title: Morphological and immunohistochemical pattern of tubo-ovarian dysplasia and serous tubal intraepithelial carcinoma.
abstract: OBJECTIVE
  Histopathological examination of material from prophylactic salpingo-oophorectomies performed in patients at genetic risk of ovarian cancer can reveal abnormalities interpreted as possible pre-cancerous "ovarian dysplasia" and tubal precursors lesions. We sought to study the morphological features and immunohistochemical expression patterns of neoplasia-associated markers in prophylactically removed ovaries and fallopian tubes (pBSO) in comparison with a group of serous tubal intraepithelial carcinoma (STIC) and non-cancerous controls.
  
  
  METHODS
  Morphological features and immunohistochemical expression patterns of Ki-67 (for proliferation biomarker), p53 (key pathway of mullerian serous tumorogenesis), Bcl2 (anti-apoptotic), γH2AX (a double-strand breaks marker) and ALDH1 (a stem cell marker significantly associated with early-stage ovarian cancer) were blindly evaluated by two pathologists in 111 pBSO, 12 STICs and 116 non-cancerous salpingo-oophorectomies (control group) (nBSO).
  
  
  RESULTS
  Morphological ovarian and tubal dysplasia scores were significantly higher in the pBSO than in controls (respectively, 8.8 vs 3.12, p<0.0001, for ovaries and 6.54 vs 1.58, p<0.0001 for tubes). Increased γH2AX expression was observed in the pBSO and STICs compared with the controls whereas expression patterns of Ki67, p53 and bcl2 were low to moderate in the pBSO group. STICs overexpressed Ki67 and p53 while bcl2 expression was low; Interestingly, ALDH1 expression was low in non dysplastic epithelium, high in dysplasia and constantly low in STICs.
  
  
  CONCLUSIONS
  The morphological and immunohistochemical profile of tubo-ovarian dysplasia and STICs might be consistent with progression toward neoplastic transformation in the Serous Carcinogenesis Sequence. These changes may be pre-malignant and could represent an important phase in early neoplasia. ALDH1 activation in pBSO samples and its extinction in STICs should be considered as a target for prevention.
authors.affiliation: Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France; EA ERTICa, Université d'Auvergne, Clermont-Ferrand, France; Department of Gynecology, CHU Lyon, Lyon, France. Electronic address: chenegautier@yahoo.fr.
authors.forename: Gautier
authors.initials: G
authors.lastname: Chene
authors.affiliation: Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France; EA ERTICa, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Cayre
authors.affiliation: Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France; EA ERTICa, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Ines
authors.initials: I
authors.lastname: Raoelfils
authors.affiliation: Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France; EA ERTICa, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lagarde
authors.affiliation: Department of Surgery, Centre Jean Perrin, Clermont-Ferrand, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Dauplat
authors.affiliation: Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France; EA ERTICa, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Frederique
authors.initials: F
authors.lastname: Penault-Llorca
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005184:Fallopian Tube Diseases / Q000378:metabolism / Q000473:pathology*; D005185:Fallopian Tube Neoplasms / Q000378:metabolism / Q000473:pathology; D005187:Fallopian Tubes / Q000002:abnormalities* / Q000378:metabolism / Q000601:surgery; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D010049:Ovarian Diseases / Q000378:metabolism / Q000473:pathology*; D010052:Ovariectomy; D010053:Ovary / Q000002:abnormalities* / Q000378:metabolism / Q000601:surgery; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism; D058994:Salpingectomy; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; C468783:H2AX protein, human; D006657:Histones; D007527:Isoenzymes; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: ALDH 1; Ovarian cancer; Ovarian dysplasia; Prophylactic salpingo-oophorectomy; STIC