title: COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?
abstract: OBJECTIVE
  Uterine carcinosarcomas are uncommon, highly aggressive neoplasms that frequently recur after surgical treatment and adjuvant chemo-radiotherapy. Patients with recurrent disease respond poorly to salvage chemotherapy and irradiation. New therapeutic options are required for patients with metastatic disease. Clinical evidences showing the effect of a tyrosine kinase inhibitor, STI571, in c-KIT-positive gastrointestinal tumors, the role of COX-inhibitors chemotherapy-associated in colorectal cancer patients and the successful therapeutic possibility of anti-HER2 therapy in metastatic breast carcinoma, have encouraged us to study the expression of c-KIT, COX-2 and HER-2/neu in uterine carcinosarcomas.
  
  
  METHODS
  We analyzed the expression of COX-2, c-KIT and HER-2/neu in 24 uterine carcinosarcomas and their correlation with clinical outcome. Disease-free interval and actuarial survival rates were the end points of the study.
  
  
  RESULTS
  High staining intensity for COX-2 was observed in 8 cases (33.3%). C-KIT was expressed in 4 cases (16.7%) and HER-2/neu in 7 cases (29.2%). Patients with COX-2-positive tumors had a significantly poorer disease-free interval and survival (P = 0.01 and P = 0.05, respectively). All patients with c-KIT-positive tumors had early stage disease. In spite of this, their survival was not significantly better than that of c-KIT-negative cases. HER-2/neu expression did not show any correlation with clinical outcome.
  
  
  CONCLUSIONS
  c-KIT, COX-2, and HER-2/neu were expressed in different proportions of uterine carcinosarcomas. COX-2 expression was a strong indicator of unfavorable prognosis. These results warrant further study to evaluate the possible role of a new molecularly targeted cancer therapy with COX-2 inhibitors in patients with uterine carcinosarcomas. The role of c-KIT expression and consequently the hypothetical use of STI571 should be tested in a larger series.
authors.affiliation: Department of Human Pathology and Oncology, University of Florence, School of Medicine, 85, 50134 Florence, Italy. mariarosaria.raspollini@unifi.it
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Raspollini
authors.forename: Tommaso
authors.initials: T
authors.lastname: Susini
authors.forename: Gianni
authors.initials: G
authors.lastname: Amunni
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.forename: Antonio
authors.initials: A
authors.lastname: Taddei
authors.forename: Mauro
authors.initials: M
authors.lastname: Marchionni
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Scarselli
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Taddei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002296:Carcinosarcoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D051546:Cyclooxygenase 2; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D008875:Middle Aged; D009336:Necrosis; D009367:Neoplasm Staging; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*
chemical_list: D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D007527:Isoenzymes; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases; C496540:PTGS2 protein, human