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. 2008 Sep 15;178(6):558-64.
doi: 10.1164/rccm.200709-1369PP. Epub 2008 Jun 12.

The cancer paradigm of severe pulmonary arterial hypertension

Pradeep R Rai  1 , Carlyne D Cool, Judy A C King, Troy Stevens, Nana Burns, Robert A Winn, Michael Kasper, Norbert F Voelkel
Affiliations

The cancer paradigm of severe pulmonary arterial hypertension

Pradeep R Rai et al. Am J Respir Crit Care Med. .

Abstract

The plexiform lesions of severe pulmonary arterial hypertension (PAH) are similar in histologic appearance, whether the disease is idiopathic or secondary. Both forms of the disease show actively proliferating endothelial cells without evidence of apoptosis. Here, we discuss the pathobiology of the atypical, angioproliferative endothelial cells in severe PAH. The concept of the endothelial cell as a "quasi-malignant" cell provides a new framework for antiproliferative, antiangiogenic therapy in severe PAH.

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Figures

<b>Figure 1.</b>
Figure 1.
Pathogenetic concepts of severe pulmonary arterial hypertension: a paradigm shift.
<b>Figure 2.</b>
Figure 2.
Hematoxylin-and-eosin–stained section from a lung of a patient with idiopathic pulmonary arterial hypertension demonstrating the intraluminal proliferation of endothelial cells that occurs in severe angioproliferative pulmonary hypertension. Arrows indicate the bland, flattened endothelial cells lining the lumen of newly formed vessels. The upper right inset shows a higher power view of the endothelial cells that comprise these lesions.
<b>Figure 3.</b>
Figure 3.
A panel of plexiform lesions demonstrates the expression pattern of several markers of malignancy. (A) Expression of p16 in the central part of two plexiform lesions (in proximal portions of bifurcating vessels). (B) Highly expressed β-catenin. (C) Luminal endothelial cell expression of multiple drug resistance protein (MDRP) in a plexiform lesion. (D) Increased expression of survivin in central portion of plexiform lesion. (E) Dense expression of chemokine receptor (CXCR)-4 in a plexiform lesion. (F) Expression of epithelial growth factor receptor (EGFR)-3 in a plexiform lesion.
<b>Figure 4.</b>
Figure 4.
Plexiform lesions (*) from patients with severe pulmonary arterial hypertension. (A) Loss of Wnt7a can be seen in the endothelial cells of this lesion. Note the maintained Wnt7a expression in the surrounding lung parenchyma. (B) A similar loss of activated leukocyte adhesion molecule (ALCAM)-1 expression is seen in this lesion.
<b>Figure 5.</b>
Figure 5.
Immunohistochemical stain for CD117 (c-kit). (A) CD117 cells are scattered throughout the vascular lesion. Mast cells can also stain for CD117. However, serial sections stained for mast cells showed no mast cells in this lesion (not shown) and rare mast cells in other lesions. (B) Hematoxylin-and-eosin–stained section of a plexiform lesion and surrounding lung parenchyma illustrates megakaryocytes (arrows) around the lesion. The inset shows the multilobulated appearance of these cells.
See this image and copyright information in PMC

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