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Intratumoral lymphocyte density in serous ovarian carcinoma is superior to ERCC1 expression for predicting response to platinum-based therapy

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Abstract

Intratumoral immune cells and ERCC1 expression are likely to play a role in the response of ovarian carcinoma to chemotherapy, but their impact on therapy outcome is still unclear. Therefore, 41 cases of optimally resected high grade serous ovarian carcinomas were examined retrospectively for stromal and intraepithelial lymphocyte populations and ERCC1 status in relation to response to platinum-based therapy. Based on RECIST criteria, 27 patients were classified as responsive and 14 as therapy resistant, respectively. Using immunohistochemistry for CD3, CD8, CD4, TIA1, MUM1 and FOX P3 on representative tumor sections, we quantitatively evaluated the intratumoral density of lymphocyte subpopulations. In addition, ERCC1 protein and mRNA expression were determined by immunohistochemistry using the Steffensen score and quantitative RT-PCR, respectively. Furthermore, ERCC1 SNP’s C8092A and codon 118 were analysed. Response to chemotherapy was significantly associated with higher numbers of stromal CD3+ (mean 21.33 lymphocytes/HPF versus 8.21 lymphocytes/HPF, p = 0.002) and CD8+ lymphocytes (mean 9.22 lymphocytes/HPF versus 4.57 lymphocytes/HPF, p = 0.013). Counts of intraepithelial CD3+ and CD8+ lymphocytes, stromal and intraepithelial FOXP3+ and TIA1+ cells, CD4+ lymphocytes, and MUM1+ plasma cells did not reach statistical significance. Neither ERCC1 protein expression (p = 0.232) nor SNPs codon 118 and C8092A of the ERCC1 gene (p = 0.269 and p = 0.543) showed an association with therapy response. The same was true for ERCC1 mRNA levels (p = 0.896), probably due to intratumoral lymphocyte contamination. In conclusion, the density of CD3+ and CD8+ T-cells in tumor stroma proved to be a significant predictor for response to platinum-based therapy, whereas examination of ERCC1 failed to identify therapy-responsive patients.

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Abbreviations

ERCC1:

Excision repair cross-complementing rodent repair deficiency complementation group 1

HPF:

High power field

IHC:

Immunohistochemistry

IL:

Intraepithelial lymphocytes

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PFS:

Progression-free survival

SL:

Stromal lymphocytes

SNP:

Single nucleotide polymorphism

SOC:

Serous ovarian cancer

TBP:

TATA box-binding protein

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Pathology, Krankenhaus Barmherzige Schwestern Linz, Seilerstätte 4, 4020, Linz, Austria

    Hans Bösmüller & Sophie Haitchi-Petnehazy

  2. Laboratory of Molecular Biology, Krankenhaus Barmherzige Schwestern Linz, Linz, Austria

    Gerald Webersinke & Renate Marschon

  3. Department of Gynecology, Krankenhaus Barmherzige Schwestern Linz, Linz, Austria

    Franz Roithmeier & Wolfgang Stummvoll

  4. Department of Gynecology, University of Tübingen, Tübingen, Germany

    Tanja Fehm

  5. Department of Pathology, University of Tübingen, Tübingen, Germany

    Hans Bösmüller, Margit Klier-Richter, Irina Bonzheim, Annette Staebler & Falko Fend

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  1. Hans Bösmüller
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Correspondence to Hans Bösmüller.

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Bösmüller, H., Haitchi-Petnehazy, S., Webersinke, G. et al. Intratumoral lymphocyte density in serous ovarian carcinoma is superior to ERCC1 expression for predicting response to platinum-based therapy. Virchows Arch 459, 183–191 (2011). https://doi.org/10.1007/s00428-011-1110-1

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