Comparing the Prognostic Value of PTEN and Akt Expression with the Mitotic Activity Index in Adjuvant Chemotherapy-Treated Node-Negative Breast Cancer patients aged <55 years

Background: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in invasive breast cancer (IBC) is controversial. Cell proliferation, especially the Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative (LNneg) invasive breast cancer. However, its prognostic value has no...

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Main Authors: Emiel A. M. Janssen, Håvard Søiland, Ivar Skaland, Einar Gudlaugson, Kjell H. Kjellevold, Arne Nysted, Jon-Arne Søreide, Jan P. A. Baak
Format: Article
Language:English
Published: Wiley 2007-01-01
Series:Cellular Oncology
Online Access:http://dx.doi.org/10.1155/2007/569246
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author Emiel A. M. Janssen
Håvard Søiland
Ivar Skaland
Einar Gudlaugson
Kjell H. Kjellevold
Arne Nysted
Jon-Arne Søreide
Jan P. A. Baak
author_facet Emiel A. M. Janssen
Håvard Søiland
Ivar Skaland
Einar Gudlaugson
Kjell H. Kjellevold
Arne Nysted
Jon-Arne Søreide
Jan P. A. Baak
author_sort Emiel A. M. Janssen
collection DOAJ
description Background: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in invasive breast cancer (IBC) is controversial. Cell proliferation, especially the Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative (LNneg) invasive breast cancer. However, its prognostic value has not been compared with the value of Akt and PTEN expression. Material and Methods: Prognostic comparison of Her2Neu, p110alpha (PIK3CA), Akt, mTOR, PTEN, MAI and cell-cycle regulators in 125 LNneg patients aged <55 years with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based adjuvant systemic chemotherapy. Results: Twenty-one (17%) patients developed distant metastases = DMs (median follow-up: 134 months). p110alpha correlated (p = 0.01) with pAkt but only in PTEN-negatives; pAkt correlated (p = 0.02) with mTOR. PTEN-negativity correlated with high MAI, high grade and ER-negativity (p = 0.009). The MAI was the strongest prognosticator (Hazard Ratio = HR = 2.9, p = 0.01). Her2Neu/p110α/Akt/mTOR features have no additional prognostic value to the MAI. PTEN had additional value but only in MAI < 3 (39/125 = 31%; 8% DMs). 19/39 = 49% of the MAI < 3 patients have combined MAI < 3 / PTEN+ with 0% DMs, contrasting 15% DMs in MAI < 3 / PTEN− (p = 0.03). Conclusions: In T1−3N0M0 adjuvant CMF-treated breast cancer patients aged <55 years, MAI was the strongest survival predictor. The PI3K/Akt/mTOR pathway and cell-cycle regulator characteristics had no additional prognostic value, but PTEN has. Patients with combined MAI < 3 & PTEN-positivity had 100% survival. The small subgroup of MAI < 3 patients that died were PTEN-negative.
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spelling doaj-art-c811667cba864472a09db2b8b0d3357c2025-02-03T01:20:53ZengWileyCellular Oncology1570-58701875-86062007-01-01291253510.1155/2007/569246Comparing the Prognostic Value of PTEN and Akt Expression with the Mitotic Activity Index in Adjuvant Chemotherapy-Treated Node-Negative Breast Cancer patients aged <55 yearsEmiel A. M. Janssen0Håvard Søiland1Ivar Skaland2Einar Gudlaugson3Kjell H. Kjellevold4Arne Nysted5Jon-Arne Søreide6Jan P. A. Baak7Department of Pathology, Stavanger University Hospital, Stavanger, NorwayDepartment of Surgery, Stavanger University Hospital, Stavanger, NorwayDepartment of Pathology, Stavanger University Hospital, Stavanger, NorwayDepartment of Pathology, Stavanger University Hospital, Stavanger, NorwayDepartment of Pathology, Stavanger University Hospital, Stavanger, NorwayDepartment of Surgery, Stavanger University Hospital, Stavanger, NorwayDepartment of Surgery, Stavanger University Hospital, Stavanger, NorwayDepartment of Pathology, Stavanger University Hospital, Stavanger, NorwayBackground: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in invasive breast cancer (IBC) is controversial. Cell proliferation, especially the Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative (LNneg) invasive breast cancer. However, its prognostic value has not been compared with the value of Akt and PTEN expression. Material and Methods: Prognostic comparison of Her2Neu, p110alpha (PIK3CA), Akt, mTOR, PTEN, MAI and cell-cycle regulators in 125 LNneg patients aged <55 years with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based adjuvant systemic chemotherapy. Results: Twenty-one (17%) patients developed distant metastases = DMs (median follow-up: 134 months). p110alpha correlated (p = 0.01) with pAkt but only in PTEN-negatives; pAkt correlated (p = 0.02) with mTOR. PTEN-negativity correlated with high MAI, high grade and ER-negativity (p = 0.009). The MAI was the strongest prognosticator (Hazard Ratio = HR = 2.9, p = 0.01). Her2Neu/p110α/Akt/mTOR features have no additional prognostic value to the MAI. PTEN had additional value but only in MAI < 3 (39/125 = 31%; 8% DMs). 19/39 = 49% of the MAI < 3 patients have combined MAI < 3 / PTEN+ with 0% DMs, contrasting 15% DMs in MAI < 3 / PTEN− (p = 0.03). Conclusions: In T1−3N0M0 adjuvant CMF-treated breast cancer patients aged <55 years, MAI was the strongest survival predictor. The PI3K/Akt/mTOR pathway and cell-cycle regulator characteristics had no additional prognostic value, but PTEN has. Patients with combined MAI < 3 & PTEN-positivity had 100% survival. The small subgroup of MAI < 3 patients that died were PTEN-negative.http://dx.doi.org/10.1155/2007/569246
spellingShingle Emiel A. M. Janssen
Håvard Søiland
Ivar Skaland
Einar Gudlaugson
Kjell H. Kjellevold
Arne Nysted
Jon-Arne Søreide
Jan P. A. Baak
Comparing the Prognostic Value of PTEN and Akt Expression with the Mitotic Activity Index in Adjuvant Chemotherapy-Treated Node-Negative Breast Cancer patients aged <55 years
Cellular Oncology
title Comparing the Prognostic Value of PTEN and Akt Expression with the Mitotic Activity Index in Adjuvant Chemotherapy-Treated Node-Negative Breast Cancer patients aged <55 years
title_full Comparing the Prognostic Value of PTEN and Akt Expression with the Mitotic Activity Index in Adjuvant Chemotherapy-Treated Node-Negative Breast Cancer patients aged <55 years
title_fullStr Comparing the Prognostic Value of PTEN and Akt Expression with the Mitotic Activity Index in Adjuvant Chemotherapy-Treated Node-Negative Breast Cancer patients aged <55 years
title_full_unstemmed Comparing the Prognostic Value of PTEN and Akt Expression with the Mitotic Activity Index in Adjuvant Chemotherapy-Treated Node-Negative Breast Cancer patients aged <55 years
title_short Comparing the Prognostic Value of PTEN and Akt Expression with the Mitotic Activity Index in Adjuvant Chemotherapy-Treated Node-Negative Breast Cancer patients aged <55 years
title_sort comparing the prognostic value of pten and akt expression with the mitotic activity index in adjuvant chemotherapy treated node negative breast cancer patients aged 55 years
url http://dx.doi.org/10.1155/2007/569246
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