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Published in: Virchows Archiv 4/2018

01-10-2018 | Original Article

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

Authors: Catarina Ferreira, João Lobo, Luís Antunes, Paula Lopes, Carmen Jerónimo, Rui Henrique

Published in: Virchows Archiv | Issue 4/2018

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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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Literature
3.
go back to reference Etzioni R, Penson DF, Legler JM, di Tommaso D, Boer R, Gann PH, Feuer EJ (2002) Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends. J Natl Cancer Inst 94(13):981–990CrossRef Etzioni R, Penson DF, Legler JM, di Tommaso D, Boer R, Gann PH, Feuer EJ (2002) Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends. J Natl Cancer Inst 94(13):981–990CrossRef
4.
go back to reference Potosky AL, Miller BA, Albertsen PC, Kramer BS (1995) The role of increasing detection in the rising incidence of prostate cancer. JAMA 273(7):548–552CrossRef Potosky AL, Miller BA, Albertsen PC, Kramer BS (1995) The role of increasing detection in the rising incidence of prostate cancer. JAMA 273(7):548–552CrossRef
6.
8.
go back to reference Miller GJ, Torkko KC (2001) Natural history of prostate cancer--epidemiologic considerations. Epidemiol Rev 23(1):14–18CrossRef Miller GJ, Torkko KC (2001) Natural history of prostate cancer--epidemiologic considerations. Epidemiol Rev 23(1):14–18CrossRef
9.
go back to reference Adolfsson J, Rönström L, Carstensen J, Löwhagen T, Hedlund PO (1990) The natural course of low grade, non-metastatic prostatic carcinoma. Br J Urol 65(6):611–614CrossRef Adolfsson J, Rönström L, Carstensen J, Löwhagen T, Hedlund PO (1990) The natural course of low grade, non-metastatic prostatic carcinoma. Br J Urol 65(6):611–614CrossRef
10.
go back to reference Bostwick DG, Graham SD, Napalkov P, Abrahamsson PA, di Sant'agnese PA, Algaba F, Hoisaeter PA, Lee F, Littrup P, Mostofi FK (1993) Staging of early prostate cancer: a proposed tumor volume-based prognostic index. Urology 41(5):403–411CrossRef Bostwick DG, Graham SD, Napalkov P, Abrahamsson PA, di Sant'agnese PA, Algaba F, Hoisaeter PA, Lee F, Littrup P, Mostofi FK (1993) Staging of early prostate cancer: a proposed tumor volume-based prognostic index. Urology 41(5):403–411CrossRef
12.
go back to reference Bauer JJ, Connelly RR, Seterhenn IA, Deausen J, Srivastava S, McLeod DG, Moul JW (1998) Biostatistical modeling using traditional preoperative and pathological prognostic variables in the selection of men at high risk for disease recurrence after radical prostatectomy for prostate cancer. J Urol 159(3):929–933CrossRef Bauer JJ, Connelly RR, Seterhenn IA, Deausen J, Srivastava S, McLeod DG, Moul JW (1998) Biostatistical modeling using traditional preoperative and pathological prognostic variables in the selection of men at high risk for disease recurrence after radical prostatectomy for prostate cancer. J Urol 159(3):929–933CrossRef
17.
go back to reference Deng QK, Lei YG, Lin YL, Ma JG, Li WP (2016) Prognostic value of protocadherin10 (PCDH10) methylation in serum of prostate cancer patients. Med Sci Monit 22:516–521CrossRef Deng QK, Lei YG, Lin YL, Ma JG, Li WP (2016) Prognostic value of protocadherin10 (PCDH10) methylation in serum of prostate cancer patients. Med Sci Monit 22:516–521CrossRef
18.
go back to reference Soler AP, Harner GD, Knudsen KA, McBrearty FX, Grujic E, Salazar H, Han AC, Keshgegian AA (1997) Expression of P-cadherin identifies prostate-specific-antigen-negative cells in epithelial tissues of male sexual accessory organs and in prostatic carcinomas. Implications for prostate cancer biology. Am J Pathol 151(2):471–478PubMedPubMedCentral Soler AP, Harner GD, Knudsen KA, McBrearty FX, Grujic E, Salazar H, Han AC, Keshgegian AA (1997) Expression of P-cadherin identifies prostate-specific-antigen-negative cells in epithelial tissues of male sexual accessory organs and in prostatic carcinomas. Implications for prostate cancer biology. Am J Pathol 151(2):471–478PubMedPubMedCentral
19.
go back to reference Berx G, Van Roy F (2001) The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res 3(5):289–293CrossRef Berx G, Van Roy F (2001) The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res 3(5):289–293CrossRef
21.
go back to reference Van Aken E, De Wever O, Correia da Rocha AS, Mareel M (2001) Defective E-cadherin/catenin complexes in human cancer. Virchows Arch 439(6):725–751CrossRef Van Aken E, De Wever O, Correia da Rocha AS, Mareel M (2001) Defective E-cadherin/catenin complexes in human cancer. Virchows Arch 439(6):725–751CrossRef
24.
go back to reference Bae KM, Parker NN, Dai Y, Vieweg J, Siemann DW (2011) E-cadherin plasticity in prostate cancer stem cell invasion. Am J Cancer Res 1(1):71–84PubMed Bae KM, Parker NN, Dai Y, Vieweg J, Siemann DW (2011) E-cadherin plasticity in prostate cancer stem cell invasion. Am J Cancer Res 1(1):71–84PubMed
26.
33.
go back to reference Tang LH, Berlin J, Branton P, Burgart LJ, Carter DK, Compton CC, Fitzgibbons P, Frankel WL, Jessup J, Kakar S, Minsky B, Nakhleh R, Washington K (2013) Protocol for the examination of specimens from patients with carcinoma of the stomach. Gastrointestinal - Stomach, vol Stomach 3.2.0.1. College of American Pathologists (CAP). Based on AJCC/UICC TNM, 7th edition. http://www.cap.org/cancerprotocols. Accessed 1 Oct 2017 Tang LH, Berlin J, Branton P, Burgart LJ, Carter DK, Compton CC, Fitzgibbons P, Frankel WL, Jessup J, Kakar S, Minsky B, Nakhleh R, Washington K (2013) Protocol for the examination of specimens from patients with carcinoma of the stomach. Gastrointestinal - Stomach, vol Stomach 3.2.0.1. College of American Pathologists (CAP). Based on AJCC/UICC TNM, 7th edition. http://​www.​cap.​org/​cancerprotocols. Accessed 1 Oct 2017
35.
go back to reference Howlader N, Noone A, Krapcho M, Miller D, Bishop K, Kosary C, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis D, Chen H, Feuer E, Cronin K (2017) SEER Cancer Statistics Review, 1975–2014, National Cancer Institute. https://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data submission, posted to the SEER web site, April 2017. Bethesda, MD Howlader N, Noone A, Krapcho M, Miller D, Bishop K, Kosary C, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis D, Chen H, Feuer E, Cronin K (2017) SEER Cancer Statistics Review, 1975–2014, National Cancer Institute. https://​seer.​cancer.​gov/​csr/​1975_​2014/​, based on November 2016 SEER data submission, posted to the SEER web site, April 2017. Bethesda, MD
40.
go back to reference Richmond PJ, Karayiannakis AJ, Nagafuchi A, Kaisary AV, Pignatelli M (1997) Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation with patient survival. Cancer Res 57(15):3189–3193PubMed Richmond PJ, Karayiannakis AJ, Nagafuchi A, Kaisary AV, Pignatelli M (1997) Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation with patient survival. Cancer Res 57(15):3189–3193PubMed
41.
go back to reference Loric S, Paradis V, Gala JL, Berteau P, Bedossa P, Benoit G, Eschwège P (2001) Abnormal E-cadherin expression and prostate cell blood dissemination as markers of biological recurrence in cancer. Eur J Cancer 37(12):1475–1481CrossRef Loric S, Paradis V, Gala JL, Berteau P, Bedossa P, Benoit G, Eschwège P (2001) Abnormal E-cadherin expression and prostate cell blood dissemination as markers of biological recurrence in cancer. Eur J Cancer 37(12):1475–1481CrossRef
42.
go back to reference van Oort IM, Tomita K, van Bokhoven A, Bussemakers MJ, Kiemeney LA, Karthaus HF, Witjes JA, Schalken JA (2007) The prognostic value of E-cadherin and the cadherin-associated molecules alpha-, beta-, gamma-catenin and p120ctn in prostate cancer specific survival: a long-term follow-up study. Prostate 67(13):1432–1438. https://doi.org/10.1002/pros.20626 CrossRefPubMed van Oort IM, Tomita K, van Bokhoven A, Bussemakers MJ, Kiemeney LA, Karthaus HF, Witjes JA, Schalken JA (2007) The prognostic value of E-cadherin and the cadherin-associated molecules alpha-, beta-, gamma-catenin and p120ctn in prostate cancer specific survival: a long-term follow-up study. Prostate 67(13):1432–1438. https://​doi.​org/​10.​1002/​pros.​20626 CrossRefPubMed
46.
go back to reference Paredes J, Figueiredo J, Albergaria A, Oliveira P, Carvalho J, Ribeiro AS, Caldeira J, Costa AM, Simões-Correia J, Oliveira MJ, Pinheiro H, Pinho SS, Mateus R, Reis CA, Leite M, Fernandes MS, Schmitt F, Carneiro F, Figueiredo C, Oliveira C, Seruca R (2012) Epithelial E- and P-cadherins: role and clinical significance in cancer. Biochim Biophys Acta 1826(2):297–311. https://doi.org/10.1016/j.bbcan.2012.05.002 CrossRefPubMed Paredes J, Figueiredo J, Albergaria A, Oliveira P, Carvalho J, Ribeiro AS, Caldeira J, Costa AM, Simões-Correia J, Oliveira MJ, Pinheiro H, Pinho SS, Mateus R, Reis CA, Leite M, Fernandes MS, Schmitt F, Carneiro F, Figueiredo C, Oliveira C, Seruca R (2012) Epithelial E- and P-cadherins: role and clinical significance in cancer. Biochim Biophys Acta 1826(2):297–311. https://​doi.​org/​10.​1016/​j.​bbcan.​2012.​05.​002 CrossRefPubMed
47.
go back to reference Bussemakers MJ, van Moorselaar RJ, Giroldi LA, Ichikawa T, Isaacs JT, Takeichi M, Debruyne FM, Schalken JA (1992) Decreased expression of E-cadherin in the progression of rat prostatic cancer. Cancer Res 52(10):2916–2922PubMed Bussemakers MJ, van Moorselaar RJ, Giroldi LA, Ichikawa T, Isaacs JT, Takeichi M, Debruyne FM, Schalken JA (1992) Decreased expression of E-cadherin in the progression of rat prostatic cancer. Cancer Res 52(10):2916–2922PubMed
48.
go back to reference Umbas R, Isaacs WB, Bringuier PP, Schaafsma HE, Karthaus HF, Oosterhof GO, Debruyne FM, Schalken JA (1994) Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res 54(14):3929–3933PubMed Umbas R, Isaacs WB, Bringuier PP, Schaafsma HE, Karthaus HF, Oosterhof GO, Debruyne FM, Schalken JA (1994) Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res 54(14):3929–3933PubMed
49.
go back to reference Arenas MI, Romo E, Royuela M, Fraile B, Paniagua R (2000) E-, N- and P-cadherin, and alpha-, beta- and gamma-catenin protein expression in normal, hyperplastic and carcinomatous human prostate. Histochem J 32(11):659–667CrossRef Arenas MI, Romo E, Royuela M, Fraile B, Paniagua R (2000) E-, N- and P-cadherin, and alpha-, beta- and gamma-catenin protein expression in normal, hyperplastic and carcinomatous human prostate. Histochem J 32(11):659–667CrossRef
51.
go back to reference Jarrard DF, Paul R, van Bokhoven A, Nguyen SH, Bova GS, Wheelock MJ, Johnson KR, Schalken J, Bussemakers M, Isaacs WB (1997) P-cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer. Clin Cancer Res 3(11):2121–2128PubMed Jarrard DF, Paul R, van Bokhoven A, Nguyen SH, Bova GS, Wheelock MJ, Johnson KR, Schalken J, Bussemakers M, Isaacs WB (1997) P-cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer. Clin Cancer Res 3(11):2121–2128PubMed
53.
go back to reference Imai K, Hirata S, Irie A, Senju S, Ikuta Y, Yokomine K, Harao M, Inoue M, Tsunoda T, Nakatsuru S, Nakagawa H, Nakamura Y, Baba H, Nishimura Y (2008) Identification of a novel tumor-associated antigen, cadherin 3/P-cadherin, as a possible target for immunotherapy of pancreatic, gastric, and colorectal cancers. Clin Cancer Res 14(20):6487–6495. https://doi.org/10.1158/1078-0432.CCR-08-1086 CrossRefPubMed Imai K, Hirata S, Irie A, Senju S, Ikuta Y, Yokomine K, Harao M, Inoue M, Tsunoda T, Nakatsuru S, Nakagawa H, Nakamura Y, Baba H, Nishimura Y (2008) Identification of a novel tumor-associated antigen, cadherin 3/P-cadherin, as a possible target for immunotherapy of pancreatic, gastric, and colorectal cancers. Clin Cancer Res 14(20):6487–6495. https://​doi.​org/​10.​1158/​1078-0432.​CCR-08-1086 CrossRefPubMed
Metadata
Title
Differential expression of E-cadherin and P-cadherin in pT3 prostate cancer: correlation with clinical and pathological features
Authors
Catarina Ferreira
João Lobo
Luís Antunes
Paula Lopes
Carmen Jerónimo
Rui Henrique
Publication date
01-10-2018
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 4/2018
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-018-2406-1

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