Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{76eeceaa984e46a3bc0e7eab93013292,
title = "P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms",
abstract = "BACKGROUND: High grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) with a Ki67 proliferation index > 20{\%}, include well-differentiated tumours grade 3 (NET G3) and poorly differentiated (PD) neuroendocrine carcinomas (NEC). Abnormal p53-expression is a feature of PD tumours, while expression of chromogranin A (CgA) and somatostatin-receptor 2a (SSTR-2a) may be a feature of well-differentiated tumours. The aim of this study was to elucidate the expression and prognostic value of these three markers in 163 GEP-NEN patients with a Ki67-index > 20{\%}.METHOD: Clinical data, histopathology and overall survival were analysed according to Kaplan-Meier's method and Cox regression. The expression of SSTR-2a, CgA and synaptophysin was analysed in tumour specimens by immunohistochemistry, and semi-quantitatively scored as negative (< 5{\%}), heterogeneously positive (5-30{\%}) or strongly positive (> 30{\%}). P53 was defined as normal when scored as heterogeneously positive (1-30{\%}), and abnormal when negative (0{\%}) or strongly positive (> 30{\%}).RESULTS: In multivariate analysis, better survival was observed among patients with heterogeneously positive p53 compared to strongly positive (p < 0.001). When dichotomised, tumours with a heterogeneously positive p53 vs. negative and strongly positive p53 also showed a significantly better survival (p = 0.002). Survival was significantly worse for negative CgA compared to heterogeneously positive CgA (p = 0.02). Strongly positive SSTR-2a expression was found in 26{\%} of the 163 included patients. Well-differentiated morphology correlated with strong expression of SSTR-2a and CgA, and heterogeneously positive p53-staining, and was more frequent in pancreatic primaries. In pancreatic primaries, strongly positive SSTR-2a was associated with longer survival (univariate analysis, p = 0.02). A significantly lower Ki67 proliferation index was found in patients with a heterogeneously positive p53, a positive SSTR-2a and CgA expression.CONCLUSION: Our results suggest that abnormal p53-expression is an independent negative prognostic marker in GEP-NEN with a Ki67-index > 20{\%}. Patients with heterogeneously positive p53 had the best prognosis. SSTR-2a was a positive prognostic marker in pancreatic NEN. Negative CgA was associated with a significantly worse OS compared to heterogeneously positive CgA-expression in a multivariate sub-analysis. Lower Ki67 index correlated significantly with heterogeneously positive p53, positive SSTR-2a and CgA expression.",
author = "Kirstine Nielsen and Tina Binderup and Langer, {Seppo W} and Andreas Kjaer and Pauline Knigge and Veronica Gr{\o}ndahl and Linea Melchior and Birgitte Federspiel and Ulrich Knigge",
year = "2020",
month = "1",
day = "10",
doi = "10.1186/s12885-019-6498-z",
language = "English",
volume = "20",
pages = "27",
journal = "B M C Cancer",
issn = "1471-2407",
publisher = "BioMed Central Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms

AU - Nielsen, Kirstine

AU - Binderup, Tina

AU - Langer, Seppo W

AU - Kjaer, Andreas

AU - Knigge, Pauline

AU - Grøndahl, Veronica

AU - Melchior, Linea

AU - Federspiel, Birgitte

AU - Knigge, Ulrich

PY - 2020/1/10

Y1 - 2020/1/10

N2 - BACKGROUND: High grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) with a Ki67 proliferation index > 20%, include well-differentiated tumours grade 3 (NET G3) and poorly differentiated (PD) neuroendocrine carcinomas (NEC). Abnormal p53-expression is a feature of PD tumours, while expression of chromogranin A (CgA) and somatostatin-receptor 2a (SSTR-2a) may be a feature of well-differentiated tumours. The aim of this study was to elucidate the expression and prognostic value of these three markers in 163 GEP-NEN patients with a Ki67-index > 20%.METHOD: Clinical data, histopathology and overall survival were analysed according to Kaplan-Meier's method and Cox regression. The expression of SSTR-2a, CgA and synaptophysin was analysed in tumour specimens by immunohistochemistry, and semi-quantitatively scored as negative (< 5%), heterogeneously positive (5-30%) or strongly positive (> 30%). P53 was defined as normal when scored as heterogeneously positive (1-30%), and abnormal when negative (0%) or strongly positive (> 30%).RESULTS: In multivariate analysis, better survival was observed among patients with heterogeneously positive p53 compared to strongly positive (p < 0.001). When dichotomised, tumours with a heterogeneously positive p53 vs. negative and strongly positive p53 also showed a significantly better survival (p = 0.002). Survival was significantly worse for negative CgA compared to heterogeneously positive CgA (p = 0.02). Strongly positive SSTR-2a expression was found in 26% of the 163 included patients. Well-differentiated morphology correlated with strong expression of SSTR-2a and CgA, and heterogeneously positive p53-staining, and was more frequent in pancreatic primaries. In pancreatic primaries, strongly positive SSTR-2a was associated with longer survival (univariate analysis, p = 0.02). A significantly lower Ki67 proliferation index was found in patients with a heterogeneously positive p53, a positive SSTR-2a and CgA expression.CONCLUSION: Our results suggest that abnormal p53-expression is an independent negative prognostic marker in GEP-NEN with a Ki67-index > 20%. Patients with heterogeneously positive p53 had the best prognosis. SSTR-2a was a positive prognostic marker in pancreatic NEN. Negative CgA was associated with a significantly worse OS compared to heterogeneously positive CgA-expression in a multivariate sub-analysis. Lower Ki67 index correlated significantly with heterogeneously positive p53, positive SSTR-2a and CgA expression.

AB - BACKGROUND: High grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) with a Ki67 proliferation index > 20%, include well-differentiated tumours grade 3 (NET G3) and poorly differentiated (PD) neuroendocrine carcinomas (NEC). Abnormal p53-expression is a feature of PD tumours, while expression of chromogranin A (CgA) and somatostatin-receptor 2a (SSTR-2a) may be a feature of well-differentiated tumours. The aim of this study was to elucidate the expression and prognostic value of these three markers in 163 GEP-NEN patients with a Ki67-index > 20%.METHOD: Clinical data, histopathology and overall survival were analysed according to Kaplan-Meier's method and Cox regression. The expression of SSTR-2a, CgA and synaptophysin was analysed in tumour specimens by immunohistochemistry, and semi-quantitatively scored as negative (< 5%), heterogeneously positive (5-30%) or strongly positive (> 30%). P53 was defined as normal when scored as heterogeneously positive (1-30%), and abnormal when negative (0%) or strongly positive (> 30%).RESULTS: In multivariate analysis, better survival was observed among patients with heterogeneously positive p53 compared to strongly positive (p < 0.001). When dichotomised, tumours with a heterogeneously positive p53 vs. negative and strongly positive p53 also showed a significantly better survival (p = 0.002). Survival was significantly worse for negative CgA compared to heterogeneously positive CgA (p = 0.02). Strongly positive SSTR-2a expression was found in 26% of the 163 included patients. Well-differentiated morphology correlated with strong expression of SSTR-2a and CgA, and heterogeneously positive p53-staining, and was more frequent in pancreatic primaries. In pancreatic primaries, strongly positive SSTR-2a was associated with longer survival (univariate analysis, p = 0.02). A significantly lower Ki67 proliferation index was found in patients with a heterogeneously positive p53, a positive SSTR-2a and CgA expression.CONCLUSION: Our results suggest that abnormal p53-expression is an independent negative prognostic marker in GEP-NEN with a Ki67-index > 20%. Patients with heterogeneously positive p53 had the best prognosis. SSTR-2a was a positive prognostic marker in pancreatic NEN. Negative CgA was associated with a significantly worse OS compared to heterogeneously positive CgA-expression in a multivariate sub-analysis. Lower Ki67 index correlated significantly with heterogeneously positive p53, positive SSTR-2a and CgA expression.

U2 - 10.1186/s12885-019-6498-z

DO - 10.1186/s12885-019-6498-z

M3 - Journal article

VL - 20

SP - 27

JO - B M C Cancer

JF - B M C Cancer

SN - 1471-2407

IS - 1

ER -

ID: 59041415