Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets

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• 作者：Saki Nakagawa ; Yasuhiro Miki ; Minoru Miyashita…
• 关键词：Invasive lobular carcinoma ; Cancer ; associated fibroblasts ; Microvessel density ; Vasohibin ; 1 positive ratio ; Nestin ; Insulin ; like growth factor ; 1
• 刊名：Breast Cancer Research and Treatment
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：155
• 期：1
• 页码：65-75
• 全文大小：2,368 KB
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• 作者单位：Saki Nakagawa (1) (2)
  Yasuhiro Miki (3)
  Minoru Miyashita (1)
  Shuko Hata (3)
  Yayoi Takahashi (2)
  Yoshiaki Rai (4)
  Yasuaki Sagara (4)
  Yasuyo Ohi (5)
  Hisashi Hirakawa (6)
  Kentaro Tamaki (3)
  Takanori Ishida (1)
  Mika Watanabe (2)
  Takashi Suzuki (3)
  Noriaki Ohuchi (1)
  Hironobu Sasano (2) (3)
  
  1. Department of Surgical Oncology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan
  2. Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
  3. Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
  4. Department of Breast Surgery, Sagara Hospital, Social Medical Corporation Hakuaikai, 3-31 Matsubara-cho, Kagoshima, 892-0833, Japan
  5. Department of Pathology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan
  6. Department of Breast Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho, Aoba-ku, Sendai, 980-0803, Japan
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

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.