title: Expression of the p53 homologue p63 in early cervical neoplasia.
abstract: BACKGROUND
  p63, a homologue of the tumor suppressor gene p53, is expressed in embryonic, adult murine, and human basal squamous epithelium and encodes both transactivating and dominant negative transcript isoforms. Mouse embryos functionally deficient in p63 fail to replenish basal squamous epithelial cells, resulting in multiple defects that include absent genital squamous epithelium. This study investigated the expression of p63 in the human cervical transformation zone and early cervical neoplasia.
  
  
  METHODS
  Tissue localization of p63 was determined by immunohistochemistry in a wide range of epithelia. A correlation was also made between p63 expression and squamous basal cell (keratin 14), endocervical columnar cell (mucicarmine), and cell-cycle specific (Ki-67) markers.
  
  
  RESULTS
  p63 expression by immunostaining delineated basal and parabasal cells of maturing ectocervical squamous mucosa, squamous metaplasia in the cervix, and basal and subcolumnar cells of the cervical transformation zone. In atrophic epithelia immunostaining for p63 was present in all cell strata. In early cervical neoplasia, p63 expression was inversely correlated with both squamous cell maturation and nonsquamous differentiation in CIN. This biomarker also identified basal cells in a subset of preinvasive cervical neoplasms with endocervical cell differentiation that were bcl-2 and keratin 14 negative.
  
  
  CONCLUSIONS
  In the lower female genital tract, p63 is preferentially expressed in immature cells of squamous lineage and is not linked to cell proliferation. The broader range of p63 expression relevant to keratin 14 and bcl-2 indicates that p63 may identify additional subsets of benign and neoplastic epithelial basal cells in the cervical transformation zone and may be useful in studying cell differentiation in the early stages of neoplastic change in this region.
authors.affiliation: Division of Women's and Perinatal Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Quade
authors.forename: A
authors.initials: A
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.forename: E E
authors.initials: EE
authors.lastname: Sheets
authors.forename: A
authors.initials: A
authors.lastname: Cviko
authors.forename: J M
authors.initials: JM
authors.lastname: Federschneider
authors.forename: R
authors.initials: R
authors.lastname: Peters
authors.forename: F D
authors.initials: FD
authors.lastname: McKeon
authors.forename: C P
authors.initials: CP
authors.lastname: Crum
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D001284:Atrophy / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D053547:Keratin-14; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; C507540:KRT14 protein, human; D053547:Keratin-14; D019394:Ki-67 Antigen; C507446:Krt14 protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D025521:Tumor Suppressor Proteins; D007633:Keratins