Gene expression analysis reveals an angiogenic profile in uterine leiomyoma pseudocapsule

Mol Hum Reprod. 2013 Jun;19(6):380-7. doi: 10.1093/molehr/gat007. Epub 2013 Jan 25.

Abstract

The pseudocapsule (PC) of the uterine leiomyoma (UL) is an anatomic entity that surrounds the myoma separating it from the myometrium (UM). Although a number of microarray experiments have identified differences in gene expression profile in the UL when compared with the UM, there is a lack of systematic studies on the PC. In this study, quantitative RT-PCR analysis was performed on 18 matched PC, UL and UM specimens and results showed that the PC displays a specific gene expression profile. The low expression level of insulin-like growth factor (IGF-2), a fibroid specific marker, that we found in the PC and the UM when compared with the UL, clearly indicates that the PC is in structural continuity with the UM. However, the significant increase in endoglin expression level in PC with respect to the UL and UM indicates that an active neoangiogenesis is present in PC. Conversely, other angiogenic factors such as von Willebrand factor (vWF) and vascular endothelial growth factor A (VEGF-A) seem to have little influence on the PC angiogenesis. Because the endoglin is preferentially expressed in proliferating endothelial cells, whereas the vWF and VEGF-A are preferentially expressed in preexisting endothelial cells, our idea is that the angiogenic activity in the PC is linked to wound healing. The angiogenic activity is also sustained by intermediate expression level of cystein-rich angiogenesis inducer 61, connective tissue growth factor and collagen 4α2 genes all involved in the neoangiogenesis, that we detected in the PC. Taken together our data demonstrate that the specific expression pattern observed in the PC could be the response of the uterine wall's smooth cells to the tension imposed by the tumor. As a consequence, a neovascular structure is generated involving regenerative processes. For these reasons, we suggest that the laparoscopic intracapsular myomectomy (LIM), a new surgical technique that preserves the PC during the UL removal, should always be preferred, to favor a faster and proper uterine healing.

Keywords: angiogenesis; endoglin (CD105); fertility; fibroid pseudocapsule; intracapsular myomectomy; uterine leiomyoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Biomarkers / metabolism
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Cysteine-Rich Protein 61 / genetics
  • Cysteine-Rich Protein 61 / metabolism
  • Endoglin
  • Female
  • Gene Expression Profiling
  • Gene Expression*
  • Humans
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / metabolism
  • Leiomyoma / blood supply*
  • Leiomyoma / genetics
  • Leiomyoma / pathology
  • Leiomyoma / surgery
  • Middle Aged
  • Myometrium / blood supply*
  • Myometrium / metabolism
  • Myometrium / pathology
  • Myometrium / surgery
  • Neovascularization, Pathologic
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Uterine Myomectomy / methods
  • Uterine Neoplasms / blood supply*
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / pathology
  • Uterine Neoplasms / surgery
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • von Willebrand Factor / genetics
  • von Willebrand Factor / metabolism

Substances

  • Antigens, CD
  • Biomarkers
  • CCN1 protein, human
  • Collagen Type IV
  • Cysteine-Rich Protein 61
  • ENG protein, human
  • Endoglin
  • IGF2 protein, human
  • Receptors, Cell Surface
  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor
  • Connective Tissue Growth Factor
  • Insulin-Like Growth Factor II