Gains of 12q13-14 and overexpression of mdm2 are frequent findings in intimal sarcomas of the pulmonary artery

The characterization of clinical, histopathological, immunohistochcmical, a nd genetic features of intimal sarcomas arising in the pulmonary artery is presented in this study. Four resected lungs, one endarterectomy specimen a nd three biopsies from eight patients (four males and four females; median age 41 years) suffering from intimal sarcomas of the pulmonary artery using conventional stains, immunohistochemistry, and comparative genomic hybridi zation (CGH) were analyzed. The predominant clinical presentation was dyspn ea (all eight patients) and febrile pulmonary disease (six of eight). Signs of embolic lung disease were present in all patients. One patient died pos toperatively, six patients died of disease 8-35 months after presentation, and one patient was alive 6 months after surgery. Histopathological examina tion of the submitted material showed spindle cell, partially myxoid and pl eomorphic sarcomas. Metastases were histologically confirmed in three patie nts (lung, pleura, and skull). Immunohistochemically, vimentin was strongly expressed in all tumors. Focal positivity was observed fur alpha smooth mu scle actin, CD117, CD68, p53, and bc12. No reaction could be obtained for e ndothelial markers. The proliferation index Ki-67 was between 5% and 80%. S ix examined tumors were positive for mdm2. In the CGH analysis, gains and a mplifications in the 12q13-14 region were found in six of eight tumors (75% ). Other, less consistent alterations, were losses on 3p, 3q, 4q, 9p, 11q, 13q, Xp, and Xq, gains on 7p, 17p, and 17q, and amplifications on 4q, 5D, 6 p, and 11q. Intimal sarcomas of the pulmonary artery are tumors with an unf avorable prognosis and poorly differentiated morphology. A majority of tumo rs show a consistent genetic alteration (gains and amplifications in the 12 q13-14 region) and overexpression of mdm2, implicating the mdm2/p53 pathway as a possible mechanism in the tumor pathogenesis.