faculty of Medicine, 2-2, Yamadaoka, Suita, Osaka 565, Japan; Department of Pathology, Osaka City University Hospital, Osaka 545, Japan [T. H., K. W.]; Department of Pathology, Osaka Police Hospital, Osaka 543, Japan [M. T.]; and Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado 80262 [K. R. S.]

The pathogenesis of carcinosarcoma is still a subject of controversy. In the present study, molecular techniques were applied to determine the pathogenesis of uterine carcinosarcomas. The patterns of chromosome X inactivation were analyzed, targeting a portion of exon 1 of the human androgen receptor (HUMARA) in malignant epithelial and mesenchymal components. The presence of p53 and K-ras mutations were also analyzed. H&E-stained sections of paraffin-embedded, formalin-fixed tissues were microdissected to obtain both epithelial and nonepithelial lesions from 25 carcinosarcomas, and DNAs were extracted by proteinase K digestion. Following treatment with methylation-sensitive restriction endonuclease (HhaI or HpaII), PCR amplification was performed using nested primers targeted to the HUMARA locus. Mutations in the p53 gene and K-ras gene were found in eight (32%) and six (24%) tumors, respectively. The patterns of chromosome X inactivation were different between the carcinomatous and sarcomatous components of three carcinosarcomas, indicating that these three tumors represent collision tumors. By contrast, the patterns of chromosome X inactivation, K-ras sequence, and p53 sequence were identical in both carcinomatous and sarcomatous components in 21 carcinosarcomas, indicating that these 21 tumors represent combination tumors. One case produced equivocal results that precluded determination of whether it represented a collision or combination tumor. These observations show that although most carcinosarcomas are combination tumors, some develop as collision tumors. The determination of histogenesis in individual cases of carcinosarcoma using molecular markers may be worthwhile, because the result could help predict the prognosis of individual cases and help guide clinical management.

¹ To whom requests for reprints should be addressed. Phone: 81-6-879-3355; Fax: 81-6-879-3359; E-mail: enomoto@gyne.med.osaka-u.ac.jp.

Received 7/ 7/97. Accepted 10/ 3/97.

This article has been cited by other articles:

				R. Gupta, S. Singh, S. Hedau, S. Nigam, B. C Das, I. Singh, and A. K. Mandal Spindle cell carcinoma of head and neck: an immunohistochemical and molecular approach to its pathogenesis J. Clin. Pathol., May 1, 2007; 60(5): 472 - 475. [Abstract] [Full Text] [PDF]

				G. L. Maxwell, G.V.R. Chandramouli, L. Dainty, T. J. Litzi, A. Berchuck, J. C. Barrett, and J. I. Risinger Microarray Analysis of Endometrial Carcinomas and Mixed Mullerian Tumors Reveals Distinct Gene Expression Profiles Associated with Different Histologic Types of Uterine Cancer Clin. Cancer Res., June 1, 2005; 11(11): 4056 - 4066. [Abstract] [Full Text] [PDF]

				J. P. van Dijk, L. H. Heuver, B. A. van der Reijden, R. A. Raymakers, T. de Witte, and J. H. Jansen A Novel, Essential Control for Clonality Analysis with Human Androgen Receptor Gene Polymerase Chain Reaction Am. J. Pathol., September 1, 2002; 161(3): 807 - 812. [Abstract] [Full Text] [PDF]

				W G McCluggage Malignant biphasic uterine tumours: carcinosarcomas or metaplastic carcinomas? J. Clin. Pathol., May 1, 2002; 55(5): 321 - 325. [Abstract] [Full Text] [PDF]

				J. D. Potter Morphostats: A Missing Concept in Cancer Biology Cancer Epidemiol. Biomarkers Prev., March 1, 2001; 10(3): 161 - 170. [Abstract] [Full Text]

				R. M. Reis, D. Konu-Lebleblicioglu, J. M. Lopes, P. Kleihues, and H. Ohgaki Genetic Profile of Gliosarcomas Am. J. Pathol., February 1, 2000; 156(2): 425 - 432. [Abstract] [Full Text] [PDF]

				H. Fujii, M. Yoshida, Z. X. Gong, T. Matsumoto, Y. Hamano, M. Fukunaga, R. H. Hruban, E. Gabrielson, and T. Shirai Frequent Genetic Heterogeneity in the Clonal Evolution of Gynecological Carcinosarcoma and Its Influence on Phenotypic Diversity Cancer Res., January 1, 2000; 60(1): 114 - 120. [Abstract] [Full Text]