title: Concurrent endometrial intraepithelial carcinoma (EIC) and serous ovarian cancer: can EIC be seen as the precursor lesion?
abstract: OBJECTIVE
  The pathogenesis of serous ovarian carcinoma (SOC) is still unknown. Recently, endometrial intraepithelial carcinoma (EIC) was proposed to be the precursor lesion of SOC. This study examines the model of EIC as precursor for SOC.
  
  
  METHODS
  Cases of SOC with a noninvasive or superficially invasive serous lesion, a hyperplastic lesion with/without atypia, or EIC in the endometrium were selected for inclusion in this study. Tissue sections from both ovaries, the fallopian tubes, and the uterus were extensively reviewed by an expert gynecopathologist. For both EIC and SOC, immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor; TP53 mutation analysis; and in situ ploidy analysis were performed.
  
  
  RESULTS
  Nine cases of SOC with concurrent EIC in the endometrium were identified. Immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor revealed almost identical expression patterns and similar intensities in each pair of EIC and coincident SOC. Identical TP53 mutations were found in SOC and coinciding EIC in 33% of the cases, suggesting a clonal origin. DNA ploidy analysis, as a marker for neoplastic progression, demonstrated an increased number of aneuploid nuclei in SOC compared to their corresponding EIC (P = 0.039). In addition, the mean amount of DNA per nucleus in SOC was higher (ie, more aneuploid) compared to EIC (P = 0.039).
  
  
  CONCLUSIONS
  This study provides a first indication of EIC as possible precursor lesion for SOC. This finding could have major clinical implications for future ovarian cancer management and underscores EIC as a possible target for early SOC detection and prevention.
authors.affiliation: Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, The Netherlands. T.Roelofsen@obgyn.umcn.nl
authors.forename: Thijs
authors.initials: T
authors.lastname: Roelofsen
authors.forename: Léon C L T
authors.initials: LC
authors.lastname: van Kempen
authors.forename: Jeroen A W M
authors.initials: JA
authors.lastname: van der Laak
authors.forename: Maaike A
authors.initials: MA
authors.lastname: van Ham
authors.forename: Johan
authors.initials: J
authors.lastname: Bulten
authors.forename: Leon F A G
authors.initials: LF
authors.lastname: Massuger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011003:Ploidies; D011230:Precancerous Conditions / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*