Clinical Translational Research Received: September 16, 2014 Accepted after revision: October 10, 2014 Published online: February 17, 2015
Oncology DOI: 10.1159/000369073
Expression of Aquaporin-1, Aquaporin-3, and Aquaporin-5 Correlates with Nodal Metastasis in Colon Cancer Byung Woog Kang a Jong Gwang Kim a Soo Jung Lee a Yee Soo Chae a Ji Yun Jeong b Ghil Suk Yoon b Soo Yeun Park c Hye Jin Kim c Jun Seok Park c Gyu-Seog Choi c Ji Yun Jeong d Departments of a Oncology/Hematology, b Pathology, and c Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, and d Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, South Korea
Abstract Objectives: The clinical significance of aquaporin-1 (AQP1), aquaporin-3 (AQP3), and aquaporin-5 (AQP5) expression was analyzed in a large number of patients with colon cancer. Methods: AQP1, AQP3, and AQP5 expression was investigated based on the immunohistochemistry of tissue microarray specimens from 486 colon cancer patients who underwent curative surgery. Scores were given to the staining intensity and percentage of positive cells, and the staining score was defined as the sum of these scores then used to categorize the AQP expression as negative, weakly AQP-positive, or strongly AQP-positive. Results: A total of 298 (61.3%) patients were identified as strongly AQP1-positive (staining score ≥6), while 38 (7.8%) were strongly AQP3-positive and 145 (29.8%) were strongly AQP5-positive. The overexpression of AQP1, AQP3, and AQP5 was significantly correlated with lymph node metastasis in a multivariate logistic analysis (AQP1, p = 0.026; AQP3, p = 0.023; AQP5, p = 0.003). While J.G.K. and G.S.Y. contributed equally to this work.
© 2015 S. Karger AG, Basel 0030–2414/15/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/ocl
the multivariate survival analysis, which included age, histology, TNM stage, and CEA level showed that the expression of AQP1, AQP3, and AQP5 had no effect on the overall survival and disease-free survival. Conclusions: The current study found a significant correlation between AQP1, AQP3, and AQP5 expression and lymph node metastasis in patients with surgically resected colon cancer. © 2015 S. Karger AG, Basel
Introduction
Colon cancer is one of the most important causes of cancer mortality worldwide. Although the benefit of adjuvant chemotherapy in resected colon cancer has already been established by several studies, 20–50% of patients eventually experience tumor recurrence after curative resection followed by chemotherapy, and the effect of adjuvant chemotherapy seems to vary depending on the tumor biology [1]. Therefore, the need for biomarkers has been consistently suggested to discriminate individual Dr. Jong Gwang Kim Kyungpook National University Medical Center 807, Hoguk-ro, Buk-gu Daegu 702-210 (South Korea) E-Mail jkk21c @ knu.ac.kr Dr. Ghil Suk Yoon Kyungpook National University Medical Center 807, Hoguk-ro, Buk-gu Daegu 702-210 (South Korea) E-Mail gsyoon @ knu.ac.kr
Downloaded by: UCSF Library & CKM 169.230.243.252 - 3/4/2015 4:59:09 PM
Key Words Colorectal cancer · Aquaporin · Prognosis
Materials and Methods Patients A total of 486 patients who underwent curative surgery for colon adenocarcinoma at Kyungpook National University Hospital between September 2006 and December 2010 were enrolled in the current study. Based on the 7th edition of AJCC, the pathologic stages after surgical resection were stages I–III. Most of the patients (332 of 486, 68.3%) also received 5-fluorouracil-based adjuvant chemotherapy, while 154 (31.7%) patients had no treatment after surgical resection. This study was approved by the institutional review board at Kyungpook National University Hospital. Tissue Microarray The tissue microarrays (TMAs) were constructed by inserting tumor tissue cores of 2-mm in diameter in a recipient paraffin block. For histologic examination, the 10% formalin-fixed and
2
Oncology DOI: 10.1159/000369073
Table 1. Clinicopathological characteristics of 486 cases of colon
cancer Total (n = 486) Age, years Sex Male Female Primary site of tumor Right Left Pathologic stage I II III T stage T1 T2 T3 T4 N stage N0 N1 N2 Lymphovascular invasion Absence Presence Unknown Perineural invasion Absence Presence Adenocarcinoma histology Well differentiated Moderately differentiated Poorly differentiated Mucinous type CEA level, ng/ml 75%). The AQP1, AQP3, and AQP5 expression in the cancer tissues was defined as the staining score based on the sum of the IS and PC. A staining score of 0–2 was considered AQP-negative, 3–5 as weakly AQP-positive, and 6–7 as strongly AQP-positive. Statistical Analysis The descriptive statistics are reported as proportions and medians. The baseline characteristics and results of the immunohistochemical staining were compared using a χ2 test and logistic regression analysis. The overall survival (OS) time was defined as the interval between the first surgery and death or the last follow-up visit. The disease-free survival (DFS) time was defined as the interval between the first surgery and tumor recurrence or death. The
Clinical Significance of Aquaporins in Colon Cancer
survival rates were estimated using the Kaplan-Meier method, and the survival curves compared using a log-rank test. A multivariate analysis for survival was performed using the Cox proportional hazards regression model. A p value
Oncology DOI: 10.1159/000369073
Expression of Aquaporin-1, Aquaporin-3, and Aquaporin-5 Correlates with Nodal Metastasis in Colon Cancer Byung Woog Kang a Jong Gwang Kim a Soo Jung Lee a Yee Soo Chae a Ji Yun Jeong b Ghil Suk Yoon b Soo Yeun Park c Hye Jin Kim c Jun Seok Park c Gyu-Seog Choi c Ji Yun Jeong d Departments of a Oncology/Hematology, b Pathology, and c Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, and d Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, South Korea
Abstract Objectives: The clinical significance of aquaporin-1 (AQP1), aquaporin-3 (AQP3), and aquaporin-5 (AQP5) expression was analyzed in a large number of patients with colon cancer. Methods: AQP1, AQP3, and AQP5 expression was investigated based on the immunohistochemistry of tissue microarray specimens from 486 colon cancer patients who underwent curative surgery. Scores were given to the staining intensity and percentage of positive cells, and the staining score was defined as the sum of these scores then used to categorize the AQP expression as negative, weakly AQP-positive, or strongly AQP-positive. Results: A total of 298 (61.3%) patients were identified as strongly AQP1-positive (staining score ≥6), while 38 (7.8%) were strongly AQP3-positive and 145 (29.8%) were strongly AQP5-positive. The overexpression of AQP1, AQP3, and AQP5 was significantly correlated with lymph node metastasis in a multivariate logistic analysis (AQP1, p = 0.026; AQP3, p = 0.023; AQP5, p = 0.003). While J.G.K. and G.S.Y. contributed equally to this work.
© 2015 S. Karger AG, Basel 0030–2414/15/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/ocl
the multivariate survival analysis, which included age, histology, TNM stage, and CEA level showed that the expression of AQP1, AQP3, and AQP5 had no effect on the overall survival and disease-free survival. Conclusions: The current study found a significant correlation between AQP1, AQP3, and AQP5 expression and lymph node metastasis in patients with surgically resected colon cancer. © 2015 S. Karger AG, Basel
Introduction
Colon cancer is one of the most important causes of cancer mortality worldwide. Although the benefit of adjuvant chemotherapy in resected colon cancer has already been established by several studies, 20–50% of patients eventually experience tumor recurrence after curative resection followed by chemotherapy, and the effect of adjuvant chemotherapy seems to vary depending on the tumor biology [1]. Therefore, the need for biomarkers has been consistently suggested to discriminate individual Dr. Jong Gwang Kim Kyungpook National University Medical Center 807, Hoguk-ro, Buk-gu Daegu 702-210 (South Korea) E-Mail jkk21c @ knu.ac.kr Dr. Ghil Suk Yoon Kyungpook National University Medical Center 807, Hoguk-ro, Buk-gu Daegu 702-210 (South Korea) E-Mail gsyoon @ knu.ac.kr
Downloaded by: UCSF Library & CKM 169.230.243.252 - 3/4/2015 4:59:09 PM
Key Words Colorectal cancer · Aquaporin · Prognosis
Materials and Methods Patients A total of 486 patients who underwent curative surgery for colon adenocarcinoma at Kyungpook National University Hospital between September 2006 and December 2010 were enrolled in the current study. Based on the 7th edition of AJCC, the pathologic stages after surgical resection were stages I–III. Most of the patients (332 of 486, 68.3%) also received 5-fluorouracil-based adjuvant chemotherapy, while 154 (31.7%) patients had no treatment after surgical resection. This study was approved by the institutional review board at Kyungpook National University Hospital. Tissue Microarray The tissue microarrays (TMAs) were constructed by inserting tumor tissue cores of 2-mm in diameter in a recipient paraffin block. For histologic examination, the 10% formalin-fixed and
2
Oncology DOI: 10.1159/000369073
Table 1. Clinicopathological characteristics of 486 cases of colon
cancer Total (n = 486) Age, years Sex Male Female Primary site of tumor Right Left Pathologic stage I II III T stage T1 T2 T3 T4 N stage N0 N1 N2 Lymphovascular invasion Absence Presence Unknown Perineural invasion Absence Presence Adenocarcinoma histology Well differentiated Moderately differentiated Poorly differentiated Mucinous type CEA level, ng/ml 75%). The AQP1, AQP3, and AQP5 expression in the cancer tissues was defined as the staining score based on the sum of the IS and PC. A staining score of 0–2 was considered AQP-negative, 3–5 as weakly AQP-positive, and 6–7 as strongly AQP-positive. Statistical Analysis The descriptive statistics are reported as proportions and medians. The baseline characteristics and results of the immunohistochemical staining were compared using a χ2 test and logistic regression analysis. The overall survival (OS) time was defined as the interval between the first surgery and death or the last follow-up visit. The disease-free survival (DFS) time was defined as the interval between the first surgery and tumor recurrence or death. The
Clinical Significance of Aquaporins in Colon Cancer
survival rates were estimated using the Kaplan-Meier method, and the survival curves compared using a log-rank test. A multivariate analysis for survival was performed using the Cox proportional hazards regression model. A p value
