title: Observations on tumor and metastatic suppressor gene status in endometrial carcinoma with particular emphasis on p53.
abstract: BACKGROUND
  Genetic changes in the development of endometrial carcinoma have not been characterized, and little is known of tumor or metastatic suppressor gene status in these malignancies. The current study on endometrioid carcinoma was undertaken to examine the status of two tumor suppressor genes that frequently have been found to be altered in human malignancies (the p53 gene and the retinoblastoma [Rb] gene) and to examine the status of the candidate metastatic suppressor gene, nm23-H1.
  
  
  METHODS
  The status of the p53 gene was studied by immunohistochemistry of formalin-fixed paraffin-embedded biopsy samples from 72 patients with atypical endometrial hyperplasia or endometrioid carcinoma who underwent hysterectomy immediately after biopsy and from 5 patients with benign endometria. A search for loss of heterozygosity (LOH) of the nm23 gene after DNA extraction from frozen tissues and hybridization with nm23-H1 cDNA specific probe was made in 10 endometrial carcinomas. Rb gene status was evaluated by image analysis quantification of immunoreactive retinoblastoma protein in frozen sections of 10 carcinomas and 2 benign endometria.
  
  
  RESULTS
  p53 expression was low in all benign endometria, but high expression was found in 2 (15%) of 13 atypical hyperplasias and in 23 (39%) of 59 carcinomas. High levels of p53 expression in endometrioid carcinoma correlated with the spread of disease outside of the uterus and by logistic regression, the presence of squamous differentiation, nuclear grade, and high p53 expression in the biopsy all independently correlated with spread of disease outside of the uterus. Although 7 of the 10 carcinomas studied were informative, LOH for the nm23 gene was not seen in any, including a site of metastasis. Rb protein expression in endometrial carcinoma was similar to expression in benign endometria.
  
  
  CONCLUSIONS
  Although this study found no evidence of nm23-H1 gene alteration or alterations in Rb protein levels in endometrial carcinoma, high expression of p53 protein was sporadically identified in biopsy specimens of atypical hyperplasia and frequently found in endometrioid carcinomas. Determination of p53 expression in combination with the presence or absence of squamous differentiation and nuclear grade in biopsy material may help predict spread of endometrioid carcinoma outside the uterus and facilitate therapeutic planning before hysterectomy.
authors.affiliation: Department of Pathology, Albany Medical College, NY 12208.
authors.forename: R A
authors.initials: RA
authors.lastname: Ambros
authors.forename: P A
authors.initials: PA
authors.lastname: Vigna
authors.forename: J
authors.initials: J
authors.lastname: Figge
authors.forename: B V
authors.initials: BV
authors.lastname: Kallakury
authors.forename: A
authors.initials: A
authors.lastname: Mastrangelo
authors.forename: A Y
authors.initials: AY
authors.lastname: Eastman
authors.forename: J
authors.initials: J
authors.lastname: Malfetano
authors.forename: H L
authors.initials: HL
authors.lastname: Figge
authors.forename: J S
authors.initials: JS
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D002467:Cell Nucleus / Q000648:ultrastructure; D004714:Endometrial Hyperplasia / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma / Q000235:genetics*; D016153:Genes, Suppressor / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase; D016160:Retinoblastoma Protein / Q000032:analysis / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins