title: The clinical implication of cancer-associated microvasculature and fibroblast in advanced colorectal cancer patients with synchronous or metachronous metastases.
abstract: BACKGROUND
  We aimed to evaluate the clinical significance of microvessel density (MVD), lymphatic vessel density (LVD), and cancer-associated fibroblasts (CAFs) in relation to tumor location in advanced colorectal cancer (CRC).
  
  
  METHODS
  Using immunohistochemistry, we examined 181 advanced CRC patients for CD31 and D2-40 to measure MVD and LVD, respectively, α-smooth muscle actin (SMA) and desmin to identify CAFs, and PTEN to examine genetic changes of CAFs. To evaluate the regional heterogeneity of these properties, we examined tissue from four sites (the center and periphery of the primary cancer, a distant metastasis, and a lymph node metastasis) in each patient.
  
  
  RESULTS
  MVD, LVD, and CAFs showed significant heterogeneity with respect to the tumor location. LVD was the greatest in the center of the primary cancers and the amount of CAFs was the lowest in distant metastases. In distant metastases, those from the lung had higher LVD and MVD, but fewer CAFs than those from the liver, peritoneum, or ovary. Patients with low MVD and LVD in the center of the primary cancer had worse outcomes and patients with few CAFs in distant metastases and in the primary tumor had a lower survival rate. PTEN expression in CAFs in distant metastases was lost in 11 of 181 CRC patients (6.1%), which was associated with a worse prognosis.
  
  
  CONCLUSIONS
  The microenvironment, including cancer-associated microvasculature and fibroblasts, is heterogeneous with respect to the tumor location in CRC patients. Therefore, heterogeneity of microenvironments should be taken into account when managing CRC patients.
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yoonjin
authors.initials: Y
authors.lastname: Kwak
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Hee Eun
authors.initials: HE
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, South Korea.
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, South Korea.
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Kang
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, South Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D003893:Desmin / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000098:blood supply / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor; D003893:Desmin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human