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Differential expression of E-cadherin and P-cadherin in pT3 prostate cancer: correlation with clinical and pathological features

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Abstract

Cadherins seem to play and important role in prostate cancer (PCa) progression. E-cadherin loss of expression has been associated with poor prognosis; P-cadherin’s role is still elusive. Although pT3 PCa is often considered “high-risk cancer,” it does not exhibit an uniformly poor prognosis. Herein, we assessed the prognostic value and survival impact of E-cadherin and P-cadherin immunoexpression in pT3 PCa. Radical prostatectomy (RP) specimens from 102 pT3 PCa patients treated between 1991 and 2014 in a single institution were designated for E-cadherin and P-cadherin immunoexpression analysis. A representative block from each specimen was selected for tissue micro-array (TMA) construction, using 3 cores per case. E-cadherin immunoexpression was assessed via a digital image analysis system. For P-cadherin, scoring criteria for HER2 in gastric cancer were used. Clinical records of all patients were reviewed for baseline clinical/pathologic characteristics and follow-up data. E-cadherin-low PCa patients displayed worse disease-specific survival (DSS), although not reaching statistical significance (HR 2.65, 95%CI 0.81–7.88). However, considering the pT3b group only, those with low E-cadherin immunoexpression displayed significantly worse overall-survival (OS) and DSS (HR 3.69, 95%CI 1.18–11.50; HR 5.90, 95%CI 1.40–24.81). No significant differences in survival were found for P-cadherin differential immunoexpression. Furthermore, an association between E-cadherin and P-cadherin immunoexpression (p = 0.019) was found, as among E-cadherin-low PCa, 96.6% were P-cadherin negative. We demonstrated that low E-cadherin immunoexpression discriminates among pT3b PCa patients those with poorer survival and which might benefit from specific therapy. The role of P-cadherin in PCa seems context-dependent deserving further investigation.

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Funding

This study was supported by project CI-IPOP-17-2015 (Epigenetic signature of prostate cancer stem cells) funded by the Research Centre of Portuguese Oncology Institute of Porto. JL is supported by an FCT—Fundação para a Ciência e Tecnologia—fellowship (grant number SFRH/BD/132751/2017).

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Authors and Affiliations

  1. Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

    Catarina Ferreira, João Lobo, Paula Lopes & Rui Henrique

  2. Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

    João Lobo, Paula Lopes, Carmen Jerónimo & Rui Henrique

  3. Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513, Porto, Portugal

    João Lobo, Carmen Jerónimo & Rui Henrique

  4. Department of Epidemiology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

    Luís Antunes

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  1. Catarina Ferreira
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Contributions

CF, JL, and RH designed the study; CF, JL, and PL performed technical procedures and acquired pathological and clinical data; CF, JL, CJ and RH analyzed and interpreted data; CF, JL, and LA performed statistical analysis; CF drafted the manuscript; all authors reviewed and approved the final version of the manuscript. All individuals listed as co-authors of the manuscript have significantly contributed to this study.

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Correspondence to Rui Henrique.

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This study was approved by the institutional ethics committee of Portuguese Oncology Institute Porto (Comissão de Ética para a Saúde do IPO Porto—CES 235/2017).

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The authors declare that they have no conflict of interest.

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Ferreira, C., Lobo, J., Antunes, L. et al. Differential expression of E-cadherin and P-cadherin in pT3 prostate cancer: correlation with clinical and pathological features. Virchows Arch 473, 443–452 (2018). https://doi.org/10.1007/s00428-018-2406-1

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