Su Jung Shim1, Eunah Shin2, Choong-Sik Lee3, Ja Seung Koo4. 1. Department of Radiation Oncology, Eulji Hospital, Eulji University School of Medicine Seoul, Korea. 2. Department of Pathology, CHA Gangnam Medical Center, CHA University School of Medicine Seoul, Korea. 3. Department of Pathology, Chungnam National University College of Medicine Daejun, Korea. 4. Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.
Abstract
PURPOSE: We evaluated the expression of autotaxin-lysophosphatidate signaling-related proteins and the clinical implications for metastatic breast cancer. METHODS: We constructed tissue microarrays (TMA) with 126 cases of metastatic breast cancer [31 (24.6%) bone metastases, 36 (28.6%) brain metastases, 11 (8.7%) liver metastases, and 48 (38.1%) lung metastasis], and we conducted immunohistochemical staining for the autotoxin-lysophosphatidate signaling-related proteins ATX, LPA1, LPA2, and LPA3. RESULTS: Stromal ATX (P = 0.006) and LPA1 (P < 0.001) were differently expressed according to their metastatic organ; stromal ATX showed high expression in bone metastasis, and LPA1 showed high expression in liver and lung metastases. Stromal ATX positivity was higher than others in luminal A type tumors (P = 0.035), and stromal LPA3 positivity was correlated with a high Ki-67 labeling index (LI) (P = 0.005). In univariate analysis, tumoral LPA3 negativity was correlated with shorter overall survival (OS) (P = 0.015) in metastatic breast cancer. When analyzed according to the metastatic sites, tumoral LPA3 negativity was correlated with shorter OS (P = 0.010) in lung metastasis, whereas stromal LPA3 negativity was correlated with shorter OS (P = 0.026) in brain metastasis. In multivariate Cox analysis, tumoral LPA3 negativity was an independent poor prognostic factor (HR = 2.311, 95% CI: 1.029-5.191, P = 0.043). CONCLUSION: Among autotoxin-lysophosphatidate signaling-related proteins, stromal ATX was highly expressed in bone metastases, and LPA1 was highly expressed in liver and lung metastases. Tumoral LPA3 might be a prognostic factor in metastatic breast cancer. IJCEP
PURPOSE: We evaluated the expression of autotaxin-lysophosphatidate signaling-related proteins and the clinical implications for metastatic breast cancer. METHODS: We constructed tissue microarrays (TMA) with 126 cases of metastatic breast cancer [31 (24.6%) bone metastases, 36 (28.6%) brain metastases, 11 (8.7%) liver metastases, and 48 (38.1%) lung metastasis], and we conducted immunohistochemical staining for the autotoxin-lysophosphatidate signaling-related proteins ATX, LPA1, LPA2, and LPA3. RESULTS: Stromal ATX (P = 0.006) and LPA1 (P < 0.001) were differently expressed according to their metastatic organ; stromal ATX showed high expression in bone metastasis, and LPA1 showed high expression in liver and lung metastases. Stromal ATX positivity was higher than others in luminal A type tumors (P = 0.035), and stromal LPA3 positivity was correlated with a high Ki-67 labeling index (LI) (P = 0.005). In univariate analysis, tumoralLPA3 negativity was correlated with shorter overall survival (OS) (P = 0.015) in metastatic breast cancer. When analyzed according to the metastatic sites, tumoralLPA3 negativity was correlated with shorter OS (P = 0.010) in lung metastasis, whereas stromal LPA3 negativity was correlated with shorter OS (P = 0.026) in brain metastasis. In multivariate Cox analysis, tumoralLPA3 negativity was an independent poor prognostic factor (HR = 2.311, 95% CI: 1.029-5.191, P = 0.043). CONCLUSION: Among autotoxin-lysophosphatidate signaling-related proteins, stromal ATX was highly expressed in bone metastases, and LPA1 was highly expressed in liver and lung metastases. TumoralLPA3 might be a prognostic factor in metastatic breast cancer. IJCEP
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: Shuying Liu; Makiko Umezu-Goto; Mandi Murph; Yiling Lu; Wenbin Liu; Fan Zhang; Shuangxing Yu; L Clifton Stephens; Xiaojiang Cui; George Murrow; Kevin Coombes; William Muller; Mien-Chie Hung; Charles M Perou; Adrian V Lee; Xianjun Fang; Gordon B Mills Journal: Cancer Cell Date: 2009-06-02 Impact factor: 31.743
Authors: Honglu Zhang; Xiaoyu Xu; Joanna Gajewiak; Ryoko Tsukahara; Yuko Fujiwara; Jianxiong Liu; James I Fells; Donna Perygin; Abby L Parrill; Gabor Tigyi; Glenn D Prestwich Journal: Cancer Res Date: 2009-06-09 Impact factor: 12.701
Authors: Jochen Gaedcke; Frank Traub; Simone Milde; Ludwig Wilkens; Alexandru Stan; Helmut Ostertag; Mathias Christgen; Reinhard von Wasielewski; Hans H Kreipe Journal: Mod Pathol Date: 2007-06-01 Impact factor: 7.842