Prognostic significance of stromal platelet-derived growth factor beta-receptor expression in human breast cancer.
This study systematically analyzes platelet-derived growth factor (PDGF) receptor expression in six types of common tumors as well as examines associations between PDGF beta-receptor status and clinicopathological characteristics in breast cancer. PDGF receptor expression was determined by immunohistochemistry on tumor tissue microarrays. Breast tumor data were combined with prognostic factors and related to outcome endpoints. PDGF alpha- and beta-receptors were independently expressed, at variable frequencies, in the tumor stroma of all tested tumor types. There was a significant association between PDGF beta-receptor expression on fibroblasts and perivascular cells in individual colon and prostate tumors. In breast cancer, high stromal PDGF beta-receptor expression was significantly associated with high histopathological grade, estrogen receptor negativity, and high HER2 expression. High stromal PDGF beta-receptor expression was correlated with significantly shorter recurrence-free and breast cancer-specific survival. The prognostic significance of stromal PDGF beta-receptor expression was particularly prominent in tumors from premenopausal women. Stromal PDGF alpha- and beta-receptor expression is a common, but variable and independent, property of solid tumors. In breast cancer, stromal PDGF beta-receptor expression significantly correlates with less favorable clinicopathological parameters and shorter survival. These findings highlight the prognostic significance of stromal markers and should be considered in ongoing clinical development of PDGF receptor inhibitors.
Paulsson
Janna
J
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
Sjöblom
Tobias
T
Micke
Patrick
P
Pontén
Fredrik
F
Landberg
Göran
G
Heldin
Carl-Henrik
CH
Bergh
Jonas
J
Brennan
Donal J
DJ
Jirström
Karin
K
Ostman
Arne
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020286:Pericytes / Q000378:metabolism*; D017697:Premenopause; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D020574:Proto-Oncogene Proteins c-sis; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen