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Review
. 2012 Dec;7(6):477-83.
doi: 10.1159/000345464.

Overexpression of caveolin-1 in cancer-associated fibroblasts predicts good outcome in breast cancer

Wang Shan-Wei  1 , Xu Kan-Lun  2 , Ruan Shu-Qin  3 , Zhao Li-Li  3 , Chen Li-Rong  2
Affiliations
Review

Overexpression of caveolin-1 in cancer-associated fibroblasts predicts good outcome in breast cancer

Wang Shan-Wei et al. Breast Care (Basel). 2012 Dec.

Abstract
in English, German

Background: The aim of this study was to investigate the expression of caveolin-1 (Cav-1) in cancer-associated fibroblasts (CAFs) and to explore its correlation with clinicopathologic parameters and prognosis.

Materials and methods: Cav-1 expression was detected in the stroma of 143 patients with breast cancer, 10 patients with ductal carcinoma in situ (DCIS), and 10 normal breast tissue samples.

Results: Overexpression of stromal Cav-1 in breast cancer was associated with histological type, low histological grade, estrogen receptor (ER) negativity, and molecular subtypes. The expression rate of stromal Cav-1 in breast cancer (65.7%, 94/143) was significantly higher than that of DCIS (0%, 0/10) and normal breast tissue (0%, 0/10) (p = 0.000). A positive correlation was found between stromal Cav-1 and ER (p = 0.046, rs = 0.218). Stromal Cav-1 expression in luminal B was significantly higher than in basal-like type (p = 0.048). Furthermore, stromal expression of Cav-1 was significantly correlated with the 5-year survival rate (p = 0.029), and it was an independent prognostic factor (p = 0.009).

Conclusion: Cav-1 expression in CAFs was correlated with histological type, histological grade, ER status, and molecular subtypes in breast cancer. Stromal Cav-1 expression was an independent prognostic factor, and the absence or reduction of Cav-1 expression in stromal CAFs of invasive breast cancer predicts poor prognostic outcome.

Hintergrund: Ziel dieser Studie war es, die Expression von Caveolin-1 (Cav-1) in karzinomassoziierten Fibroblasten (CAFs) und ihre Korrelation mit klinisch-pathologischen Parametern und Prognose zu untersuchen.

Material und methoden: Die Cav-1-Expression wurde im Stroma von 143 Mammakarzinompatientinnen, 10 Patientinnen mit duktalem Carcinoma in situ (DCIS) und 10 normalen Brustgewebeproben bestimmt.

Ergebnisse: Überexpression von Cav-1 im Stroma von Mammakarzinomen war mit dem histologischen Typ, einem niedrigen histologischen Grad, Östrogenrezeptor (ER)-Negativität und molekularem Subtyp assoziiert. Die Expressionsrate von stromalem Cav-1 beim Mammakarzinom (65,7%, 94/143) war signifikant höher als beim DCIS (0%, 0/10) und im normalen Brustgewebe (0%, 0/10) (p = 0,000). Zwischen stromalem Cav-1 und ER bestand eine positive Korrelation (p = 0,046, rs = 0,218). Die Expression von stromalem Cav-1 im Luminal-B-Subtyp war signifikant höher als im Basal-like-Subtyp (p = 0,048). Desweiteren war die stromale Expression von Cav-1 signifikant mit dem 5-Jahresüberleben korreliert (p = 0,029) und wurde als ein unabhängiger Prognosefaktor identifiziert (p = 0,009).

Schlussfolgerung: Die Cav-1-Expression in CAFs beim Mammakarzinom war mit dem histologischen Typ und Grad, dem ER-Status sowie dem molekularen Subtyp korreliert. Die stromale Cav-1-Expression war ein unabhängiger Prognosefaktor, und fehlende bzw. reduzierte Cav-1-Expression in stromalen CAFs beim invasiven Mammakarzinom ist indikativ für ein schlechtes Outcome.

Keywords: Biomarker; Breast cancer; Cancer-associated fibroblasts; Gene; Prognosis.

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Figures

Fig. 1
Fig. 1
Stromal caveolin-1 (Cav-1) expression in human breast cancers and normal breast tissue. A The mammary intralobular stroma, vasculature, and myoepithelial cells are normally Cav-l-positive. B Cav-1 expression in the stroma of ductal carcinoma in situ; myoepithelial cells are Cav-l-positive. C Cav-1 expression in the stroma of invasive ductal carcinoma. D Absence of Cav-1 in neoplastic stroma. E Cav-1 expression in the stroma of invasive lobular carcinomas. F Weak expression of Cav-1 in the tumor epithelium of the basal-like subtype (EnVision, ×100).
Fig. 2
Fig. 2
Kaplan-Meier curves of 5-year survival in 143 breast cancer patients.
Fig. 3
Fig. 3
Kaplan-Meier curves of 5-years survival in 105 invasive ductal carcinoma (IDC) patients. Note that a low level of stromal Cav-1 immunostaining also predicts poor clinical outcome in IDC patients (p = 7.97; ×10−3, log-rank test).
Fig. 4
Fig. 4
Kaplan-Meier curves of 5-years survival in 38 patients with N1 lymph node status.
Fig. 5
Fig. 5
Kaplan-Meier curves of 5-years survival in 66 estrogen receptor-positive patients.
Fig. 6
Fig. 6
Kaplan-Meier curves of 5-years survival in 22 TNM stage I patients.
See this image and copyright information in PMC

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