Hyungjin Rhee1, Taek Chung2,3, Jeong Eun Yoo2, Ji Hae Nahm2, Ha Young Woo2, Gi Hong Choi4, Dai Hoon Han4, Young Nyun Park5,6. 1. Department of Radiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. 2. Department of Pathology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. 3. Department of Biomedical Systems Informatics, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. 4. Department of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. 5. Department of Pathology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. young0608@yuhs.ac. 6. BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. young0608@yuhs.ac.
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is subclassified into five gross types, namely, vaguely nodular (VN), single nodular (SN), single nodular with extranodular growth (SNEG), confluent multinodular (CM), and infiltrative (INF) type. However, the pathological background underlying differences in biological behavior of different gross types of HCC remains unclear. METHODS: The histopathological features, clinical outcomes of HCC gross types, and their relationships with stemness-related marker status and fibrotic/hypoxic tumor microenvironment (TME) were evaluated in 266 resected HCCs. The stemness-related markers (CD24, CD44, CD133, SALL4, YAP1, K19 and EpCAM), fibrous tumor stroma (αSMA), and hypoxia (CAIX) were evaluated with immunohistochemistry. RESULTS: Poorer differentiation, reduced capsule formation, higher microvascular invasion, larger tumor size and larger area of necrosis were observed in order of VN-SN-SNEG-CM-INF type (p = 0.005 for all, linear-by-linear association). The expression of summed stemness-related markers and hypoxic/fibrotic TME showed an increasing trend in order of VN-SN-SNEG-CM-INF type (p < 0.005), and their expression well correlated with each other. INF type was found only in HCCs with hypoxic/fibrotic TME or high expression of stemness-related markers. CAIX expression and tumor necrosis ≥ 30% were independent prognostic markers for disease-specific survival. Early recurrence-free survival showed a significant difference based on gross types, revealing best outcome with VN type and worst outcome with INF type. CONCLUSION: The marker expression of stemness-related and hypoxic/fibrotic TME of HCC showed an increasing trend in order of VN-SN-SNEG-CM-INF gross types, and their cross-talk may be involved in the determination of various gross-morphological features and their distinct biological behavior.
BACKGROUND:Hepatocellular carcinoma (HCC) is subclassified into five gross types, namely, vaguely nodular (VN), single nodular (SN), single nodular with extranodular growth (SNEG), confluent multinodular (CM), and infiltrative (INF) type. However, the pathological background underlying differences in biological behavior of different gross types of HCC remains unclear. METHODS: The histopathological features, clinical outcomes of HCC gross types, and their relationships with stemness-related marker status and fibrotic/hypoxic tumor microenvironment (TME) were evaluated in 266 resected HCCs. The stemness-related markers (CD24, CD44, CD133, SALL4, YAP1, K19 and EpCAM), fibrous tumor stroma (αSMA), and hypoxia (CAIX) were evaluated with immunohistochemistry. RESULTS: Poorer differentiation, reduced capsule formation, higher microvascular invasion, larger tumor size and larger area of necrosis were observed in order of VN-SN-SNEG-CM-INF type (p = 0.005 for all, linear-by-linear association). The expression of summed stemness-related markers and hypoxic/fibrotic TME showed an increasing trend in order of VN-SN-SNEG-CM-INF type (p < 0.005), and their expression well correlated with each other. INF type was found only in HCCs with hypoxic/fibrotic TME or high expression of stemness-related markers. CAIX expression and tumor necrosis ≥ 30% were independent prognostic markers for disease-specific survival. Early recurrence-free survival showed a significant difference based on gross types, revealing best outcome with VN type and worst outcome with INF type. CONCLUSION: The marker expression of stemness-related and hypoxic/fibrotic TME of HCC showed an increasing trend in order of VN-SN-SNEG-CM-INF gross types, and their cross-talk may be involved in the determination of various gross-morphological features and their distinct biological behavior.
Authors: Haeryoung Kim; Gi Hong Choi; Deuk Chae Na; Ei Young Ahn; Gwang Il Kim; Jae Eun Lee; Jai Young Cho; Jeong Eun Yoo; Jin Sub Choi; Young Nyun Park Journal: Hepatology Date: 2011-11 Impact factor: 17.425
Authors: M Shimada; T Rikimaru; T Hamatsu; Y Yamashita; T Terashi; K Taguchi; S Tanaka; K Shirabe; K Sugimachi Journal: Am J Surg Date: 2001-08 Impact factor: 2.565
Authors: Eunice Yuen Ting Lau; Jessica Lo; Bowie Yik Ling Cheng; Mark Kin Fai Ma; Joyce Man Fong Lee; Johnson Kai Yu Ng; Stella Chai; Chi Ho Lin; Suk Ying Tsang; Stephanie Ma; Irene Oi Lin Ng; Terence Kin Wah Lee Journal: Cell Rep Date: 2016-04-28 Impact factor: 9.423
Authors: Hyungjin Rhee; Ji Hae Nahm; Haeryoung Kim; Gi Hong Choi; Jeong Eun Yoo; Hye Sun Lee; Myoung Ju Koh; Young Nyun Park Journal: Mod Pathol Date: 2016-06-17 Impact factor: 7.842