Human leucocyte antigen (HLA) A2 as a negative clinical prognostic factor in patients with advanced ovarian cancer.
OBJECTIVE
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.
Department of Oncology-Pathology, Karolinska Institute, Radiumhemmet, P301057 Karolinska University Hospital, 17176 Stockholm, Sweden.
Zaynab
Z
Gamzatova
Lisa
L
Villabona
Liselotte
L
Dahlgren
Tina
T
Dalianis
Bo
B
Nillson
Kjell
K
Bergfeldt
Giuseppe V
GV
Masucci
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D015789:HLA-A2 Antigen / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate
D014408:Biomarkers, Tumor; D015789:HLA-A2 Antigen