title: Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  Smad4 is found mutated in many cancers. It acts as a tumor suppressor in the regulation of TGF-β signaling pathway. The objective of this work was to study the expression of Smad4 in intrahepatic cholangiocarcinoma (ICC) and its relationship with the biological behavior and prognosis of the disease.
  
  
  METHODS
  Forty-nine paraffin-embedded ICC specimens and nine normal liver tissues were analyzed by immunohistochemical methods using Smad4 monoclonal antibodies. The expression of Smad4 was compared with the clinical pathological characteristics of the patients.
  
  
  RESULTS
  The expression of Smad4 was 100% positive in normal liver tissues, which was higher than that in the ICC (44.9%). Negative labeling of the Smad4 protein was found in 26.1% (6/23) of well-differentiated ICCs and 61.5% (16/26) of poorly to moderately differentiated ICCs, and 34.3% (12/35) and 71.4% (10/14) showed negative Smad4 labeling (P = 0.018) of ICC at pathological Tumor Node Metastasis (pTNM) stage I-II and pTNM stage III-IV separately. Furthermore, 72% (8/11) of lymph node metastatic ICCs and 73.3% (11/15) of intrahepatic metastatic ICCs showed negative labeling of the Smad4 protein. The loss of Smad4 expression in those metastatic ICCs was significantly more severe compared with non-metastatic ICCs (P = 0.000).
  
  
  CONCLUSIONS
  The expression of Smad4 was associated with the histological grade, clinical stage, and metastasis of ICC (P < 0.05). The detection of Smad4 may be helpful in determining the degree of malignancy and prognosis of ICC.
authors: Wuhan Medical & Health Center For Women and Children, Wuhan, Hubei, China.
authors: Xue-qiang
authors: XQ
authors: Yan
authors: Wei
authors: W
authors: Zhang
authors: Bi-xiang
authors: BX
authors: Zhang
authors: Hui-fang
authors: HF
authors: Liang
authors: Wan-guang
authors: WG
authors: Zhang
authors: Xiao-ping
authors: XP
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction / Q000502:physiology; D051901:Smad4 Protein / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta