Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma

Abir Salwa Ali; Malin Grönberg; Birgitte Federspiel; Jean Yves Scoazec; Geir Olav Hjortland; Henning Grønbæk; Morten Ladekarl; Seppo W. Langer; Staffan Welin; Lene Weber Vestermark; Johanna Arola; Pia Österlund; Ulrich Knigge; Halfdan Sorbye; Lars Grimelius; Eva Tiensuu Janson

doi:10.1371/journal.pone.0187667

Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma

Abir Salwa Ali, Malin Grönberg, Birgitte Federspiel, Jean Yves Scoazec, Geir Olav Hjortland, Henning Grønbæk, Morten Ladekarl, Seppo W. Langer, Staffan Welin, Lene Weber Vestermark, Johanna Arola, Pia Österlund, Ulrich Knigge, Halfdan Sorbye, Lars Grimelius, Eva Tiensuu Janson^*

^*Corresponding author for this work

Department of Clinical Medicine

13 Citations (Scopus)

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Abstract

Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreactive p53 protein in GEP-NEC. Materials and methods Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS). Results All tumor tissues were immunoreactive for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS in patients with colorectal tumors (HR = 2.1, p = 0.03) in a univariate analysis as well as to poorer PFS (HR = 2.6, p = 0.03) and OS (HR = 3.4, p = 0.02) in patients with colorectal tumors with distant metastases, a correlation which remained significant in the multivariate analyses. Conclusion In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.

Original language	English
Article number	e0187667
Journal	PLOS ONE
Volume	12
Issue number	11
Number of pages	15
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0187667
Publication status	Published - Nov 2017

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Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinomaFinal published version, 20.6 MBLicence: CC BY

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Ali, A. S., Grönberg, M., Federspiel, B., Scoazec, J. Y., Hjortland, G. O., Grønbæk, H., Ladekarl, M., Langer, S. W., Welin, S., Vestermark, L. W., Arola, J., Österlund, P., Knigge, U., Sorbye, H., Grimelius, L., & Janson, E. T. (2017). Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma. PLOS ONE, 12(11), [e0187667]. https://doi.org/10.1371/journal.pone.0187667

Ali, AS, Grönberg, M, Federspiel, B, Scoazec, JY, Hjortland, GO, Grønbæk, H, Ladekarl, M, Langer, SW, Welin, S, Vestermark, LW, Arola, J, Österlund, P, Knigge, U, Sorbye, H, Grimelius, L & Janson, ET 2017, 'Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma', PLOS ONE, vol. 12, no. 11, e0187667. https://doi.org/10.1371/journal.pone.0187667

@article{72a715507a5346a09d1ca9735ee4d336,

title = "Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma",

abstract = "Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreactive p53 protein in GEP-NEC. Materials and methods Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS). Results All tumor tissues were immunoreactive for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS in patients with colorectal tumors (HR = 2.1, p = 0.03) in a univariate analysis as well as to poorer PFS (HR = 2.6, p = 0.03) and OS (HR = 3.4, p = 0.02) in patients with colorectal tumors with distant metastases, a correlation which remained significant in the multivariate analyses. Conclusion In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.",

author = "Ali, {Abir Salwa} and Malin Gr{\"o}nberg and Birgitte Federspiel and Scoazec, {Jean Yves} and Hjortland, {Geir Olav} and Henning Gr{\o}nb{\ae}k and Morten Ladekarl and Langer, {Seppo W.} and Staffan Welin and Vestermark, {Lene Weber} and Johanna Arola and Pia {\"O}sterlund and Ulrich Knigge and Halfdan Sorbye and Lars Grimelius and Janson, {Eva Tiensuu}",

year = "2017",

month = nov,

doi = "10.1371/journal.pone.0187667",

language = "English",

volume = "12",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "11",

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TY - JOUR

T1 - Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma

AU - Ali, Abir Salwa

AU - Grönberg, Malin

AU - Federspiel, Birgitte

AU - Scoazec, Jean Yves

AU - Hjortland, Geir Olav

AU - Grønbæk, Henning

AU - Ladekarl, Morten

AU - Langer, Seppo W.

AU - Welin, Staffan

AU - Vestermark, Lene Weber

AU - Arola, Johanna

AU - Österlund, Pia

AU - Knigge, Ulrich

AU - Sorbye, Halfdan

AU - Grimelius, Lars

AU - Janson, Eva Tiensuu

PY - 2017/11

Y1 - 2017/11

N2 - Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreactive p53 protein in GEP-NEC. Materials and methods Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS). Results All tumor tissues were immunoreactive for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS in patients with colorectal tumors (HR = 2.1, p = 0.03) in a univariate analysis as well as to poorer PFS (HR = 2.6, p = 0.03) and OS (HR = 3.4, p = 0.02) in patients with colorectal tumors with distant metastases, a correlation which remained significant in the multivariate analyses. Conclusion In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.

AB - Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreactive p53 protein in GEP-NEC. Materials and methods Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS). Results All tumor tissues were immunoreactive for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS in patients with colorectal tumors (HR = 2.1, p = 0.03) in a univariate analysis as well as to poorer PFS (HR = 2.6, p = 0.03) and OS (HR = 3.4, p = 0.02) in patients with colorectal tumors with distant metastases, a correlation which remained significant in the multivariate analyses. Conclusion In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.

U2 - 10.1371/journal.pone.0187667

DO - 10.1371/journal.pone.0187667

M3 - Journal article

C2 - 29112960

AN - SCOPUS:85033222567

SN - 1932-6203

VL - 12

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 11

M1 - e0187667

ER -

Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma

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