The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma

Harriet O. Smith, Patrick S. Anderson, Dennis Yi-Shin Kuo, Gary L. Goldberg, Carol L. DeVictoria, Christine A. Boocock, Joan G. Jones, Carolyn D. Runowicz, E. Richard Stanley, Jeffrey W. Pollard

Research output: Contribution to journalArticle

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Abstract

Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (GSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 ± 1.8 μg/liter) were significantly elevated compared with levels found in the 32 controls (3.5 ± 1.1 μg/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%), with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and < 0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the expression of the protein in these tissues. Reverse transcription-PCR demonstrated the presence of mRNA for both the transmembrane and secreted forms of CSF-1 in all tumors analyzed. These results therefore support the hypotheses that CSF-1 and CSF-1R are overexpressed in endometrial adenocarcinoma, that levels of expression significantly correlate with clinicopathological risk factors for poor outcome, and that CSF-1 in association with its receptor via autocrine, juxtacrine, and/or paracrine interactions has a causal role in endometrial adenocarcinoma development and proliferation.

Original languageEnglish (US)
Pages (from-to)313-325
Number of pages13
JournalClinical Cancer Research
Volume1
Issue number3
StatePublished - Mar 1995

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Macrophage Colony-Stimulating Factor
Adenocarcinoma
Staining and Labeling
Serum
Epithelium
fms Genes
Colony-Stimulating Factor Receptors
Neoplasms
Messenger RNA
Receptor Protein-Tyrosine Kinases
Endometrial Neoplasms
Phagocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Smith, H. O., Anderson, P. S., Kuo, D. Y-S., Goldberg, G. L., DeVictoria, C. L., Boocock, C. A., ... Pollard, J. W. (1995). The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma. Clinical Cancer Research, 1(3), 313-325.

The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma. / Smith, Harriet O.; Anderson, Patrick S.; Kuo, Dennis Yi-Shin; Goldberg, Gary L.; DeVictoria, Carol L.; Boocock, Christine A.; Jones, Joan G.; Runowicz, Carolyn D.; Stanley, E. Richard; Pollard, Jeffrey W.

In: Clinical Cancer Research, Vol. 1, No. 3, 03.1995, p. 313-325.

Research output: Contribution to journalArticle

Smith, HO, Anderson, PS, Kuo, DY-S, Goldberg, GL, DeVictoria, CL, Boocock, CA, Jones, JG, Runowicz, CD, Stanley, ER & Pollard, JW 1995, 'The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma', Clinical Cancer Research, vol. 1, no. 3, pp. 313-325.
Smith, Harriet O. ; Anderson, Patrick S. ; Kuo, Dennis Yi-Shin ; Goldberg, Gary L. ; DeVictoria, Carol L. ; Boocock, Christine A. ; Jones, Joan G. ; Runowicz, Carolyn D. ; Stanley, E. Richard ; Pollard, Jeffrey W. / The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma. In: Clinical Cancer Research. 1995 ; Vol. 1, No. 3. pp. 313-325.
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abstract = "Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (GSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 ± 1.8 μg/liter) were significantly elevated compared with levels found in the 32 controls (3.5 ± 1.1 μg/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50{\%}) and elevated staining for CSF-1 (41 of 54 cases, 75.9{\%}), with intense staining of CSF-1 in 16 of 54 cases (29.6{\%}). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and < 0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the expression of the protein in these tissues. Reverse transcription-PCR demonstrated the presence of mRNA for both the transmembrane and secreted forms of CSF-1 in all tumors analyzed. These results therefore support the hypotheses that CSF-1 and CSF-1R are overexpressed in endometrial adenocarcinoma, that levels of expression significantly correlate with clinicopathological risk factors for poor outcome, and that CSF-1 in association with its receptor via autocrine, juxtacrine, and/or paracrine interactions has a causal role in endometrial adenocarcinoma development and proliferation.",
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AU - Goldberg, Gary L.

AU - DeVictoria, Carol L.

AU - Boocock, Christine A.

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AU - Pollard, Jeffrey W.

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