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Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets

Breast Cancer Research and Treatment volume 155, pages 65–75 (2016)Cite this article

Abstract

Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC.

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Acknowledgments

This work was partly supported by Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (Tokyo, Japan).

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Affiliations

  1. Department of Surgical Oncology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Saki Nakagawa, Minoru Miyashita, Takanori Ishida & Noriaki Ohuchi

  2. Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan

    Saki Nakagawa, Yayoi Takahashi, Mika Watanabe & Hironobu Sasano

  3. Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan

    Yasuhiro Miki, Shuko Hata, Kentaro Tamaki, Takashi Suzuki & Hironobu Sasano

  4. Department of Breast Surgery, Sagara Hospital, Social Medical Corporation Hakuaikai, 3-31 Matsubara-cho, Kagoshima, 892-0833, Japan

    Yoshiaki Rai & Yasuaki Sagara

  5. Department of Pathology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan

    Yasuyo Ohi

  6. Department of Breast Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho, Aoba-ku, Sendai, 980-0803, Japan

    Hisashi Hirakawa

Authors
  1. Saki Nakagawa
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  2. Yasuhiro Miki
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  3. Minoru Miyashita
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Correspondence to Hironobu Sasano.

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Nakagawa, S., Miki, Y., Miyashita, M. et al. Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets. Breast Cancer Res Treat 155, 65–75 (2016). https://doi.org/10.1007/s10549-015-3668-9

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Keywords

  • Invasive lobular carcinoma
  • Cancer-associated fibroblasts
  • Microvessel density
  • Vasohibin-1 positive ratio
  • Nestin
  • Insulin-like growth factor-1