title: Tissue content of hydroxyestrogens in relation to survival of breast cancer patients.
abstract: OBJECTIVE
  The main goal of our study was to assess estrogen contents of breast tumor tissues, having different estrogen receptor status, in relation to long-term follow-up of patients.
  
  
  METHODS
  Twenty-one breast cancer cases, all collected from January 1986 to January 1988 at the M. Ascoli Cancer Hospital Centre in Palermo, were included in the study and compared with 6 healthy women as a control group. Average follow-up time of patients was 144 +/- 10 months. The estrogen receptor status of tissues was determined by both ligand binding and immunohistochemical assays. A high performance liquid chromatography-based approach, jointly with gas chromatography/mass spectrometry, was used to identify and measure main estrogens, various hydroxyestrogens, and their methoxy derivatives in both normal and tumor tissues.
  
  
  RESULTS
  Although variable concentrations of hydroxylated estrogens were detected, they consistently accounted for >80% of all of the estrogens. Significantly greater amounts of both 2- and 4-hydroxyestradiol, along with a marked increase of 16 alpha-hydroxyestrone (OHE(1)), were observed in cancer with respect to normal breast tissues. A significant positive association was observed with elevated 16 alpha OHE(1) (P = 0.015) in patients alive, leading to significantly lower (P = 0.043) 2OHE(1):16 alpha OHE(1) ratio values. Conversely, ratio values of 4:2 hydroxy+methoxy estrogens was significantly lower (P = 0.006) in deceased patients. Using cutoff values of 1.2 for 4:2 hydroxy+methoxy ratio and 150 fmol/mg tissue for 16 alpha OHE(1) we achieved a clear-cut separation of patients, with over-cutoff patients having 147 months and under cutoff patients showing only 47 months median survival time (P = 0.00008).
  
  
  CONCLUSIONS
  Our data imply that individual hydroxyestrogens may have a distinct role in the onset and the clinical progression of breast cancer, with greater 16 alpha OHE(1) levels being in turn associated to cancer with respect to normal tissues and to a prolonged survival of breast cancer patients.
authors.affiliation: Department of Experimental Oncology and Clinical Application, University Medical School, Palermo 90127, Italy. lucashbl@unipa.it
authors.forename: Luigi A M
authors.initials: LA
authors.lastname: Castagnetta
authors.forename: Orazia M
authors.initials: OM
authors.lastname: Granata
authors.forename: Adele
authors.initials: A
authors.lastname: Traina
authors.forename: Barbara
authors.initials: B
authors.lastname: Ravazzolo
authors.forename: Maria
authors.initials: M
authors.lastname: Amoroso
authors.forename: Monica
authors.initials: M
authors.lastname: Miele
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bellavia
authors.forename: Biagio
authors.initials: B
authors.lastname: Agostara
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carruba
mesh_terms: D000328:Adult; D000368:Aged; D001665:Binding Sites; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality*; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000031:analogs & derivatives* / Q000032:analysis*; D004967:Estrogens / Q000032:analysis; D002393:Estrogens, Catechol; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006894:Hydroxyestrones / Q000032:analysis*; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate
chemical_list: D004967:Estrogens; D002393:Estrogens, Catechol; D006894:Hydroxyestrones; D011960:Receptors, Estrogen; C026702:16-hydroxyestrone; D004958:Estradiol; C001390:2-hydroxyestradiol; C014036:4-hydroxyestradiol