title: HOXB8 expression in ovarian serous carcinoma effusions is associated with shorter survival.
abstract: OBJECTIVE
  HOX proteins are key transcription factors in embryogenesis. HOXB5 and HOXB8 were previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared to breast carcinoma using gene expression arrays. The present study investigated the clinical role of HOXB5 and HOXB8 in advanced-stage (FIGO III-IV) ovarian serous carcinoma.
  
  
  METHODS
  HOXB5 and HOXB8 protein expression was analyzed in 286 effusions and 76 patient-matched solid lesions (27 primary carcinomas, 49 metastases) using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including survival.
  
  
  RESULTS
  Cytoplasmic HOXB5 protein was detected in 268/286 (94%) effusions. HOXB8 was expressed at both the cytoplasm (252/286; 88%) and nucleus (131/286; 46%) of carcinoma cells. Cytoplasmic HOXB5, cytoplasmic HOXB8 and nuclear HOXB8 were found in 56/76 (74%), 76/76 (100%) and 30/76 (39%) solid lesions, respectively, with significantly higher HOXB5 expression in effusions (p=0.002) and higher cytoplasmic HOXB8 in solid lesions (p<0.001). HOXB5 expression was higher in post-chemotherapy disease recurrence effusions compared to pre-chemotherapy effusions tapped at diagnosis (p=0.04). In univariate survival analysis of the effusion cohort, higher expression of cytoplasmic HOXB8 was associated with significantly shorter progression-free survival (p=0.033), whereas higher nuclear HOXB8 expression was associated with significantly shorter overall survival in analysis limited to patients with post-chemotherapy effusions (p=0.036). Neither finding was independent prognostic factor in Cox multivariate analysis.
  
  
  CONCLUSIONS
  HOXB5 and HOXB8 are frequently expressed in ovarian serous carcinoma, with anatomic site-related differences for cytoplasmic staining. HOXB5 may be affected by chemotherapy in effusions. HOXB8 expression is associated with shorter survival in metastatic serous carcinoma.
authors: Division of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway.
authors: Helene Tuft
authors: HT
authors: Stavnes
authors: Arild
authors: A
authors: Holth
authors: Trinh
authors: T
authors: Don
authors: Janne
authors: J
authors: Kærn
authors: Olga
authors: O
authors: Vaksman
authors: Reuven
authors: R
authors: Reich
authors: Claes G
authors: CG
authors: Trope'
authors: Ben
authors: B
authors: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D017024:Chemotherapy, Adjuvant; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C489126:HOXB5 protein, human; C490669:HOXB8 protein, human; D018398:Homeodomain Proteins