Virchows Archiv

, Volume 441, Issue 1, pp 53–62

Cell proliferation and apoptosis in human uterine leiomyomas and myometria

  • Darlene Dixon
  • Gordon P. Flake
  • Alicia B. Moore
  • Hong He
  • Joseph K. Haseman
  • John I. Risinger
  • Johnathan M. Lancaster
  • Andrew Berchuck
  • Carl J. Barrett
  • Stanley J. Robboy
Original Article

DOI: 10.1007/s00428-001-0568-7

Cite this article as:
Dixon, D., Flake, G.P., Moore, A.B. et al. Virchows Arch (2002) 441: 53. doi:10.1007/s00428-001-0568-7

Abstract.

To determine the role of cell proliferation and apoptosis in uterine leiomyoma growth, we studied protein expression of two major regulatory proteins of apoptosis – Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic) – and two endogenous markers of cell replication – proliferating cell nuclear antigen (PCNA) and Ki-67 – in tumors and matched myometrium from premenopausal women. Conventional mitotic indices also were determined, and all proliferation data were correlated to tumor size. In situ end-labeling of fragmented DNA and routine histology were used to assess apoptosis. Our results showed that the apoptosis-regulating proteins (Bcl-2 and Bax) were expressed in the cytoplasm of the leiomyoma and myometrial smooth muscle cells throughout the menstrual cycle. Bax expression differed from Bcl-2 in that it also was found in the cytoplasm of vascular smooth muscle cells of the myometria and tumors. Both tumors and myometrial samples expressed 26-kDa and 21-kDa proteins that reacted with antibodies directed towards Bcl-2 and Bax, respectively. Apoptosis was not a prominent feature of uterine leiomyomas or myometrium. PCNA- and Ki-67-labeling and mitotic counts were significantly (P<0.05) higher in leiomyomas than in matched myometrial samples. Proliferative activity was variable for individual tumors of the same patient and independent of tumor size. Our results suggest that altered apoptosis by overexpression of Bcl-2 or by decreased expression of Bax does not appear to be a major factor in uterine leiomyoma growth. We conclude that increased cell proliferation is the most significant contributor to growth and that the proliferative state is autonomous for each tumor in a given patient and is independent of tumor size.

Leiomyoma Proliferation Apoptosis Bcl-2 Bax Immunohistochemistry

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Darlene Dixon
    • 1
  • Gordon P. Flake
    • 1
  • Alicia B. Moore
    • 1
  • Hong He
    • 1
  • Joseph K. Haseman
    • 2
  • John I. Risinger
    • 3
  • Johnathan M. Lancaster
    • 4
  • Andrew Berchuck
    • 4
  • Carl J. Barrett
    • 3
  • Stanley J. Robboy
    • 4
  1. 1.Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, MDC2-09, Research Triangle Park, NC 27709, USAUSA
  2. 2.Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USAUSA
  3. 3.Laboratory of Biosystems and Cancer, National Cancer Institute, Bethesda, MD 20892, USAUSA
  4. 4.Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USAUSA
  5. 5.Department of Pathology, Duke University Medical Center, Durham, NC 27710, USAUSA