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Published in: Breast Cancer 2/2012

01-04-2012 | Original Article

Role of stromal myofibroblasts in invasive breast cancer: stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome

Authors: Masako Yamashita, Tomoko Ogawa, Xinhui Zhang, Noriko Hanamura, Yumi Kashikura, Mitsuyuki Takamura, Misao Yoneda, Taizo Shiraishi

Published in: Breast Cancer | Issue 2/2012

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Abstract

Background

Recently, the desmoplastic reaction has been implicated as having an important function in epithelial solid tumor biology. There have been no reports showing the relativity of invasive breast cancer and the desmoplastic reaction by a quantitative analysis of the myofibroblasts that were an important player in the desmoplastic reaction. The purpose of this study was to immunohistochemically investigate the correlation between the desmoplastic reaction and the clinicopathology of invasive breast cancer.

Methods

The study included 60 patients with a known prognosis of invasive breast cancer. We quantified the expression of α-SMA as a marker of myofibroblasts in the invasive breast cancer. After staining samples for α-SMA, their expression was extracted and quantified as a relative percentage by computer-assisted image analysis.

Results

There was relatively wide variation in the expression of α-SMA with the percentage of the area from 0.68 to 28.15% (mean 8.48 ± 5.40%). The metastasis group showed significantly higher α-SMA expression compared with the no metastasis group (p < 0.001). When the patients were divided into two groups according to their α-SMA expression using a cutoff point at the mean value of 8.48%, the high α-SMA group had a significantly poorer overall survival rate (p < 0.001). Multivariate analysis demonstrated that α-SMA and lymph node metastasis were identified as independent predictive factors of metastasis.

Conclusion

Myofibroblasts represent an important prognostic factor for invasive growth that is translated into a poor clinical prognosis for patients with invasive breast cancer.
Literature
1.
go back to reference van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.PubMedCrossRef van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.PubMedCrossRef
2.
go back to reference Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumors. Nature. 2000;406:747–52.PubMedCrossRef Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumors. Nature. 2000;406:747–52.PubMedCrossRef
3.
go back to reference van‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–6.CrossRef van‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–6.CrossRef
4.
go back to reference Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedCrossRef Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedCrossRef
5.
go back to reference Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, et al. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol. 2004;2:206–14.CrossRef Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, et al. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol. 2004;2:206–14.CrossRef
6.
go back to reference Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sørlie T, et al. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci USA. 2005;102:3738–43.PubMedCrossRef Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sørlie T, et al. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci USA. 2005;102:3738–43.PubMedCrossRef
7.
go back to reference Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650–9.PubMedCrossRef Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650–9.PubMedCrossRef
8.
go back to reference Mishra PJ, Mishra PJ, Humeniuk R, Medina DJ, Alexe G, Mesirov JP, et al. Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res. 2008;68:4331–9.PubMedCrossRef Mishra PJ, Mishra PJ, Humeniuk R, Medina DJ, Alexe G, Mesirov JP, et al. Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res. 2008;68:4331–9.PubMedCrossRef
9.
go back to reference Desmouliere A, Guyot C, Gabbiani G. The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int J Dev Biol. 2004;48:509–17.PubMedCrossRef Desmouliere A, Guyot C, Gabbiani G. The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int J Dev Biol. 2004;48:509–17.PubMedCrossRef
10.
11.
go back to reference Barsky SH, Green WR, Grotendorst GR, Liotta LA. Desmoplastic breast carcinoma as a source of human myofibroblasts. Am J Pathol. 1984;115:329–33.PubMed Barsky SH, Green WR, Grotendorst GR, Liotta LA. Desmoplastic breast carcinoma as a source of human myofibroblasts. Am J Pathol. 1984;115:329–33.PubMed
12.
go back to reference Yen TW, Aardal NP, Bronner MP, Thorning DR, Savard CE, Lee SP, et al. Myofibroblasts are responsible for the desmoplastic reaction surrounding human pancreatic carcinomas. Surgery. 2002;131:129–34.PubMedCrossRef Yen TW, Aardal NP, Bronner MP, Thorning DR, Savard CE, Lee SP, et al. Myofibroblasts are responsible for the desmoplastic reaction surrounding human pancreatic carcinomas. Surgery. 2002;131:129–34.PubMedCrossRef
13.
go back to reference Yamamoto H, Kondo M, Nakamori S, Nagano H, Wakasa K, Sugita Y, et al. JTE-522, a cyclooxygenase-2 inhibitor, is an effective chemopreventive agent against rat experimental liver fibrosis. Gastroenterology. 2003;125:556–71.PubMedCrossRef Yamamoto H, Kondo M, Nakamori S, Nagano H, Wakasa K, Sugita Y, et al. JTE-522, a cyclooxygenase-2 inhibitor, is an effective chemopreventive agent against rat experimental liver fibrosis. Gastroenterology. 2003;125:556–71.PubMedCrossRef
14.
go back to reference Sugimoto H, Mundel TM, Kieran MW, Kalluri R. Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther. 2006;5:1640–6.PubMedCrossRef Sugimoto H, Mundel TM, Kieran MW, Kalluri R. Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther. 2006;5:1640–6.PubMedCrossRef
15.
go back to reference De Wever O, Demetter P, Mareel M. Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer. 2008;123:2229–38.PubMedCrossRef De Wever O, Demetter P, Mareel M. Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer. 2008;123:2229–38.PubMedCrossRef
16.
go back to reference Mahadevan D, Von Hoff DD. Tumor–stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther. 2007;6:1186–97.PubMedCrossRef Mahadevan D, Von Hoff DD. Tumor–stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther. 2007;6:1186–97.PubMedCrossRef
17.
go back to reference Matubara D, Morikawa T, Goto A, Nakajima J, Fukayama M, Niki T. Subepithelial myofibroblast in lung adenomarcinoma: a histological indicator of excellent prognosis. Mod Pathol. 2009;22:776–85. Matubara D, Morikawa T, Goto A, Nakajima J, Fukayama M, Niki T. Subepithelial myofibroblast in lung adenomarcinoma: a histological indicator of excellent prognosis. Mod Pathol. 2009;22:776–85.
18.
go back to reference Kawashiri S, Tanaka A, Noguchi N, Hase T, Nakaya H, Ohara T, et al. Significance of stromal desmoplasia and myofibroblast appearance at the invasive front in squamous cell carcinoma of the oral cavity. Otorhinolaryngology. 2009;31:1346–53. Kawashiri S, Tanaka A, Noguchi N, Hase T, Nakaya H, Ohara T, et al. Significance of stromal desmoplasia and myofibroblast appearance at the invasive front in squamous cell carcinoma of the oral cavity. Otorhinolaryngology. 2009;31:1346–53.
19.
go back to reference Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 1999;59:5002–11.PubMed Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 1999;59:5002–11.PubMed
20.
go back to reference Tsujino T, Seshimo I, Yamamoto H, Ngan CY, Ezumi K, Takemasa I, et al. Stromal myofibroblasts predict disease recurrence for corectal cancer. Clin Cancer Res. 2007;13:2082–90.PubMedCrossRef Tsujino T, Seshimo I, Yamamoto H, Ngan CY, Ezumi K, Takemasa I, et al. Stromal myofibroblasts predict disease recurrence for corectal cancer. Clin Cancer Res. 2007;13:2082–90.PubMedCrossRef
21.
go back to reference Hasebe T, Sasaki S, Imoto S, Ochiai A. Proliferative activity of intratumoral fibroblasts is closely correlated with lymph node and distant organ metastasis of invasive ductal carcinoma of the breast. Am J Pathol. 2000;156:1701–10.PubMedCrossRef Hasebe T, Sasaki S, Imoto S, Ochiai A. Proliferative activity of intratumoral fibroblasts is closely correlated with lymph node and distant organ metastasis of invasive ductal carcinoma of the breast. Am J Pathol. 2000;156:1701–10.PubMedCrossRef
22.
go back to reference Yazhou C, Wenlv S, Weidong Z, Licun W. Clinicopathological significance of stromal myofibroblasts in invasive ductal carcinoma of the breast. Tumor Biol. 2004;25:290–5.CrossRef Yazhou C, Wenlv S, Weidong Z, Licun W. Clinicopathological significance of stromal myofibroblasts in invasive ductal carcinoma of the breast. Tumor Biol. 2004;25:290–5.CrossRef
Metadata
Title
Role of stromal myofibroblasts in invasive breast cancer: stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome
Authors
Masako Yamashita
Tomoko Ogawa
Xinhui Zhang
Noriko Hanamura
Yumi Kashikura
Mitsuyuki Takamura
Misao Yoneda
Taizo Shiraishi
Publication date
01-04-2012
Publisher
Springer Japan
Published in
Breast Cancer / Issue 2/2012
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-010-0234-5

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