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Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer

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Abstract

The role of CTLA-4 in negative regulation of T-cell mediated immune response is particularly well established. Much less is known about its expression and function in tumour cells, and to our knowledge, no data are available on its possible impact on prognosis of NSCLC patients. We investigated CTLA-4 expression and prognostic role in 81 patients with radically resected stage I–III NSCLC. The analysis was performed by tissue microarray immunohistochemistry, and the median H-score of 20 was used as a threshold to define CTLA-4 overexpressing tumours. Correlation with standard prognostic factors was performed by using absolute and relative fold change indexes. Hazard ratios (HR) and corresponding 95% confidence limits (95% CL) were computed through the Cox model. A higher frequency of CTLA-4 overexpression (>20) was found in non-squamous than in squamous NSCLC (52.8 vs. 35.7%) and in Ki67 ≤ 15 expressing tumours, as compared to those with Ki67 > 15 (51.5 vs. 38.7%). A reduced death rate was found in CTLA-4 overexpressing tumours (HR = 0.60, 95% CL = 0.28/1.23), and a further decrease was observed when considering tumours with CTLA-4 > 20 and Ki67 ≤ 15, in comparison with tumours with CTLA-4 ≤ 20 and Ki67 > 15 (HR = 0.41; 95% CL = 0.15/1.13). Our observational and exploratory study provides a first and promising indication for an independent prognostic effect of CTLA-4 overexpression in radically resected NSCLC. We presume that this effect relies on modulation of the interaction of microscopic disease with CTLA-4-ligands expressing cells leading to NSCLC cell death.

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Acknowledgments

This work was supported in parts by grants from Alleanza Contro il Cancro, Rome (Italy), and from Ricerca Sanitaria Regione Liguria (Italy) 2009. The authors would like to thank Alessandro Poggi for fruitful discussions and helpful comments.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, IRCCS A.O.U. San Martino-IST, Genoa, Italy

    Sandra Salvi, Simona Boccardo, Edoardo Margallo, Marco Mora & Mauro Truini

  2. Unit of Epidemiology, Biostatistics and Clinical Trials, IRCCS A.O.U. San Martino-IST, Genoa, Italy

    Vincenzo Fontana & Domenico Franco Merlo

  3. Tumour Genetics and Epigenetics, IRCCS A.O.U. San Martino-IST, Largo Rosanna Benzi, 10, 16132, Genoa, Italy

    Stefania Laurent, Anna Morabito & Maria Pia Pistillo

  4. Lung Cancer Unit, IRCCS A.O.U. San Martino-IST, Genoa, Italy

    Erika Rijavec, Maria Giovanna Dal Bello & Francesco Grossi

  5. Unit of Thoracic Surgery, IRCCS A.O.U. San Martino-IST, Genoa, Italy

    Giovanni Battista Ratto

Authors
  1. Sandra Salvi
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  2. Vincenzo Fontana
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  3. Simona Boccardo
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  4. Domenico Franco Merlo
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  6. Stefania Laurent
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  9. Maria Giovanna Dal Bello
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  10. Marco Mora
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  12. Francesco Grossi
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  13. Mauro Truini
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  14. Maria Pia Pistillo
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Correspondence to Maria Pia Pistillo.

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Salvi, S., Fontana, V., Boccardo, S. et al. Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer. Cancer Immunol Immunother 61, 1463–1472 (2012). https://doi.org/10.1007/s00262-012-1211-y

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  • DOI: https://doi.org/10.1007/s00262-012-1211-y

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