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RESEARCH PRODUCT

The associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma

Antonello A. RomaniPaolo SolianiSilvia DesenzaniPellegrino CrafaAngelo F. Borghetti

subject

MaleCancer ResearchPathologymedicine.medical_specialtyAngiogenesisApoptosisCaspase 3Kaplan-Meier EstimateSerpinlcsh:RC254-282law.inventionCholangiocarcinomaBcl-2-associated X proteinlawBiomarkers TumorGeneticsmedicineHumansGenes Tumor SuppressorSerpinsIntrahepatic CholangiocarcinomaAgedbcl-2-Associated X ProteinbiologyCaspase 3business.industryMicrocirculationLiver NeoplasmsMaspinMiddle AgedPrognosislcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensNeoplasm ProteinsEnzyme ActivationOncologyApoptosisCancer researchbiology.proteinSuppressorFemalebusinessResearch Article

description

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. Conclusion 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.

yearjournalcountryeditionlanguage
2006-10-26BMC Cancer
https://doi.org/10.1186/1471-2407-6-255