The clinicopathologic significance of the expression of vascular endothelial growth factor-C in intrahepatic cholangiocarcinoma.
OBJECTIVE
Vascular endothelial growth factor-C (VEGF-C) is known to be an important lymphangiogenetic factor. Lymphatic spread is a key prognostic factor in intrahepatic cholangiocarcinoma (ICC). We studied the expression of VEGF-C in ICC tissues to clarify its clinicopathologic significance.


METHODS
The expression of VEGF-C in surgical specimens obtained from 36 patients with ICC who underwent hepatic resection was examined by immunohistochemistry and Western blotting. Strong staining was defined as the presence of VEGF-C immunoreactivity in at least 50% of the tumor cells. Immunoreactivity in approximately 10% to approximately 50% of the tumor cells was considered as weak staining, and less than 10% as no staining.


RESULTS
Of the 36 patients with ICC, 15 patients (41.7%) showed a strong positive result for VEGF-C. Eleven cases (30.6%) were negative and 10 cases (27.8%) showed weak immunoreactivity. VEGF-C expression was significantly correlated with lymph node metastasis (P = 0.032) and positive surgical margin (P = 0.03). Patients who had strong positive staining for VEGF-C showed significantly less favorable survival rates compared with patients who had negative or weak staining (P < 0.01). Other significant prognostic factors by univariate analysis were vascular invasion, lymph node involvement, and positive surgical margin. Multivariate analysis demonstrated that strong VEGF-C expression (P = 0.028) and vascular invasion (P = 0.021) were independent factors indicating poor prognosis.


CONCLUSIONS
Our data suggest that VEGF-C expression serves as an independent and important prognostic factor in ICC patients, and it may play an important role in the lymph node metastasis of ICC.
Park
Byung Kyu
BK
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Paik
Yong-Han
YH
Park
Jeong Youp
JY
Park
Kyung Hwa
KH
Bang
Seungmin
S
Park
Seung Woo
SW
Chung
Jae Bock
JB
Park
Young Nyun
YN
Song
Si Young
SY
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016019:Survival Analysis; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C