title: An immunohistochemical study of p53 and PCNA in inflammatory papillary hyperplasia of the palate: a dilemma of interpretation.
abstract: OBJECTIVE
  Inflammatory papillary hyperplasia of the palate (IPHP) or the granular type of denture stomatitis, is a non-neoplastic lesion characterized histologically by a significant epithelial hyperplasia and inflammatory infiltrate usually caused by trauma and Candida infection. p53 and proliferative cell nuclear antigen (PCNA) are cell-cycle regulators, that when overexpressed, are considered by many investigators as markers of malignant transformation. The objective of this study was to investigate the immunodetection of p53 and PCNA in IPHP, and to correlate these results with the degree of epithelial hyperplasia and inflammatory infiltrate.
  
  
  METHODS
  In 12 cases diagnosed clinically as IPHP, Candida was cultured from the denture base and the palatal mucosa. Lesions were biopsied and stained with H&E for histomorphometric analysis of the epithelial width and inflammatory infiltrate. PAS and Gram stains were used for screening of Candida. Sections were immunostained with DO-7 for p53 and PC-10 for PCNA. Fifteen palatal biopsies obtained from autopsies of edentulous subjects with normal palatal mucosa served as controls.
  
  
  RESULTS
  All cultures of swabs from both the palatal mucosa and denture base were positive for Candida. Candidal hyphae could not be identified in PAS stained sections. Small foci of Gram-positive organisms were found in two cases of IPHP. Epithelial width and inflammation were significantly higher in IPHP than in controls (P < 0.001). A three-fold increase in positively stained cells for p53 and a two-fold increase in positively stained cells for PCNA were seen in IPHP compared with controls (P < 0.001).
  
  
  CONCLUSIONS
  Although a significant increase in the immunodetection of p53 and PCNA may indicate a malignant potential, IPHP has never been reported to undergo malignant transformation nor is it associated with cytologic signs of dysplasia. The increase in the epithelial width and inflammation degree is probably associated with the colonization of the denture bases with Candida organisms. The increased detection of p53 and PCNA can be a secondary effect of cytokines originating from both the inflammatory cells and the keratinocytes. Thus, immunodetection of p53 and PCNA by current immunohistochemical methods on archival tissues is neither specific nor sensitive enough to be used as indicators for malignant potential in the absence of cytological dysplastic changes or genetic proof of mutated cell cycle genes.
authors.affiliation: Department of Oral Pathology and Oral Medicine, Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Kaplan
authors.forename: M
authors.initials: M
authors.lastname: Vered
authors.forename: D
authors.initials: D
authors.lastname: Moskona
authors.forename: A
authors.initials: A
authors.lastname: Buchner
authors.forename: D
authors.initials: D
authors.lastname: Dayan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002175:Candida / Q000302:isolation & purification; D002471:Cell Transformation, Neoplastic; D003827:Denture, Complete, Upper / Q000009:adverse effects; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry / Q000382:microbiology / Q000473:pathology*; D009062:Mouth Neoplasms / Q000175:diagnosis; D010159:Palate / Q000737:chemistry / Q000382:microbiology / Q000473:pathology*; D011230:Precancerous Conditions / Q000175:diagnosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D012680:Sensitivity and Specificity; D013282:Stomatitis, Denture / Q000209:etiology / Q000382:microbiology / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*