PATHOPHYSIOLOGY

Leiomyoma Development
1. Chromosomal Aberrations
2. Hormones
3. Growth Factors
 Leiomyoma Development
1. Chromosomal Aberrations
• Chromosomes 6, 7, 12 & 14
• Disruption or dysregulation of the high mobility
group genes on chromosome 12
• Chromosomes 12 and 7 involve genes that may
regulate growth-inducing proteins including:
• TGF-B
• EGF
• IGFs 1 & 2
 Leiomyoma Development
2. Growth Factors
• EGF
– increases DNA synthesis in myoma cells
• IGFs 1& 2
– increase cell proliferation by activation of the
MAPK (mitogen activated protein kinase) pathway
• VEGF
– promotes angiogenesis
• ECM
– reservoir of growth factors
– composed of fibronectin and proteoglycans, all
involved in remodelling and growth of myomas
 Leiomyoma Development
3. Hormones
• Estrogen
- Induces mature leiomyoma cells to release mitogenic
stimuli to adjacent immature cells
- Increases tissue sensitivity to progesterone by
increasing the availability of progesterone receptors
• Progesterone
- Completes the development and proliferation of
leiomyoma cells
 Growth Factors Hormones
Chromosomal • EGF • Estrogen
Aberrations • VEGF • Progesterone
• IGFs 1 & 2

Proliferation Myometrial Proliferation

Differentiation Angiogenesis
Leiomyoma
Hyperplasia
ECM deposition