Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome

Anna Calió, Alberto Zamó, Maurilio Ponzoni, Maria Elisabetta Zanolin, Andrés J M Ferreri, Serena Pedron, Licia Montagna, Claudia Parolini, Vadim E. Fraifeld, Marina Wolfson, Hagai Yanai, Giovanni Pizzolo, Claudio Doglioni, Fabrizio Vinante, Marco Chilosi

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Abstract

Purpose: There is evidence that Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) could display some molecular and morphologic markers of cellular senescence (CS). We hypothesized that CS mechanisms may have potential prognostic relevance in cHL and investigated whether the expression of the well-established CS biomarkers p21CIP1/WAF1 and p16INK4a by HRS cells might be predictive of the probability of event-free survival (EFS). Experimental Design: The study analyzed a retrospective cohort of 147 patients and the results were validated on a cohort of 91 patients independently diagnosed and treated in a different institution. p16INK4a and p21CIP1/WAF1 were categorized as dichotomous variables (or ≤ 30% of HRS cells at diagnosis) and evaluated in univariate and multivariate analysis. Results: Both molecules were independent prognostic factors. A positive staining of one of the two molecules in more than 30% HRS cells predicted a better EFS (P 0.01). p16INK4a/p21CIP1/WAF1 together as a unique categorical variable (both 30%, either 30%, both ≤ 30%) sorted out three prognostic groups with better, intermediate, or worse outcome either overall or within I-II, bulky and advanced stages. The presence or the lack of the robust expression of p21CIP1/WAF1 and/or p16INK4a defined the prognosis in our series. Conclusions: These findings point to (i) the relevance of CS-related mechanisms in cHL, and to (II) the prognostic value of a simple, reproducible, and low-cost immunohistochemical evaluation of p16INK4a and p21CIP1/WAF1 expression.

Original languageEnglish
Pages (from-to)5164-5172
Number of pages9
JournalClinical Cancer Research
Volume21
Issue number22
DOIs
Publication statusPublished - Nov 15 2015

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Cell Aging
Hodgkin Disease
Reed-Sternberg Cells
Disease-Free Survival
Research Design
Multivariate Analysis
Biomarkers
Staining and Labeling
Costs and Cost Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome. / Calió, Anna; Zamó, Alberto; Ponzoni, Maurilio; Zanolin, Maria Elisabetta; Ferreri, Andrés J M; Pedron, Serena; Montagna, Licia; Parolini, Claudia; Fraifeld, Vadim E.; Wolfson, Marina; Yanai, Hagai; Pizzolo, Giovanni; Doglioni, Claudio; Vinante, Fabrizio; Chilosi, Marco.

In: Clinical Cancer Research, Vol. 21, No. 22, 15.11.2015, p. 5164-5172.

Research output: Contribution to journalArticle

Calió, A, Zamó, A, Ponzoni, M, Zanolin, ME, Ferreri, AJM, Pedron, S, Montagna, L, Parolini, C, Fraifeld, VE, Wolfson, M, Yanai, H, Pizzolo, G, Doglioni, C, Vinante, F & Chilosi, M 2015, 'Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome', Clinical Cancer Research, vol. 21, no. 22, pp. 5164-5172. https://doi.org/10.1158/1078-0432.CCR-15-0508
Calió, Anna ; Zamó, Alberto ; Ponzoni, Maurilio ; Zanolin, Maria Elisabetta ; Ferreri, Andrés J M ; Pedron, Serena ; Montagna, Licia ; Parolini, Claudia ; Fraifeld, Vadim E. ; Wolfson, Marina ; Yanai, Hagai ; Pizzolo, Giovanni ; Doglioni, Claudio ; Vinante, Fabrizio ; Chilosi, Marco. / Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 22. pp. 5164-5172.
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abstract = "Purpose: There is evidence that Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) could display some molecular and morphologic markers of cellular senescence (CS). We hypothesized that CS mechanisms may have potential prognostic relevance in cHL and investigated whether the expression of the well-established CS biomarkers p21CIP1/WAF1 and p16INK4a by HRS cells might be predictive of the probability of event-free survival (EFS). Experimental Design: The study analyzed a retrospective cohort of 147 patients and the results were validated on a cohort of 91 patients independently diagnosed and treated in a different institution. p16INK4a and p21CIP1/WAF1 were categorized as dichotomous variables (or ≤ 30{\%} of HRS cells at diagnosis) and evaluated in univariate and multivariate analysis. Results: Both molecules were independent prognostic factors. A positive staining of one of the two molecules in more than 30{\%} HRS cells predicted a better EFS (P 0.01). p16INK4a/p21CIP1/WAF1 together as a unique categorical variable (both 30{\%}, either 30{\%}, both ≤ 30{\%}) sorted out three prognostic groups with better, intermediate, or worse outcome either overall or within I-II, bulky and advanced stages. The presence or the lack of the robust expression of p21CIP1/WAF1 and/or p16INK4a defined the prognosis in our series. Conclusions: These findings point to (i) the relevance of CS-related mechanisms in cHL, and to (II) the prognostic value of a simple, reproducible, and low-cost immunohistochemical evaluation of p16INK4a and p21CIP1/WAF1 expression.",
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T1 - Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome

AU - Calió, Anna

AU - Zamó, Alberto

AU - Ponzoni, Maurilio

AU - Zanolin, Maria Elisabetta

AU - Ferreri, Andrés J M

AU - Pedron, Serena

AU - Montagna, Licia

AU - Parolini, Claudia

AU - Fraifeld, Vadim E.

AU - Wolfson, Marina

AU - Yanai, Hagai

AU - Pizzolo, Giovanni

AU - Doglioni, Claudio

AU - Vinante, Fabrizio

AU - Chilosi, Marco

PY - 2015/11/15

Y1 - 2015/11/15

N2 - Purpose: There is evidence that Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) could display some molecular and morphologic markers of cellular senescence (CS). We hypothesized that CS mechanisms may have potential prognostic relevance in cHL and investigated whether the expression of the well-established CS biomarkers p21CIP1/WAF1 and p16INK4a by HRS cells might be predictive of the probability of event-free survival (EFS). Experimental Design: The study analyzed a retrospective cohort of 147 patients and the results were validated on a cohort of 91 patients independently diagnosed and treated in a different institution. p16INK4a and p21CIP1/WAF1 were categorized as dichotomous variables (or ≤ 30% of HRS cells at diagnosis) and evaluated in univariate and multivariate analysis. Results: Both molecules were independent prognostic factors. A positive staining of one of the two molecules in more than 30% HRS cells predicted a better EFS (P 0.01). p16INK4a/p21CIP1/WAF1 together as a unique categorical variable (both 30%, either 30%, both ≤ 30%) sorted out three prognostic groups with better, intermediate, or worse outcome either overall or within I-II, bulky and advanced stages. The presence or the lack of the robust expression of p21CIP1/WAF1 and/or p16INK4a defined the prognosis in our series. Conclusions: These findings point to (i) the relevance of CS-related mechanisms in cHL, and to (II) the prognostic value of a simple, reproducible, and low-cost immunohistochemical evaluation of p16INK4a and p21CIP1/WAF1 expression.

AB - Purpose: There is evidence that Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) could display some molecular and morphologic markers of cellular senescence (CS). We hypothesized that CS mechanisms may have potential prognostic relevance in cHL and investigated whether the expression of the well-established CS biomarkers p21CIP1/WAF1 and p16INK4a by HRS cells might be predictive of the probability of event-free survival (EFS). Experimental Design: The study analyzed a retrospective cohort of 147 patients and the results were validated on a cohort of 91 patients independently diagnosed and treated in a different institution. p16INK4a and p21CIP1/WAF1 were categorized as dichotomous variables (or ≤ 30% of HRS cells at diagnosis) and evaluated in univariate and multivariate analysis. Results: Both molecules were independent prognostic factors. A positive staining of one of the two molecules in more than 30% HRS cells predicted a better EFS (P 0.01). p16INK4a/p21CIP1/WAF1 together as a unique categorical variable (both 30%, either 30%, both ≤ 30%) sorted out three prognostic groups with better, intermediate, or worse outcome either overall or within I-II, bulky and advanced stages. The presence or the lack of the robust expression of p21CIP1/WAF1 and/or p16INK4a defined the prognosis in our series. Conclusions: These findings point to (i) the relevance of CS-related mechanisms in cHL, and to (II) the prognostic value of a simple, reproducible, and low-cost immunohistochemical evaluation of p16INK4a and p21CIP1/WAF1 expression.

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