title: Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets.
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.
authors.affiliation: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.|Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyashita
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Shuko
authors.initials: S
authors.lastname: Hata
authors.affiliation: Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Breast Surgery, Sagara Hospital, Social Medical Corporation Hakuaikai, 3-31 Matsubara-cho, Kagoshima, 892-0833, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Rai
authors.affiliation: Department of Breast Surgery, Sagara Hospital, Social Medical Corporation Hakuaikai, 3-31 Matsubara-cho, Kagoshima, 892-0833, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Sagara
authors.affiliation: Department of Pathology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Ohi
authors.affiliation: Department of Breast Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho, Aoba-ku, Sendai, 980-0803, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirakawa
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tamaki
authors.affiliation: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.affiliation: Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. hsasano@patholo2.med.tohoku.ac.jp.|Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. hsasano@patholo2.med.tohoku.ac.jp.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D018797:Cell Cycle Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D000199:Actins; D043925:Angiogenesis Inducing Agents; D018952:Antigens, CD34; D015415:Biomarkers; D018797:Cell Cycle Proteins; D064231:Nestin; C493181:VASH1 protein, human; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Cancer-associated fibroblasts; Insulin-like growth factor-1; Invasive lobular carcinoma; Microvessel density; Nestin; Vasohibin-1 positive ratio