The relevance of HLAtype in ovarian cancer.

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The relevance of HLA-type in ovarian cancer.

• Lisa Villabona

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It all started with
High frequency of HLA A2 among advanced
metastatic ovarian and prostate cancer patients
recruited to vaccine studies
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De Petris, 2004 94
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Malignant melanoma mortality and HLA-A2
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The prevalent ovarian cancer cohort .
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24/32 Serous Adeno CA
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HLA-A2 in prevalent ovarian cancer cohort
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24/32 Serous Adeno CA
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segregation
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• HLA-A2 as risk or prognostic factor?

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Methods

• Historical group
• (HLA-A2 as prognostic factor)
• Karolinska Hospital (year 1995)
• HLA-A2 typing on paraffin-embedded tissue blocks

• DNA Extraction
• -Roche High Pure Paraffin Embedded Kit
• DNA Amplification (PCR)
• -Sequence specific primers for HLA-A2
• Detection
• -gel electrophoresis

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The selection of patients
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Survival by Kaplan-Meyer analysis
P0.009
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Selected by Clinical stage (III-IV), HLA and
Seropapillary histology
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What do we do now?

• Association/segregation to HLA haplotypes (risk).
• HLA expression at the tumour level (down
  regulation, loss, relation to KIR).
• Genetic linkage to oncogenes.
• HLA role in other malignancies (melanoma,
  prostate and Head and Neck tumours).

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Thank you!

• Our group
• The boss Giuseppe V. Masucci
• No 2 Kjell Bergfeldt
• Zaynab Gamzatova
• Emilia Andersson
• Henk van der Zanden

• Collaborators
• Dept of oncology/pathology, Stockholm
• Tina Dalianis and group
• Gunilla Högberg and co-workers.
• Lena Kanter
• Institute of Medical Immunology, MLU, Halle
• Barbara Seliger and group

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Any linkage between HLA and P21Waf1/Cip1 and p53?

• From the literarture
• Auer G, Einhorn N, Nilsson B, Silfversward C,
  Sjovall K. Biological malignancy grading in
  early-stage ovarian carcinoma. Acta Oncol 199635
  Suppl 893-8.
• Meinhold-Heerlein I, Bauerschlag D, Hilpert F,
  Dimitrov P, Sapinoso LM, Orlowska-Volk M, et al.
  Molecular and prognostic distinction between
  serous ovarian carcinomas of varying grade and
  malignant potential. Oncogene 200524(6)1053-65.
• Bali A, O'Brien PM, Edwards LS, Sutherland RL,
  Hacker NF, Henshall SM. Cyclin D1, p53, and
  p21Waf1/Cip1 expression is predictive of poor
  clinical outcome in serous epithelial ovarian
  cancer. Clin Cancer Res 200410(15)5168-77.