Masami Ito1, Genichiro Ishii2, Kanji Nagai3, Ryo Maeda4, Yasutaka Nakano5, Atsushi Ochiai6. 1. Department of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba; Division of Respiratory Medicine, Department of Medicine, Shiga University of Medical, Science, Otsu, Shiga, Japan. 2. Department of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba. Electronic address: gishii@east.ncc.go.jp. 3. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba. 4. Department of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba. 5. Division of Respiratory Medicine, Department of Medicine, Shiga University of Medical, Science, Otsu, Shiga, Japan. 6. Department of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba.
Abstract
BACKGROUND: The tumor microenvironment, of which cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are the major cellular components, plays an important role in tumor progression. This study evaluated the significance of podoplanin-positive CAFs and CD204-positive TAMs, which may reflect tumor-promoting CAFs and TAMs, as risk factors for recurrence in patients with stage I lung adenocarcinoma. METHODS: The expression of podoplanin in CAFs and CD204 in TAMs was analyzed by immunohistochemistry in 304 patients with stage I lung adenocarcinoma who underwent surgical resection between September 1992 and July 2004. The recurrence-free proportion (RFP) was estimated using the Kaplan-Meier method. RESULTS: The presence of podoplanin-positive CAFs and the higher number of CD204-positive TAMs were associated with a lower 5-year RFP (P < .001 and P = .001, respectively). Podoplanin-positive CAFs were an independently statistically significant risk factor for recurrence with the highest hazard ratio (3.474, P = .029, by multivariate Cox proportional hazards model). According to subgroup analyses combining podoplanin-positive CAFs and other independent risk factors (visceral pleural invasion and intratumoral vascular invasion), the 5-year RFPs were 95.6%, 92.3%, 80.5%, and 30.3% (P = .294, P = .067, and P < .001) for patients with zero, one, two, or three risk factors, respectively. CONCLUSIONS: Podoplanin-positive CAFs were the most powerful independent risk factor for recurrence in patients with stage I lung adenocarcinoma. Podoplanin-positive CAFs may be useful for identifying patients with a high risk of recurrence who might benefit from adjuvant chemotherapy.
BACKGROUND: The tumor microenvironment, of which cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are the major cellular components, plays an important role in tumor progression. This study evaluated the significance of podoplanin-positive CAFs and CD204-positive TAMs, which may reflect tumor-promoting CAFs and TAMs, as risk factors for recurrence in patients with stage I lung adenocarcinoma. METHODS: The expression of podoplanin in CAFs and CD204 in TAMs was analyzed by immunohistochemistry in 304 patients with stage I lung adenocarcinoma who underwent surgical resection between September 1992 and July 2004. The recurrence-free proportion (RFP) was estimated using the Kaplan-Meier method. RESULTS: The presence of podoplanin-positive CAFs and the higher number of CD204-positive TAMs were associated with a lower 5-year RFP (P < .001 and P = .001, respectively). Podoplanin-positive CAFs were an independently statistically significant risk factor for recurrence with the highest hazard ratio (3.474, P = .029, by multivariate Cox proportional hazards model). According to subgroup analyses combining podoplanin-positive CAFs and other independent risk factors (visceral pleural invasion and intratumoral vascular invasion), the 5-year RFPs were 95.6%, 92.3%, 80.5%, and 30.3% (P = .294, P = .067, and P < .001) for patients with zero, one, two, or three risk factors, respectively. CONCLUSIONS:Podoplanin-positive CAFs were the most powerful independent risk factor for recurrence in patients with stage I lung adenocarcinoma. Podoplanin-positive CAFs may be useful for identifying patients with a high risk of recurrence who might benefit from adjuvant chemotherapy.
Authors: Harini Krishnan; Jhon A Ochoa-Alvarez; Yongquan Shen; Evan Nevel; Meenakshi Lakshminarayanan; Mary C Williams; Maria I Ramirez; W Todd Miller; Gary S Goldberg Journal: J Biol Chem Date: 2013-03-25 Impact factor: 5.157
Authors: Silvestre Vicent; Leanne C Sayles; Dedeepya Vaka; Purvesh Khatri; Olivier Gevaert; Ron Chen; Yanyan Zheng; Anna K Gillespie; Nicole Clarke; Yue Xu; Joseph Shrager; Chuong D Hoang; Sylvia Plevritis; Atul J Butte; E Alejandro Sweet-Cordero Journal: Cancer Res Date: 2012-09-07 Impact factor: 12.701
Authors: C J Foley; M Fanjul-Fernández; A Bohm; N Nguyen; A Agarwal; K Austin; G Koukos; L Covic; C López-Otín; A Kuliopulos Journal: Oncogene Date: 2013-05-27 Impact factor: 9.867