Expression of apoptosis-related proteins, p53, and DNA fragmentation in sarcomas of the pulmonary artery

BACKGROUND. Apoptosis is a common feature in a variety of pathologic condit ions. Induction of apoptosis through apoptotic stimuli such as, chemotherap y or radiation, presents new insights into tumor biology and therapy. In pa rticular, members of the Bcl-2 family as well as the Fas system are known t o be involved in the regulation of apoptosis in different tumor entities. METHODS. in the current study, the expression of the apoptosis-related mole cules p53, Bax, Bcl-2, Fas (CD95), Fas-Ligand and perforin was examined in 7 patients with a sarcoma of the pulmonary artery. Furthermore, the TUNEL-m ethod for the detection of apoptotic cells was applied as well as sequencin g of the p53 gene. RESULTS. In the TUNEL assay, approximately 10% of the sarcoma cells display ed DNA fragmentation. In addition, Bax was expressed in tumor cells. Accumu lation of p53 was evident in 4 of 7 patients (pAB 240 antibody), and 2 of t hem were positive for the pAB 1801 antibody. Only 1 case had a point mutati on in Exon 5 of of the p53 sequence. A few tumor cells showed a double labe ling of Bax and p53. Bcl-2 could be detected only in tumor-associated lymph ocytes. Finally, several lymphocytes could be stained with perforin, but no ne of the specimens showed a reactivity for Fas or Fas-Ligand. CONCLUSION. The expression of Bax indicated a possible role of this molecul e in programmed cell death in pulmonary sarcomas. The limited coexpression of Bax and p53 suggested that induction of Bax can occur independently of p 53. The detection of perforin in lymphocytes suggested a possible role for this molecule in apoptosis of the sarcoma cells. In contrast, the Fas syste m did not seem to play an essential role in sarcomas of the great vessels. (C) 2001 American Cancer Society.