Immunohistochemical Evaluation of Minichromosome Maintenance Protein 7 (MCM7), Topoisomerase IIα, and Ki-67 in Diffuse Malignant Peritoneal Mesothelioma Patients Using Tissue Microarray

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Abstract

Purpose: Immunohistochemistry and tissue microarray (TMA) were used to perform a prognostic analysis of markers related to cell proliferation in diffuse malignant peritoneal mesothelioma (DMPM). Methods: Clinicopathologic data were extracted from a prospectively collected database containing cases of peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the National Cancer Institute of Milan from 1995 to 2013. Eighty-one DMPM patients were recruited and their tissue samples were used to construct TMAs. We evaluated the immunoexpressions of markers related to cell proliferation—topoisomerase IIα, minichromosome maintenance protein 7 (MCM7), and Ki-67—and then conducted a multivariate Cox model to identify the predictors of overall survival (OS) and progression-free survival (PFS) among the following parameters: age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, baseline serum albumin, Charlson Comorbidity Index, previous systemic chemotherapy, histological subtype (epithelioid vs. biphasic/sarcomatoid), peritoneal cancer index, completeness of cytoreduction (CC), and proliferative biological markers. Results: The rates of high/intermediate immunoreactivity were 95 % for topoisomerase IIα and 90 % for MCM7, and the median Ki-67 labeling index was 5 %. The independent predictors of OS were baseline serum albumin >3.5 g/dl, CC, and Ki-67 >5 %, whereas those for PFS were an ECOG performance status of 0, baseline serum albumin >3.5 g/dl, Charlson Comorbidity Index >3, previous systemic chemotherapy, morbidity G3–5, and Ki-67 >5 %. The remaining biological markers were not associated with outcome. Conclusions: Ki-67 was found to be a new powerful determinant of outcome. Patients with a Ki-67 labeling index >5 % carry a very poor prognosis and do not benefit from the combined procedure. Further studies should be conducted to confirm the present data.

Original languageEnglish
Pages (from-to)4344-4351
Number of pages8
JournalAnnals of Surgical Oncology
Volume22
Issue number13
DOIs
Publication statusPublished - Dec 1 2015

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Minichromosome Maintenance Proteins
Type II DNA Topoisomerase
Serum Albumin
Drug Therapy
Disease-Free Survival
Comorbidity
Biomarkers
Survival
National Cancer Institute (U.S.)
Mesothelioma
Proportional Hazards Models
Immunohistochemistry
Cell Proliferation
Databases
Morbidity
Malignant Mesothelioma
Neoplasms

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

@article{d3d45d00e9fb48a4b181ae89e2c68205,
title = "Immunohistochemical Evaluation of Minichromosome Maintenance Protein 7 (MCM7), Topoisomerase IIα, and Ki-67 in Diffuse Malignant Peritoneal Mesothelioma Patients Using Tissue Microarray",
abstract = "Purpose: Immunohistochemistry and tissue microarray (TMA) were used to perform a prognostic analysis of markers related to cell proliferation in diffuse malignant peritoneal mesothelioma (DMPM). Methods: Clinicopathologic data were extracted from a prospectively collected database containing cases of peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the National Cancer Institute of Milan from 1995 to 2013. Eighty-one DMPM patients were recruited and their tissue samples were used to construct TMAs. We evaluated the immunoexpressions of markers related to cell proliferation—topoisomerase IIα, minichromosome maintenance protein 7 (MCM7), and Ki-67—and then conducted a multivariate Cox model to identify the predictors of overall survival (OS) and progression-free survival (PFS) among the following parameters: age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, baseline serum albumin, Charlson Comorbidity Index, previous systemic chemotherapy, histological subtype (epithelioid vs. biphasic/sarcomatoid), peritoneal cancer index, completeness of cytoreduction (CC), and proliferative biological markers. Results: The rates of high/intermediate immunoreactivity were 95 {\%} for topoisomerase IIα and 90 {\%} for MCM7, and the median Ki-67 labeling index was 5 {\%}. The independent predictors of OS were baseline serum albumin >3.5 g/dl, CC, and Ki-67 >5 {\%}, whereas those for PFS were an ECOG performance status of 0, baseline serum albumin >3.5 g/dl, Charlson Comorbidity Index >3, previous systemic chemotherapy, morbidity G3–5, and Ki-67 >5 {\%}. The remaining biological markers were not associated with outcome. Conclusions: Ki-67 was found to be a new powerful determinant of outcome. Patients with a Ki-67 labeling index >5 {\%} carry a very poor prognosis and do not benefit from the combined procedure. Further studies should be conducted to confirm the present data.",
author = "Marcello Deraco and Antonello Cabras and Dario Baratti and Shigeki Kusamura",
year = "2015",
month = "12",
day = "1",
doi = "10.1245/s10434-015-4498-z",
language = "English",
volume = "22",
pages = "4344--4351",
journal = "Annals of Surgical Oncology",
issn = "1068-9265",
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number = "13",

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TY - JOUR

T1 - Immunohistochemical Evaluation of Minichromosome Maintenance Protein 7 (MCM7), Topoisomerase IIα, and Ki-67 in Diffuse Malignant Peritoneal Mesothelioma Patients Using Tissue Microarray

AU - Deraco, Marcello

AU - Cabras, Antonello

AU - Baratti, Dario

AU - Kusamura, Shigeki

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Purpose: Immunohistochemistry and tissue microarray (TMA) were used to perform a prognostic analysis of markers related to cell proliferation in diffuse malignant peritoneal mesothelioma (DMPM). Methods: Clinicopathologic data were extracted from a prospectively collected database containing cases of peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the National Cancer Institute of Milan from 1995 to 2013. Eighty-one DMPM patients were recruited and their tissue samples were used to construct TMAs. We evaluated the immunoexpressions of markers related to cell proliferation—topoisomerase IIα, minichromosome maintenance protein 7 (MCM7), and Ki-67—and then conducted a multivariate Cox model to identify the predictors of overall survival (OS) and progression-free survival (PFS) among the following parameters: age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, baseline serum albumin, Charlson Comorbidity Index, previous systemic chemotherapy, histological subtype (epithelioid vs. biphasic/sarcomatoid), peritoneal cancer index, completeness of cytoreduction (CC), and proliferative biological markers. Results: The rates of high/intermediate immunoreactivity were 95 % for topoisomerase IIα and 90 % for MCM7, and the median Ki-67 labeling index was 5 %. The independent predictors of OS were baseline serum albumin >3.5 g/dl, CC, and Ki-67 >5 %, whereas those for PFS were an ECOG performance status of 0, baseline serum albumin >3.5 g/dl, Charlson Comorbidity Index >3, previous systemic chemotherapy, morbidity G3–5, and Ki-67 >5 %. The remaining biological markers were not associated with outcome. Conclusions: Ki-67 was found to be a new powerful determinant of outcome. Patients with a Ki-67 labeling index >5 % carry a very poor prognosis and do not benefit from the combined procedure. Further studies should be conducted to confirm the present data.

AB - Purpose: Immunohistochemistry and tissue microarray (TMA) were used to perform a prognostic analysis of markers related to cell proliferation in diffuse malignant peritoneal mesothelioma (DMPM). Methods: Clinicopathologic data were extracted from a prospectively collected database containing cases of peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the National Cancer Institute of Milan from 1995 to 2013. Eighty-one DMPM patients were recruited and their tissue samples were used to construct TMAs. We evaluated the immunoexpressions of markers related to cell proliferation—topoisomerase IIα, minichromosome maintenance protein 7 (MCM7), and Ki-67—and then conducted a multivariate Cox model to identify the predictors of overall survival (OS) and progression-free survival (PFS) among the following parameters: age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, baseline serum albumin, Charlson Comorbidity Index, previous systemic chemotherapy, histological subtype (epithelioid vs. biphasic/sarcomatoid), peritoneal cancer index, completeness of cytoreduction (CC), and proliferative biological markers. Results: The rates of high/intermediate immunoreactivity were 95 % for topoisomerase IIα and 90 % for MCM7, and the median Ki-67 labeling index was 5 %. The independent predictors of OS were baseline serum albumin >3.5 g/dl, CC, and Ki-67 >5 %, whereas those for PFS were an ECOG performance status of 0, baseline serum albumin >3.5 g/dl, Charlson Comorbidity Index >3, previous systemic chemotherapy, morbidity G3–5, and Ki-67 >5 %. The remaining biological markers were not associated with outcome. Conclusions: Ki-67 was found to be a new powerful determinant of outcome. Patients with a Ki-67 labeling index >5 % carry a very poor prognosis and do not benefit from the combined procedure. Further studies should be conducted to confirm the present data.

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