Human leucocyte antigen (HLA) A2 as a negative clinical prognostic factor in patients with advanced ovarian cancer

Gynecol Oncol. 2006 Oct;103(1):145-50. doi: 10.1016/j.ygyno.2006.02.004. Epub 2006 Mar 20.

Abstract

Objectives: Major histocompatibility complex antigens are mandatory for the immune response, and a genetic imbalance may be linked to tumor escape. We have previously characterized a cluster of ovarian cancer patients with high incidence of HLA-A2. To find a prognostic relevance, the presence of HLA-A2 was correlated to defined clinical parameters.

Methods: A population-based set of 97 patients with confirmed epithelial ovarian cancer were recorded in a database by age, histology, stage, surgery and treatment. At the time the study was initiated, the majority of the patients were not alive and HLA-A2 expression was therefore determined by PCR/sequence-specific oligonucleotide hybridization using DNA extracted from paraffin-imbedded tissue specimens.

Results: 88 patients with a median age of 65 years (36-87) could be evaluated. 44% were serous adenocarcinomas, 28% endometrioid, 6% mucinous, 13% clear cell carcinomas, 7% undifferentiated and 2% other epithelial tumors. Stages I-II comprised 33% and stages III-IV 67%. In stages III-IV and serous histology, 73% were HLA-A2 positive. Cox analysis, in this group, showed high univariate (HR7.16; CI 2.04-25.03; P = 0.002) and multivariate (HR 6.8; CI 2.10-22.4; P = 0.001) Hazard Ratios. None of the HLA-A2 positive patients survived 5 years, compared to more than 50% of the HLA-A2 negative patients.

Conclusions: HLA-A2 is a negative factor for survival in women with serous adenocarcinomas of the ovary in stages III-IV. This finding has implications for clinical patient management. Association with known oncogenes needs further analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Endometrioid / drug therapy
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / immunology
  • Carcinoma, Endometrioid / pathology
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / immunology
  • Cystadenocarcinoma, Serous / pathology
  • Female
  • HLA-A2 Antigen / biosynthesis*
  • HLA-A2 Antigen / genetics
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • Paraffin Embedding
  • Polymerase Chain Reaction
  • Prognosis
  • Proportional Hazards Models
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • HLA-A2 Antigen