title: Evolution in endometrial cancer: evidence from an immunohistochemical study.
abstract: BACKGROUND
  It is poorly described how endometrial cancer biology changes during tumor evolution. We hypothesize that characterization of molecular targets in recurrent lesions is more relevant for targeting treatment.
  
  
  METHODS
  Paired biopsies from primary and recurrent endometrial cancer tumors (n = 85) were stained immunohistochemically for the following proteins: estrogen receptor (ER), progesterone receptor (PR), stathmin (correlating with phosphatidylinositol 3-kinase activity), HER-2/neu, WT1 (Wilms tumor gene 1), phospho-mammalian target of rapamycin (p-mTOR), and p53. Each tumor was scored, using a semiquantitative and subjective grading system. Discordance, a change in expression between primary and recurrent tumor, was defined as ≥ 2 step change; concordance was ≤ 1 step change. The frequency of change was correlated with established prognostic markers in endometrial cancer.
  
  
  RESULTS
  Fifty-six patients (67%) were diagnosed with endometrioid carcinoma, 23 (27%) with serous/clear cell carcinoma. A change in expression between primary and recurrent tumor was noted in 7% to 31% of patients for ER, PR, stathmin, HER-2/neu, WT1, p-mTOR, and p53. Concordant-positive cases for PR were significantly correlated with stage, tumor grade, and histological subtype. Expression of ER, p53, and p-mTOR in cytoplasm in the recurrent tumor correlated significantly with survival.
  
  
  CONCLUSIONS
  Endometrial cancer biology changes over time. The decision on targeted treatment should preferably be based on recurrent tumor characteristics.
authors: Leuven Cancer Institute (LKI), Gynecologic Oncology, UZ Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Ingrid
authors: I
authors: Vandenput
authors: Jone
authors: J
authors: Trovik
authors: Karin
authors: K
authors: Leunen
authors: Elisabeth
authors: E
authors: Wik
authors: Ingunn
authors: I
authors: Stefansson
authors: Lars
authors: L
authors: Akslen
authors: Philippe
authors: P
authors: Moerman
authors: Ignace
authors: I
authors: Vergote
authors: Helga
authors: H
authors: Salvesen
authors: Frédéric
authors: F
authors: Amant
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004717:Endometrium / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D040081:Protein Array Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D050777:Stathmin / Q000096:biosynthesis; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025721:WT1 Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D050777:Stathmin; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins; C546842:MTOR protein, human; C508053:ERBB2 protein, human