title: Role of Wnt signaling pathway in progression of sinonasal inverted papilloma to squamous cell carcinoma.
abstract: BACKGROUND
  Sinonasal inverted papilloma (IP) is one of the most common benign tumors of the sinonasal area and malignant transformation has frequently been reported. However, the exact mechanism of the transition from benign lesion to malignancy is not known. The Wnt signaling pathway involves a network of multiple signaling glycoproteins that are known to play an important role in embryogenesis and carcinogenesis.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the role of the Wnt pathway and signaling proteins in malignant transformation of IP to dysplasia and squamous cell carcinoma.
  
  
  METHODS
  Expression of the Wnt signaling pathway proteins, including Wnt-1, beta-catenin, cyclin D1, and Dishevelled-1 (Dvl-1), were detected by immunohistochemistry by using 3-mm tissue core microarrays that consisted of 115 cores of IP tissue. Each of the IP cores was graded as I (prominent squamous metaplasia), II (inverted pattern), III (dysplasia), or IV (squamous cell carcinoma). The expression pattern of each protein and the correlation between the expression of each target protein and IP grade were evaluated.
  
  
  RESULTS
  Membranous staining of beta-catenin showed a significant positive correlation with IP grade (ρ = 0.247, p < 0.001), as did staining of cyclin D1 (ρ = 0.365, p < 0.001), which showed a nuclear pattern and staining of Dvl-1 (ρ = 0.380, p < 0.001), which showed a membranous, cytoplasmic, and nuclear pattern. For Dvl-1, a nuclear expression pattern was more frequently observed in grade III and IV IP (p = 0.036). In the case of Wnt-1, cytoplasmic expression was observed; however, it did not show a significant correlation with IP grade (ρ = 0.141, p = 0.130).
  
  
  CONCLUSIONS
  Wnt signaling proteins, including beta-catenin, cyclin D1, and Dvl-1, may play crucial roles in the malignant transformation of IP.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon-Si, Republic of Korea.
authors.forename: Yong Gi
authors.initials: YG
authors.lastname: Jung
authors.forename: Hyun Wook
authors.initials: HW
authors.lastname: Lee
authors.forename: Myung-Gu
authors.initials: MG
authors.lastname: Kim
authors.forename: Hun-Jong
authors.initials: HJ
authors.lastname: Dhong
authors.forename: Kyu-Sup
authors.initials: KS
authors.lastname: Cho
authors.forename: Hwan-Jung
authors.initials: HJ
authors.lastname: Roh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000503:physiopathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D018450:Disease Progression; D000072261:Dishevelled Proteins; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009669:Nose Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D018308:Papilloma, Inverted / Q000473:pathology* / Q000503:physiopathology*; D010255:Paranasal Sinus Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D010750:Phosphoproteins / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051155:Wnt1 Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606578:DVL1 protein, human; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D051155:Wnt1 Protein; D051176:beta Catenin; D019938:Cyclin D1