title: Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors.
abstract: BACKGROUND
  Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples.
  
  
  METHODS
  Primary and metastatic colorectal tumor tissues (1-2 mm(3)) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts.
  
  
  RESULTS
  From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate = 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 ± 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor.
  
  
  CONCLUSIONS
  Xenograft animal models derived from fresh surgical sample maintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers.
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Yong Beom
authors: YB
authors: Cho
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Hye Kyung
authors: HK
authors: Hong
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Yoon-La
authors: YL
authors: Choi
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Ensel
authors: E
authors: Oh
authors: Department of Anatomy and Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Kyeung Min
authors: KM
authors: Joo
authors: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Juyoun
authors: J
authors: Jin
authors: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Do-Hyun
authors: DH
authors: Nam
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Young-Hyeh
authors: YH
authors: Ko
authors: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: lwy555@skku.edu.
authors: Woo Yong
authors: WY
authors: Lee
mesh_terms: D000368:Aged; D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts / Q000473:pathology*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome; D014183:Transplantation, Heterologous / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
keywords: Colorectal cancer; Liver metastasis; Xenograft