BACKGROUND: The aim of this study was to extensively analyze the signaling pathway molecules in breast cancer and to explore candidate biomarkers for clinicopathological relevance. METHODS: We assessed the expression of key factors in cell signaling, namely p-AKT, cyclin D1, P27, p-p70S6 K, p-4EBP1, and p-MAPK/ERK, within 338 invasive breast cancer patients. These factors were immunohistochemically examined in tumor tissues and assessed by staining score. Staining scores were analyzed by a clustering method to devise a new classification based on pathway activity. We investigated the relationships among staining scores, the clustering classification, and patient characteristics. RESULTS: The proportion of patients displaying high expression levels were as follows: p-AKT, 75%; cyclin D1, 12%; P27, 53%; p-p70S6 K, 37%; p-4EBP1, 19%; and p-MAPK/ERK, 3%. Patients were classified into two groups on the basis of staining scores. Group 1 (39%) included more positive cases for p-4EBP1, p-MAPK/ERK, and p-p70S6 K and fewer positive cases for P27 and cyclin D1 than Group 2 (61%). The clustering classification was significantly related to subgrouping by hormone receptor and HER2 (P < 0.001), nuclear grade (P < 0.001) and histological subtype (P = 0.034). A strong positive correlation was identified between p-AKT and P27, cyclin D1 and P27, p-p70S6 K and p-4EBP1, p-p70S6 K and p-MAPK/ERK, and between p-4EBP1 and p-MAPK/ERK. Levels of p-p70S6 K were significantly related to recurrence in both univariate (RR = 0.75, P < 0.001) and multivariate (RR = 0.71, P = 0.049) analyses. CONCLUSIONS: The present study helps us to understand the characteristics of signaling pathway status in breast cancers. Moreover, p-p70S6 K expression may be of use in predicting clinical outcome.
BACKGROUND: The aim of this study was to extensively analyze the signaling pathway molecules in breast cancer and to explore candidate biomarkers for clinicopathological relevance. METHODS: We assessed the expression of key factors in cell signaling, namely p-AKT, cyclin D1, P27, p-p70S6 K, p-4EBP1, and p-MAPK/ERK, within 338 invasive breast cancerpatients. These factors were immunohistochemically examined in tumor tissues and assessed by staining score. Staining scores were analyzed by a clustering method to devise a new classification based on pathway activity. We investigated the relationships among staining scores, the clustering classification, and patient characteristics. RESULTS: The proportion of patients displaying high expression levels were as follows: p-AKT, 75%; cyclin D1, 12%; P27, 53%; p-p70S6 K, 37%; p-4EBP1, 19%; and p-MAPK/ERK, 3%. Patients were classified into two groups on the basis of staining scores. Group 1 (39%) included more positive cases for p-4EBP1, p-MAPK/ERK, and p-p70S6 K and fewer positive cases for P27 and cyclin D1 than Group 2 (61%). The clustering classification was significantly related to subgrouping by hormone receptor and HER2 (P < 0.001), nuclear grade (P < 0.001) and histological subtype (P = 0.034). A strong positive correlation was identified between p-AKT and P27, cyclin D1 and P27, p-p70S6 K and p-4EBP1, p-p70S6 K and p-MAPK/ERK, and between p-4EBP1 and p-MAPK/ERK. Levels of p-p70S6 K were significantly related to recurrence in both univariate (RR = 0.75, P < 0.001) and multivariate (RR = 0.71, P = 0.049) analyses. CONCLUSIONS: The present study helps us to understand the characteristics of signaling pathway status in breast cancers. Moreover, p-p70S6 K expression may be of use in predicting clinical outcome.
Authors: Ugur Akar; Bulent Ozpolat; Kapil Mehta; Gabriel Lopez-Berestein; Dongwei Zhang; Naoto T Ueno; Gabriel N Hortobagyi; Banu Arun Journal: Mol Cancer Ther Date: 2010-04-27 Impact factor: 6.261
Authors: Maria Stendahl; Sofie Nilsson; Caroline Wigerup; Karin Jirström; Per Ebbe Jönsson; Olle Stål; Göran Landberg Journal: Int J Cancer Date: 2010-12-15 Impact factor: 7.396
Authors: Mohammed A Aleskandarany; Emad A Rakha; Mohamed A Ahmed; Desmond G Powe; Ian O Ellis; Andrew R Green Journal: Breast Cancer Res Treat Date: 2010-07-09 Impact factor: 4.872
Authors: Antonio C Wolff; M Elizabeth H Hammond; Jared N Schwartz; Karen L Hagerty; D Craig Allred; Richard J Cote; Mitchell Dowsett; Patrick L Fitzgibbons; Wedad M Hanna; Amy Langer; Lisa M McShane; Soonmyung Paik; Mark D Pegram; Edith A Perez; Michael F Press; Anthony Rhodes; Catharine Sturgeon; Sheila E Taube; Raymond Tubbs; Gail H Vance; Marc van de Vijver; Thomas M Wheeler; Daniel F Hayes Journal: J Clin Oncol Date: 2006-12-11 Impact factor: 44.544
Authors: Kristine S Klos; Shannon L Wyszomierski; Menghong Sun; Ming Tan; Xiaoyan Zhou; Ping Li; Wentao Yang; Guosheng Yin; Walter N Hittelman; Dihua Yu Journal: Cancer Res Date: 2006-02-15 Impact factor: 12.701
Authors: J A van der Hage; L J C M van den Broek; C Legrand; P C Clahsen; C J A Bosch; E C Robanus-Maandag; C J H van de Velde; M J van de Vijver Journal: Br J Cancer Date: 2004-04-19 Impact factor: 7.640
Authors: Dinja T Kruger; Mark Opdam; Joyce Sanders; Vincent van der Noort; Epie Boven; Sabine C Linn Journal: APMIS Date: 2020-02-27 Impact factor: 3.205