Lymphangiogenesis in lymphangioleiomyomatosis: Its implication in the progression of lymphangioleiomyomatosis

Toshio Kumasaka, Kuniaki Seyama, Keiko Mitani, Teruhiko Sato, Sanae Souma, Takashi Kondo, Seiji Hayashi, Masato Minami, Toshimasa Uekusa, Yoshinosuke Fukuchi, Koichi Suda

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Lymphangioleiomyomatosis (LAM) is characterized by the proliferation of abnormal smooth muscle cells (LAM cells) in the lungs, lymph nodes, and/or other organs. We examined lymphangiogenesis using immunohistochemistry for Flt-4 (VEGFR-3), a new specific marker for lymphatic endothelial cells, as well as the expression of vascular endothelial growth factor (VEGF)-C in LAM. Specimens were obtained from 6 autopsy cases, a single lung transplant case, and 8 surgical cases for analyses. We demonstrated that lymphatics were extremely abundant in both pulmonary and extrapulmonary LAM and that lymphatic endothelial cells not only proliferated encompassing LAM foci but also infiltrated the intra-LAM foci, and that in advanced LAM, lymphangiogenesis involved vascular walls and interstitium surrounding the area where LAM cells proliferate. In contrast, angiogenesis, confirmed with CD31 immunostaining, was observed less in the LAM foci. LAM cells demonstrated positive reactivity against anti-VEGF-C antibody at varying intensities. Significant correlation (P < 0.001) was noted between the degree of lymphangiogenesis in LAM or VEGF-C expression on LAM cells and lymphagioleiomyomatosis histologic score (LHS), which represents the histologic severity of pulmonary LAM and has been reported to have prognostic significance. Our study is likely to provide a novel point of view on the pathophysiologic significance of lymphangiogenesis in LAM.

Original languageEnglish
Pages (from-to)1007-1016
Number of pages10
JournalAmerican Journal of Surgical Pathology
Volume28
Issue number8
DOIs
Publication statusPublished - 2004 Aug 1

Keywords

  • Lymphangiogenesis
  • Lymphangioleiomyomatosis
  • Lymphatic endothelial cells
  • VEGFR-3
  • Vascular endothelial growth factor-C

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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    Kumasaka, T., Seyama, K., Mitani, K., Sato, T., Souma, S., Kondo, T., Hayashi, S., Minami, M., Uekusa, T., Fukuchi, Y., & Suda, K. (2004). Lymphangiogenesis in lymphangioleiomyomatosis: Its implication in the progression of lymphangioleiomyomatosis. American Journal of Surgical Pathology, 28(8), 1007-1016. https://doi.org/10.1097/01.pas.0000126859.70814.6d