Tuberc Respir Dis.  1999 Aug;47(2):150-160. 10.4046/trd.1999.47.2.150.

Study on the Clonality of Endothelial Cell Proliferation in Plexiform Lesions in Patients with Pulmonary Hypertension Associated with CREST Syndrome

• Lee SD
• Jeon YG
• Lee JH
• Shim TS
• Lim CM
• Koh YS
• Kim WS
• Kim DS
• Kim WD
• Tuder RM

• KMID: 2050170
• DOI: http://doi.org/10.4046/trd.1999.47.2.150

Abstract

BACKGROUND: The CREST syndrome is an indolent form of progressive systemic sclerosis. Although its clinical progress is indolent, pulmonary hypertension(PH) associated with CREST syndrome have grave prognosis with over 40 percent mortality rate at 2 year follow-up. But the pathogenesis of pulmonary hypertension in this disease is not known, and classified as either primary or secondary PH. Clonality of endothelial cell proliferation in plexiform lesion is a molecular marker which allows distinction between primary and secondary PH. We performed this study to know whether the PH associated with CREST syndrome is a variant of primary PH or is a secondary PH.
METHODS
We assessed the X-chromosome inactivation based on the methylation pattern of the human androgen-receptor gene by PCR(HUMARA). Endothelial cells in plexiform lesions from female patients(n=3) with PH associated with CREST syndrome were microdissected from paraffin blocks. Vascular smooth muscle cells and lung parenchyma were also microdissected for clonality studies.
RESULTS
The proliferating endothelial cells in 14 plexiform lesions were all polyclonal. Similarly proliferated smooth muscle cells from 5 vessels with medial hypertrophy were also polyclonal.
CONCLUSION
These results suggest that the pulmonary hypertension associated with CREST syndrome has different pathogenesis from primary PH and to be classified as secondary PH.

Keyword

CREST syndrome; Pulmonary hypertension; Clonality; Plexiform lesion

MeSH Terms

CREST Syndrome*
Endothelial Cells*
Female
Follow-Up Studies
Humans
Hydrogen-Ion Concentration
Hypertension, Pulmonary*
Hypertrophy
Lung
Methylation
Mortality
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Paraffin
Prognosis
Scleroderma, Diffuse
Paraffin