Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

Shinichi Aishima, Yunosuke Nishihara, Tomohiro Iguchi, Kenichi Taguchi, Akinobu Taketomi, Yoshihiko Maehara, Masazumi Tsuneyoshi

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Lymph node metastasis via lymphatic vessels is related with an adverse outcome in many tumors. It is unclear whether lymphatic spread needs the development of the new lymphatic vessels or the expression of lymphangiogenetic factor in intrahepatic cholangiocarcinoma. The aim of this study was to assess the role of lymphangiogenesis, vascular endothelial growth factor-C (VEGF-C) expression, and D2-40-positive myofibroblastic cells for lymphatic spread and patient outcome in 88 cases of intrahepatic cholangiocarcinoma. We also assessed VEGF-C expression in 15 cases of metastatic lymph nodes. There was a significant correlation between lower lymphatic vessel density in the tumor center and positive lymphatic invasion (P=0.0100). Poorly differentiated cholangiocarcinoma showed higher lymphatic vessel density in the tumor periphery and in the peritumoral area (P=0.0315 and P=0.0360, respectively). Lymphatic invasion was observed higher in the peritumoral area (63%, 24/38) and in the tumor periphery (79%, 30/38) than in the tumor center (27%, 9/38). There was no significant correlation between the proliferative lymphatic vessels and pathologic features; however, lymphatic invasion was significantly associated with VEGF-C expression (P=0.0006), and the VEGF-C expression was seen in 12 of 15 cases (80%) of metastatic lymph node. Nodal metastasis was correlated with D2-40-positive myofibroblasts (P=0.0161). VEGF-C expression was an independent prognostic factor by multivariate survival analysis (P=0.0131). Our findings suggest that VEGF-C has an important role in lymphatic invasion via the preexisting lymphatic vessels in the tumor margin, and that lymphangiogenesis does not play a direct role in lymphatic metastasis. D2-40-positive myofibroblasts may contribute to lymphatic metastasis.

Original languageEnglish
Pages (from-to)256-264
Number of pages9
JournalModern Pathology
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 1 2008

Fingerprint

Vascular Endothelial Growth Factor C
Myofibroblasts
Cholangiocarcinoma
Lymphatic Vessels
Lymphangiogenesis
Lymphatic Metastasis
Lymph Nodes
Neoplasms
Lymphatic Vessel Tumors
Neoplasm Metastasis
Survival Analysis
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Aishima, S., Nishihara, Y., Iguchi, T., Taguchi, K., Taketomi, A., Maehara, Y., & Tsuneyoshi, M. (2008). Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma. Modern Pathology, 21(3), 256-264. https://doi.org/10.1038/modpathol.3800985

Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma. / Aishima, Shinichi; Nishihara, Yunosuke; Iguchi, Tomohiro; Taguchi, Kenichi; Taketomi, Akinobu; Maehara, Yoshihiko; Tsuneyoshi, Masazumi.

In: Modern Pathology, Vol. 21, No. 3, 01.03.2008, p. 256-264.

Research output: Contribution to journalArticle

Aishima, S, Nishihara, Y, Iguchi, T, Taguchi, K, Taketomi, A, Maehara, Y & Tsuneyoshi, M 2008, 'Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma', Modern Pathology, vol. 21, no. 3, pp. 256-264. https://doi.org/10.1038/modpathol.3800985
Aishima, Shinichi ; Nishihara, Yunosuke ; Iguchi, Tomohiro ; Taguchi, Kenichi ; Taketomi, Akinobu ; Maehara, Yoshihiko ; Tsuneyoshi, Masazumi. / Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma. In: Modern Pathology. 2008 ; Vol. 21, No. 3. pp. 256-264.
@article{b2a3c327bffd46e2994d01241096ccc6,
title = "Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma",
abstract = "Lymph node metastasis via lymphatic vessels is related with an adverse outcome in many tumors. It is unclear whether lymphatic spread needs the development of the new lymphatic vessels or the expression of lymphangiogenetic factor in intrahepatic cholangiocarcinoma. The aim of this study was to assess the role of lymphangiogenesis, vascular endothelial growth factor-C (VEGF-C) expression, and D2-40-positive myofibroblastic cells for lymphatic spread and patient outcome in 88 cases of intrahepatic cholangiocarcinoma. We also assessed VEGF-C expression in 15 cases of metastatic lymph nodes. There was a significant correlation between lower lymphatic vessel density in the tumor center and positive lymphatic invasion (P=0.0100). Poorly differentiated cholangiocarcinoma showed higher lymphatic vessel density in the tumor periphery and in the peritumoral area (P=0.0315 and P=0.0360, respectively). Lymphatic invasion was observed higher in the peritumoral area (63{\%}, 24/38) and in the tumor periphery (79{\%}, 30/38) than in the tumor center (27{\%}, 9/38). There was no significant correlation between the proliferative lymphatic vessels and pathologic features; however, lymphatic invasion was significantly associated with VEGF-C expression (P=0.0006), and the VEGF-C expression was seen in 12 of 15 cases (80{\%}) of metastatic lymph node. Nodal metastasis was correlated with D2-40-positive myofibroblasts (P=0.0161). VEGF-C expression was an independent prognostic factor by multivariate survival analysis (P=0.0131). Our findings suggest that VEGF-C has an important role in lymphatic invasion via the preexisting lymphatic vessels in the tumor margin, and that lymphangiogenesis does not play a direct role in lymphatic metastasis. D2-40-positive myofibroblasts may contribute to lymphatic metastasis.",
author = "Shinichi Aishima and Yunosuke Nishihara and Tomohiro Iguchi and Kenichi Taguchi and Akinobu Taketomi and Yoshihiko Maehara and Masazumi Tsuneyoshi",
year = "2008",
month = "3",
day = "1",
doi = "10.1038/modpathol.3800985",
language = "English",
volume = "21",
pages = "256--264",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

AU - Aishima, Shinichi

AU - Nishihara, Yunosuke

AU - Iguchi, Tomohiro

AU - Taguchi, Kenichi

AU - Taketomi, Akinobu

AU - Maehara, Yoshihiko

AU - Tsuneyoshi, Masazumi

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Lymph node metastasis via lymphatic vessels is related with an adverse outcome in many tumors. It is unclear whether lymphatic spread needs the development of the new lymphatic vessels or the expression of lymphangiogenetic factor in intrahepatic cholangiocarcinoma. The aim of this study was to assess the role of lymphangiogenesis, vascular endothelial growth factor-C (VEGF-C) expression, and D2-40-positive myofibroblastic cells for lymphatic spread and patient outcome in 88 cases of intrahepatic cholangiocarcinoma. We also assessed VEGF-C expression in 15 cases of metastatic lymph nodes. There was a significant correlation between lower lymphatic vessel density in the tumor center and positive lymphatic invasion (P=0.0100). Poorly differentiated cholangiocarcinoma showed higher lymphatic vessel density in the tumor periphery and in the peritumoral area (P=0.0315 and P=0.0360, respectively). Lymphatic invasion was observed higher in the peritumoral area (63%, 24/38) and in the tumor periphery (79%, 30/38) than in the tumor center (27%, 9/38). There was no significant correlation between the proliferative lymphatic vessels and pathologic features; however, lymphatic invasion was significantly associated with VEGF-C expression (P=0.0006), and the VEGF-C expression was seen in 12 of 15 cases (80%) of metastatic lymph node. Nodal metastasis was correlated with D2-40-positive myofibroblasts (P=0.0161). VEGF-C expression was an independent prognostic factor by multivariate survival analysis (P=0.0131). Our findings suggest that VEGF-C has an important role in lymphatic invasion via the preexisting lymphatic vessels in the tumor margin, and that lymphangiogenesis does not play a direct role in lymphatic metastasis. D2-40-positive myofibroblasts may contribute to lymphatic metastasis.

AB - Lymph node metastasis via lymphatic vessels is related with an adverse outcome in many tumors. It is unclear whether lymphatic spread needs the development of the new lymphatic vessels or the expression of lymphangiogenetic factor in intrahepatic cholangiocarcinoma. The aim of this study was to assess the role of lymphangiogenesis, vascular endothelial growth factor-C (VEGF-C) expression, and D2-40-positive myofibroblastic cells for lymphatic spread and patient outcome in 88 cases of intrahepatic cholangiocarcinoma. We also assessed VEGF-C expression in 15 cases of metastatic lymph nodes. There was a significant correlation between lower lymphatic vessel density in the tumor center and positive lymphatic invasion (P=0.0100). Poorly differentiated cholangiocarcinoma showed higher lymphatic vessel density in the tumor periphery and in the peritumoral area (P=0.0315 and P=0.0360, respectively). Lymphatic invasion was observed higher in the peritumoral area (63%, 24/38) and in the tumor periphery (79%, 30/38) than in the tumor center (27%, 9/38). There was no significant correlation between the proliferative lymphatic vessels and pathologic features; however, lymphatic invasion was significantly associated with VEGF-C expression (P=0.0006), and the VEGF-C expression was seen in 12 of 15 cases (80%) of metastatic lymph node. Nodal metastasis was correlated with D2-40-positive myofibroblasts (P=0.0161). VEGF-C expression was an independent prognostic factor by multivariate survival analysis (P=0.0131). Our findings suggest that VEGF-C has an important role in lymphatic invasion via the preexisting lymphatic vessels in the tumor margin, and that lymphangiogenesis does not play a direct role in lymphatic metastasis. D2-40-positive myofibroblasts may contribute to lymphatic metastasis.

UR - http://www.scopus.com/inward/record.url?scp=39749134727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39749134727&partnerID=8YFLogxK

U2 - 10.1038/modpathol.3800985

DO - 10.1038/modpathol.3800985

M3 - Article

C2 - 18192971

AN - SCOPUS:39749134727

VL - 21

SP - 256

EP - 264

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 3

ER -