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 conditions. Induction of apoptosis through apoptotic stimuli such as, chemotherapy or radiation, presents new insights into tumor biology and therapy. In particular, members of the Bcl-2 family as well as the Fas system are known to be involved in the regulation of apoptosis in different tumor entities.


METHODS
In the current study, the expression of the apoptosis-related molecules 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-method for the detection of apoptotic cells was applied as well as sequencing of the p53 gene.


RESULTS
In the TUNEL assay, approximately 10% of the sarcoma cells displayed DNA fragmentation. In addition, Bax was expressed in tumor cells. Accumulation of p53 was evident in 4 of 7 patients (pAB 240 antibody), and 2 of them were positive for the pAB 1801 antibody. Only 1 case had a point mutation in Exon 5 of the p53 sequence. A few tumor cells showed a double labeling of Bax and p53. Bcl-2 could be detected only in tumor-associated lymphocytes. Finally, several lymphocytes could be stained with perforin, but none of the specimens showed a reactivity for Fas or Fas-Ligand.


CONCLUSIONS
The expression of Bax indicated a possible role of this molecule in programmed cell death in pulmonary sarcomas. The limited coexpression of Bax and p53 suggested that induction of Bax can occur independently of p53. The detection of perforin in lymphocytes suggested a possible role for this molecule in apoptosis of the sarcoma cells. In contrast, the Fas system did not seem to play an essential role in sarcomas of the great vessels.
Gaumann
A
A
Institute of Pathology, University of Mainz, Mainz, Germany. a.gaumann@Kerckhoff.mpg.de
Tews
D S
DS
Mayer
E
E
Dahm
M
M
Petrow
P K
PK
Otto
M
M
Kirkpatrick
C J
CJ
Kriegsmann
J
J
D000328:Adult; D017209:Apoptosis / Q000235:genetics; D053938:DNA Fragmentation; D004252:DNA Mutational Analysis; D053222:Fas Ligand Protein; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011651:Pulmonary Artery; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D019043:Vascular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
C494826:BAX protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D054353:Perforin