Expression And Clinical Significance Of Livin、FHIT And Mcm3in Sinonasal Inverted Papilloma

Background and ObjectiveInverted papilloma (IP) is a benign sinonasal epithelial tumor that has a knownpropensity for recurrence, local aggressiveness and an association with transformationto squamous cell carcinoma which makes it possess distinctive features from otherbenign sinonasal neoplasms. The etiology and causes for sinonasal inverted papilloma(SNIP) are complex which have yet to be fully elucidated.Its occurrence, recurrence,malignant pathological mechanisms are rarely reported, which may be the combinedresult of multi-factor, multi-stage, multi-gene. In recent years, with the rapiddevelopment of tumor molecular biology research, intervention-related apoptosis-inhibitingfactor has become a hot.A novel human inhibitor of apoptosis protein (IAP) family member termed Livinwas identified and it is an important anti-apoptotic protein which is different from theBcl-2family. This study found that it plays an important role in apoptosis and theoccurrence of head and neck cancer. FHIT is a new multiple tumor suppressor genewhich located in carcinogen sensitive chromosome fragile sites FRA3B. FHIT proteinnormally expresses in most normal tissues and plays a key role in the occurrence anddevelopment of tumors which is similar to other tumor suppressor gene such as p53,p16. Mcm3(minichromosome maintenance protein3) is an important subunit of theminichromosome maintenance protein family required for the initiation andelongation of DNA replication in eukaryotes. Mcm3is a novel and indispensableproliferation marker. This aim of the study was to analyze the expression and distribution of Livin,FHIT and Mcm3in SNIP, and explore their functions in the occurrence,development, recurrence, malignant transformation mechanisms of SNIP, providenew reference for biological characteristics, clinical diagnosis and treatment schemesfor SNIP.Materials and MethodsThis study was performed using formalin-fixed, paraffin embedded tissue blocksof SNIP and NSCC (sinonasal squamous cell carcinoma)which were collected fromthe Department of nose,the First Affiliated Hospital of Zhengzhou Universitybetween2011~2013. The numbers of experimental group respectively were32casesand20cases and the surgical excision, clinical data and follow-up records wereallintegrity. Meanwhile18cases of normal nasal mucosa taken from nose andanterior skull base benign tumor resection were selected as a control group (NM).Immunohistochemistry and Western Blot test were respectively used to observe theexpression of Livin, FHIT and Mcm3in each group.Results1．The expression of Livin increased in the SNIP and NSCC, the former is weakerthan the latter expression and the difference was statistically significant. Normal nasalmucosa occasionally saw Livin expression, the expression was weaker than that in theSNIP and NSCC, the difference was statistically significant (P<0.01).2．FHIT protein were mainly seen in the normal group, FHIT expression in SNIP wasweaker than normal nasal mucosa, the difference wasstatistically significant; NSCCoccasionally saw expression and the expression was weaker than that in SNIP andNM which was significant difference (P<0.01).3．The expression of Mcm3increased in the SNIP and NSCC, the former is weakerthan the latter expression and the difference was statistically significant. Normal nasalmucosa occasionally saw Livin expression, the expression was weaker than that in theSNIP and NSCC, and the difference was statistically significant (P<0.01).4．By Spearman’s correlation test, FHIT and Livin expression in SNIP was negativelycorrelated (P<0.01). There was no correlation between FHIT and Mcm3expression ofSNIP, and the same situation occurred between Mcm3and Livin expression (P>0.01). 5．In SNIP tissue, with its clinical stage increased, Livin expression increased and thedifference was statistically significant (P<0.01); however, it has nothing to do withage, pathological type and the recurrence (P>0.01). FHIT expression in older patientsof SNIP declined, the difference was statistically significant (P<0.01) and theexpression decreased with tumor recurrence, a statistically significant difference(P<0.01); FHIT expression has nothing to do with pathological type, clinical stage(P>0.01). Mcm3in recurrent inverted papilloma tissue was higher than that ofprimary tissue, the difference was statistically significant (P<0.01); Mcm3proteinexpression increased with the pathological type increased, the difference wasstatistically significant (P<0.01); however, it has nothing to do with age and clinicalstage.Conclusions1．The aetiology of SNIP is the combined result of multi-factor, multi-gene,multi-step, multi-stage. Livin upregulated, reduced FHIT expression and Mcm3raisedall play an important role in the pathogenesis of SNIP which means that inhibition ofapoptosis program, tumor suppressor gene deletion and cell cycle dysregulationleading to abnormal cell proliferation are important causes of SNIP.2．With clinical stage rises, Livin expression increases in SNIP tissue whichillustrates that it participates in the development and progression of SNIP.3．In SNIP tissue, FHIT expression increased with age and decreased with tumorrecurrence which shows it is easier to decreased expression of tumor suppressor genesand malignancy for older patients of SNIP relapsed.4．Expression of FHIT and Livin protein in SNIP tissue was negatively correlated,and there is a coordinating role in the pathogenesis.The combination of both can beused as potential targets for SNIP diagnosis and treatment.5．Mcm3increases with SNIP recurrence and the degree of malignancy which showsthat overexpression of Mcm3is involved in the recurrence and malignantof SNIPwhich can be used as a potential target for therapy, the recurrence and malignancymarkers,additionally an important indicator of assessment and detection of recurrenceand malignant.