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

Abstract

The characterization of clinical, histopathological, immunohistochemical, and genetic features of intimal sarcomas arising in the pulmonary artery is presented in this study. Four resected lungs, one endarterectomy specimen and 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 hybridization (CGH) were analyzed. The predominant clinical presentation was dyspnea (all eight patients) and febrile pulmonary disease (six of eight). Signs of embolic lung disease were present in all patients. One patient died postoperatively, six patients died of disease 8-35 months after presentation, and one patient was alive 6 months after surgery. Histopathological examination of the submitted material showed spindle cell, partially myxoid and pleomorphic sarcomas. Metastases were histologically confirmed in three patients (lung, pleura, and skull). Immunohistochemically, vimentin was strongly expressed in all tumors. Focal positivity was observed for alpha smooth muscle actin, CD117, CD68, p53, and bcl2. No reaction could be obtained for endothelial markers. The proliferation index Ki-67 was between 5% and 80%. Six examined tumors were positive for mdm2. In the CGH analysis, gains and amplifications 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, 5p, 6p, and 11q. Intimal sarcomas of the pulmonary artery are tumors with an unfavorable prognosis and poorly differentiated morphology. A majority of tumors show a consistent genetic alteration (gains and amplifications in the 12q13-14 region) and overexpression of mdm2, implicating the mdm2/p53 pathway as a possible mechanism in the tumor pathogenesis.

Characterization of sarcoma-like cells derived from endarterectomized tissues from patients with CTEPH and establishment of a mouse model of pulmonary artery intimal sarcoma

“…Pulmonary intimal sarcoma is a very uncommon neoplastic tumor of the cardiovascular system, and only about 125 cases have been reported in the literature (8). This tumor is thought to originate from subendothelial-mesenchymal cells of the pulmonary vascular wall (9). Immunohistochemical examinations of intimal sarcoma demonstrated that these tumors undergo endothelial, fibroblastic, or myofibroblastic differentiation (10 (11), while others have indicated that they are only positive for vimentin, but not for desmin or α-SMA (12).…”

Coactivated Platelet-Derived Growth Factor Receptor α and Epidermal Growth Factor Receptor Are Potential Therapeutic Targets in Intimal Sarcoma

“…Presumably, these sarcomas develop from the subendothelial cells of the blood vessel wall located in the intima (14). The defining feature is the predominant intraluminal growth with obstruction of the lumen of the vessel of origin and embolic tumor dissemination (15).…”

Uncommon Case of Brain Metastasis in a Patient with a History of Heavy Smoking

“…In a high percentage of intimal sarcomas (70%-80%), overexpression of the Mdm2 protein can be observed 19,20 ; however, this finding is not specific, because many other tumours can also show this staining pattern.…”