title: The associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  Maspin, a member of the serpin family, is a suppressor of tumor growth, an inhibitor of angiogenesis and an inducer of apoptosis. Maspin induces apoptosis by increasing Bax, a member of the Bcl-2 family of apoptosis-regulating proteins. In this exploratory study, we investigated the associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma (IHCCA).
  
  
  METHODS
  Twenty-two paraffin-embedded samples were analyzed by immunohistochemical methods using Maspin, Bax and CD34 antibodies. Maspin was scored semiquantitatively (HSCORE). Apoptosis was assessed using an antibody against cleaved caspase-3.
  
  
  RESULTS
  The strong relationship observed between the expression of Maspin and Bax, indicates that Bax is likely to be the key effector of Maspin-mediated induction of apoptosis as indicated by the activation of cleaved caspase-3. We categorized Maspin HSCORE by calculating the optimal cutpoint. A Maspin HSCORE above the cutpoint was inversely related with tumor dimension, depth of tumor and vascular invasion. Uni/multivariate analysis suggests that a Maspin HSCORE below the cutpoint significantly worsens the patients' prognosis. Tumors with Maspin HSCORE below the cutpoint had a shorter survival (11+/-5 months) than did patients with Maspin HSCORE above the cutpoint (27+/-4 months), whereas Kaplan-Meier analysis and logrank test showed no significant difference in overall survival between the patients.
  
  
  CONCLUSIONS
  The associated expression of Maspin and Bax might delay tumor progression in IHCCA. Maspin above the cutpoint might counteract tumor development by increasing cell apoptosis, and by decreasing tumor mass and cell invasion. The combined expression of Maspin and Bax appears to influence the susceptibility of tumor cholangiocytes to apoptosis and thus may be involved in delaying IHCCA progression.
authors.affiliation: Dipartimento di Medicina Sperimentale--Sezione di Patologia Molecolare ed Immunologia, Università degli Studi di Parma, 43100 Parma, Italy. antonello.romani@studenti.unipr.it <antonello.romani@studenti.unipr.it>
authors.forename: Antonello A
authors.initials: AA
authors.lastname: Romani
authors.forename: Paolo
authors.initials: P
authors.lastname: Soliani
authors.forename: Silvia
authors.initials: S
authors.lastname: Desenzani
authors.forename: Angelo F
authors.initials: AF
authors.lastname: Borghetti
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Crafa
mesh_terms: D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D015843:Serpins / Q000096:biosynthesis* / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
chemical_list: C494826:BAX protein, human; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C085344:SERPIN-B5; D015843:Serpins; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3