nach oben

Erschienen in:

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

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

Erschienen in: Breast Cancer | Ausgabe 2/2012

Einloggen, um Zugang zu erhalten

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.

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

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

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

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

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, 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

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

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

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.

De Wever O, Mareel M. Role of tissue stroma in cancer cell invasion. J Pathol. 2003;200:429–47.PubMedCrossRef

11.

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.

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.

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.

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.

De Wever O, Demetter P, Mareel M. Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer. 2008;123:2229–38.PubMedCrossRef

16.

Mahadevan D, Von Hoff DD. Tumor–stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther. 2007;6:1186–97.PubMedCrossRef

17.

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.

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.

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.

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.

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.

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

Titel: Role of stromal myofibroblasts in invasive breast cancer: stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome
verfasst von: Masako Yamashita
Tomoko Ogawa
Xinhui Zhang
Noriko Hanamura
Yumi Kashikura
Mitsuyuki Takamura
Misao Yoneda
Taizo Shiraishi
Publikationsdatum: 01.04.2012
Verlag: Springer Japan
Erschienen in: Breast Cancer / Ausgabe 2/2012
Print ISSN: 1340-6868
Elektronische ISSN: 1880-4233
DOI: https://doi.org/10.1007/s12282-010-0234-5

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

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