Expression of smooth muscle calponin in tumor vessels of human hepatocellular carcinoma and its possible association with prognosis.
BACKGROUND
Hepatocellular carcinoma (HCC) is a vascular-rich tumor. The tumor vessels in HCC were demonstrated to have alpha-smooth muscle actin positive smooth muscle cells (SMCs). However, it is unclear whether the SMCs in the wall of the tumor vessels are differentiated or undifferentiated. Basic calponin is an actin-, tropomyosin-, and calmodulin-binding protein, and expression of the calponin gene in SMCs has been recognized as one of the late stage differentiation markers of SMCs. The authors investigated the differentiation state of SMCs in tumor vessels by immunohistochemical examination of calponin in patients with HCC, and whether it is associated with the patients' prognosis.


METHODS
Tumor and nontumor tissues were obtained from 75 patients with HCC who underwent radical hepatic resection. The differentiation state of the smooth muscle cells were evaluated based on the expression level of calponin, an actin-binding protein, using immunohistochemistry and reverse transcription-polymerase chain reaction analysis. The disease free survival (DFS) rates were estimated according to the Kaplan-Meier method comparing groups of patients with calponin positive and negative tumor vessels. A multivariate analysis based on the Cox proportional hazards regression model was performed to estimate whether the expression of calponin is an independent prognostic factor.


RESULTS
In the 75 patients with HCC examined, 36 patients (48%) possessed calponin positive SMCs, and the remaining 39 (52%) did not. There were no significant differences in either clinical or pathologic factors between the two groups of patients. The 5- and 8-year DFS rate of the patients with calponin positive vessels were 37% and 26%, respectively. These values were significantly higher (11% and 5%) than those of patients with calponin negative vessels. Gender, TNM classification, perioperative transfusion, and calponin expression were found to be independent prognostic factors for DFS.


CONCLUSIONS
Immunohistochemical examination of the calponin expression in the tumor vessels is a new and useful means to predict the prognosis of HCC patients after hepatic resection.
Sasaki
Yo
Y
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan. sasaki-yo@mc.pref.osaka.jp
Yamamura
Hisako
H
Kawakami
Yuriko
Y
Yamada
Terumasa
T
Hiratsuka
Masahiro
M
Kameyama
Masao
M
Ohigashi
Hiroaki
H
Ishikawa
Osamu
O
Imaoka
Shingi
S
Ishiguro
Shingo
S
Takahashi
Katsuhito
K
D000368:Aged; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000096985:Calponins
D002135:Calcium-Binding Proteins; D004273:DNA, Neoplasm; D008840:Microfilament Proteins; D000096985:Calponins