Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast Phyllodes Tumor

Abstract

Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF-) related proteins and the implications in breast phyllodes tumor (PT). Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT) were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFR α/β, and NG2) and analyzed the results according to clinicopathologic parameters. Results. Expression of PDGFRα and PDGFRβ in the stromal component increased with increasing histologic grade of PT (p = 0.003 and p = 0.034, resp.). Among clinicopathologic parameters, only expression of FAPα in stroma was associated with distant metastasis (p = 0.002). In univariate analysis, stromal expression of PDGFRα was associated with shorter overall survival (p = 0.002). In Cox multivariate analysis, stromal overgrowth and PDGFRα stromal positivity were associated with shorter overall survival (p = 0.006 and p = 0.050, resp.). Furthermore, expression of PDGFRβ in stroma was associated with shorter overall survival in patients with malignant PT (p = 0.041). Conclusion. Stromal expression of PDGFRα and PDGFRβ increased with increasing histologic grade of PT. In addition, PDGFR stromal positivity was associated with shorter overall survival. These results suggest that CAFs are associated with breast PT progression.

What is new in cancer-associated fibroblast biomarkers?

“…In a xenograft mouse model of lung cancer, PDGFRα has been shown to promote the recruitment of fibroblasts to the tumor infiltration front. PDGFRα/β high CAFs have also been linked to lymph node metastasis and lymphovascular invasion in ovarian cancer [ 84 ] and pancreatic cancer [ 48 ] and lead to poorer prognosis in breast cancer [ 78 ], ovarian cancer [ 84 ], pancreatic cancer [ 48 ], and lobular breast tumors [ 85 ]. Inhibition of PDGFR signaling can restrain cervical cancer angiogenesis and cell proliferation [ 86 ].…”

Tumor Immunometabolism Characterization in Ovarian Cancer With Prognostic and Therapeutic Implications

“…For example, a cytokine storm induced by M2 macrophages upon new-adjuvant treatment in ovarian cancer promotes tumor growth and progression ( 44 ). As for specific upregulated cytokines, we found that PDGFRB, a molecular marker of CAFs ( 45 ), was highly expressed in C1 ( P < 0.001). CXCL10, upregulated in C2 ( P < 0.001), is a pro-inflammatory cytokine involved in the chemotactic recruitment of macrophages, natural killer cells, dendritic cells, and active T lymphocytes to tumor cells ( 46 ).…”

The relationship between cancer associated fibroblasts biomarkers and prognosis of breast cancer: a systematic review and meta-analysis

“…Among the 8,056 studies, 290 passed the screening based on title and abstract among which 27 studies were selected for systematic review and meta-analysis ( Amornsupak et al, 2017 ; Ariga et al, 2001 ; Busch et al, 2012 ; Cai et al, 2017 ; Egeland et al., 2017 ; Eiro et al, 2019 ; Eiró et al., 2015 ; Gonzalez et al, 2009 ; Jung, Lee & Koo, 2015 ; Kim, Lee & Koo, 2016 ; Martinez et al, 2015 ; Min et al, 2013 ; Muchlińska et al., 2022 ; Park, Jung & Koo, 2016 ; Park, Kim & Koo, 2015 ; Paulsson et al, 2009 ; Pula et al, 2011 ; Pula et al, 2013a ; Pula et al, 2013b ; Schoppmann et al, 2012 ; Strell et al, 2019 ; Surowiak et al, 2007 ; Tanaka et al, 2021 ; Yamashita et al, 2012 ; Yang et al, 2017 ; Zhang et al, 2008 ; Zhou et al, 2018 ) ( Fig. 1 ).…”