caa a22 4500 605490902 CHVBK 20210128100507.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10147-014-0753-8 doi (NATIONALLICENCE)springer-10.1007/s10147-014-0753-8 Extensive analysis of signaling pathway molecules in breast cancer: association with clinicopathological characteristics [Elektronische Daten] [Rie Horii, Masaaki Matsuura, Shingo Dan, Masaru Ushijima, Natsue Uehiro, Akiko Ogiya, Naoko Honma, Yoshinori Ito, Takuji Iwase, Takao Yamori, Futoshi Akiyama] 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-p70S6K, 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 fol lows: p-AKT, 75%; cyclin D1, 12%; P27, 53%; p-p70S6K, 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-p70S6K 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-p70S6K and p-4EBP1, p-p70S6K and p-MAPK/ERK, and between p-4EBP1 and p-MAPK/ERK. Levels of p-p70S6K 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-p70S6K expression may be of use in predicting clinical outcome. Japan Society of Clinical Oncology, 2014 Breast cancer nationallicence Pathology nationallicence Classification nationallicence p-p70S6K nationallicence Signaling pathway nationallicence Survival nationallicence Horii Rie Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, 135-8550, Tokyo, Japan aut Matsuura Masaaki Department of Cancer Genomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan aut Dan Shingo Department of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan aut Ushijima Masaru Bioinformatics Group, Genome Center, Japanese Foundation for Cancer Research, Tokyo, Japan aut Uehiro Natsue Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan aut Ogiya Akiko Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan aut Honma Naoko Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, 135-8550, Tokyo, Japan aut Ito Yoshinori Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan aut Iwase Takuji Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan aut Yamori Takao Department of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan aut Akiyama Futoshi Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, 135-8550, Tokyo, Japan aut International Journal of Clinical Oncology Springer Japan 20/3(2015-06-01), 490-498 1341-9625 20:3<490 2015 20 10147 https://doi.org/10.1007/s10147-014-0753-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-014-0753-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Horii Rie Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, 135-8550, Tokyo, Japan aut NATIONALLICENCE 700 1- Matsuura Masaaki Department of Cancer Genomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan aut NATIONALLICENCE 700 1- Dan Shingo Department of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan aut NATIONALLICENCE 700 1- Ushijima Masaru Bioinformatics Group, Genome Center, Japanese Foundation for Cancer Research, Tokyo, Japan aut NATIONALLICENCE 700 1- Uehiro Natsue Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan aut NATIONALLICENCE 700 1- Ogiya Akiko Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan aut NATIONALLICENCE 700 1- Honma Naoko Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, 135-8550, Tokyo, Japan aut NATIONALLICENCE 700 1- Ito Yoshinori Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan aut NATIONALLICENCE 700 1- Iwase Takuji Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan aut NATIONALLICENCE 700 1- Yamori Takao Department of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan aut NATIONALLICENCE 700 1- Akiyama Futoshi Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, 135-8550, Tokyo, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/3(2015-06-01), 490-498 1341-9625 20:3<490 2015 20 10147