The Prognostic Value of Mitotic Activity Index (MAI), Phosphohistone H3 (PPH3), Cyclin B1, Cyclin A, and Ki67, Alone and in Combinations, in Node-Negative Premenopausal Breast Cancer.
Klintman, Marie LU ; Forsare, Carina LU
; Ahlin, Cecilia
; Beglerbegovic, Sanda
; Fjällskog, Marie-Louise
; Grabau, Dorthe
LU
; Gudlaugsson, Einar
; Janssen, Emiel A M
; Lövgren, Kristina
LU
and Skaland, Ivar
, et al.
(2013)
In PLoS ONE
8(12).
- Abstract
- Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off ≥10 mitoses), and... (More)
- Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off ≥10 mitoses), and PPH3, cyclin B1, cyclin A, and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable analysis (high versus low) the strongest prognostic proliferation factor for 10-year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A combination variable, with patients with MAI and/or cyclin A high defined as high-risk, had even stronger prognostic value (HR=4.2, 95%CI: 2.2-7). When stratifying for ER-status, MAI was a significant prognostic factor in ER-positive patients only (HR=7.0, 95%CI: 3.1-16). Stratified for histological grade, MAI added prognostic value in grade 2 (HR=7.2, 95%CI: 3.1-38) and grade 1 patients. In multivariable analysis including HER2, age, adjuvant medical treatment, ER, and one proliferation factor at a time, only MAI (HR=2.7, 95%CI: 1.1-6.7), and cyclin A (HR=2.7, 95%CI: 1.2-6.0) remained independently prognostic. In conclusion this study confirms the strong prognostic value of all proliferation factors, especially MAI and cyclin A, in all patients, and more specifically in ER-positive patients, and patients with histological grade 2 and 1. Additionally, by combining two proliferation factors, an even stronger prognostic value may be found. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4224909
- author
- Klintman, Marie
LU
; Forsare, Carina
LU
; Ahlin, Cecilia
; Beglerbegovic, Sanda
; Fjällskog, Marie-Louise
; Grabau, Dorthe
LU
; Gudlaugsson, Einar
; Janssen, Emiel A M
; Lövgren, Kristina
LU
and Skaland, Ivar
, et al. (More)
- Klintman, Marie
LU
; Forsare, Carina
LU
; Ahlin, Cecilia
; Beglerbegovic, Sanda
; Fjällskog, Marie-Louise
; Grabau, Dorthe
LU
; Gudlaugsson, Einar
; Janssen, Emiel A M
; Lövgren, Kristina
LU
; Skaland, Ivar
; Bendahl, Pär-Ola
LU
; Malmström, Per
LU
; Baak, Jan P A
and Fernö, Mårten
LU
(Less)
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 8
- issue
- 12
- article number
- e81902
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000327949300112
- pmid:24324728
- scopus:84891893232
- pmid:24324728
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0081902
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Oncology, MV (013035000), Pathology, (Lund) (013030000)
- id
- c840c909-7c49-4697-a28d-f833d36bc550 (old id 4224909)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24324728?dopt=Abstract
- date added to LUP
- 2016-04-01 14:28:50
- date last changed
- 2022-03-14 06:04:31
@article{c840c909-7c49-4697-a28d-f833d36bc550,
abstract = {{Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off ≥10 mitoses), and PPH3, cyclin B1, cyclin A, and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable analysis (high versus low) the strongest prognostic proliferation factor for 10-year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A combination variable, with patients with MAI and/or cyclin A high defined as high-risk, had even stronger prognostic value (HR=4.2, 95%CI: 2.2-7). When stratifying for ER-status, MAI was a significant prognostic factor in ER-positive patients only (HR=7.0, 95%CI: 3.1-16). Stratified for histological grade, MAI added prognostic value in grade 2 (HR=7.2, 95%CI: 3.1-38) and grade 1 patients. In multivariable analysis including HER2, age, adjuvant medical treatment, ER, and one proliferation factor at a time, only MAI (HR=2.7, 95%CI: 1.1-6.7), and cyclin A (HR=2.7, 95%CI: 1.2-6.0) remained independently prognostic. In conclusion this study confirms the strong prognostic value of all proliferation factors, especially MAI and cyclin A, in all patients, and more specifically in ER-positive patients, and patients with histological grade 2 and 1. Additionally, by combining two proliferation factors, an even stronger prognostic value may be found.}},
author = {{Klintman, Marie and Forsare, Carina and Ahlin, Cecilia and Beglerbegovic, Sanda and Fjällskog, Marie-Louise and Grabau, Dorthe and Gudlaugsson, Einar and Janssen, Emiel A M and Lövgren, Kristina and Skaland, Ivar and Bendahl, Pär-Ola and Malmström, Per and Baak, Jan P A and Fernö, Mårten}},
issn = {{1932-6203}},
language = {{eng}},
number = {{12}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{The Prognostic Value of Mitotic Activity Index (MAI), Phosphohistone H3 (PPH3), Cyclin B1, Cyclin A, and Ki67, Alone and in Combinations, in Node-Negative Premenopausal Breast Cancer.}},
url = {{https://lup.lub.lu.se/search/files/3998935/4438023}},
doi = {{10.1371/journal.pone.0081902}},
volume = {{8}},
year = {{2013}},
}