title: Expression of proto-oncogene cFMS protein in lung, breast, and ovarian cancers.
abstract: We performed immunohistochemistry for macrophage colony-stimulating factor 1 receptor (also known as c-fms proto-oncogene product) on tissue microarrays of human nontumor lung, pulmonary squamous cell carcinomas (SCC) and adenocarcinomas (ADC), and breast and ovarian carcinomas using a commercially available anti-cFMS antibody. The specificity of the antibody was validated by Western blot and mass spectrometry analysis. Staining of cFMS was restricted to stromal fibroblasts in pulmonary SCC and ADC specimens and was not identified in tumor epithelium or epithelium and stromal cells of nontumor lung. Evaluation of pulmonary SCC (n=63) and ADC (n=71) specimens revealed stromal fibroblast cFMS staining in 60% (38 of 63) and 35% (25 of 71) of the tumor samples, respectively. A similar pattern of stromal fibroblast cFMS staining was observed in breast (n=21) and ovarian (n=50) carcinomas. It was reported that glucocorticoids induced cFMS expression in breast carcinomas and choriocarcinomas. To investigate whether stromal cFMS expression in lung cancers was associated with glucocorticoid signaling, glucocorticoid receptor protein distribution was evaluated in lung tissue microarrays by immunohistochemistry. Stromal fibroblast glucocorticoid receptor staining was only observed in 18% (2 of 11) of pulmonary SCC and 6% (1 of 17) of ADC specimens, suggesting that cFMS expression may not be directly mediated by glucocorticoids in stromal fibroblasts of lung cancers. The tumor stromal cell expression of cFMS in certain tumor types (lung, ovarian, and breast) suggests the potential for more diverse tumor therapeutic options and presents an attractive target for drug development.
authors.affiliation: *Drug Safety Research and Development, Pfizer Inc., Groton, CT †Drug Safety Research and Development, Pfizer Inc., San Diego, CA ‡Analytical Research and Development, Pfizer Inc., St. Louis, MO.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kakiuchi-Kiyota
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Lappin
authors.forename: Catherine
authors.initials: C
authors.lastname: Heintz
authors.forename: Paul W
authors.initials: PW
authors.lastname: Brown
authors.forename: Flavia O
authors.initials: FO
authors.lastname: Pinho
authors.forename: Anne M
authors.initials: AM
authors.lastname: Ryan
authors.forename: Nagappan
authors.initials: N
authors.lastname: Mathialagan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D058990:Molecular Targeted Therapy; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016186:Receptor, Macrophage Colony-Stimulating Factor