title: Nucleus Accumbens-Associated Protein 1 Expression Has Potential as a Marker for Distinguishing Oral Epithelial Dysplasia and Squamous Cell Carcinoma.
abstract: BACKGROUND
  Oral epithelial dysplasia (OED) and carcinoma in situ (CIS) are defined by dysplastic cells in the epithelium. Over a third of oral squamous cell carcinoma (OSCC) patients present with associated OED. However, accurate histopathological diagnosis of such lesions is difficult. Nucleus accumbens-associated protein 1 (NAC1) is a member of the Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex family of proteins, and is overexpressed in OSCC. This study aimed to determine whether NAC1 has the potential to be used as a marker to distinguish OED and OSCC.
  
  
  RESULTS
  The study included 114 patients (64 men, 50 women). There were 67, 10, and 37 patients with OED, CIS, and OSCC, respectively. NAC1 labeling indices (LIs) and immunoreactivity intensities (IRI) were evaluated. The patients' pathological classification was significantly associated with age, sex, NAC1 LIs, and NAC1 IRI (p = 0.025, p = 0.022, p < 0.001, and p < 0.001, respectively). As a result of multivariate analysis, a predictive model was made; this identified the NAC1 LIs (OR [95% CI] 1.18 [1.11-1.28], p < 0.001) and NAC1 IRI (0.78 [0.68-0.86], p < 0.001) as predictive factors for CIS/OSCC. The NAC1 LIs/IRI cut-off values which discriminated between OED and CIS/OSCC were 50%/124 pixels. For NAC1 LIs with > 50% positivity the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.766, 0.910, 0.857, and 0.847, respectively. For NAC1 IRI with ≤ 124 positive pixels, the sensitivity, specificity, PPV, and NPV were 0.787, 0.866, 0.804, and 0.853, respectively. Though there are several potential limitations to this study and the results were obtained from a retrospective analysis of a single site cohort, the data suggest that the NAC1 LIs/IRI is a strong predictor of CIS/OSCC.
  
  
  CONCLUSIONS
  NAC1 has potential as a marker for distinguishing OED from CIS/OSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Sekine
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Hyogo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakatani
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohira
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Hideshima
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kanno
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nariai
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Hyogo, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kagimura
authors.affiliation: Department of Biochemistry, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism*; D003937:Diagnosis, Differential; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C516477:NACC1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins