Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis.
OBJECTIVE
Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. The present study was designed to investigate the prognostic significance of VCP expression in colorectal adenocarcinoma.


METHODS
We analyzed VCP expression immunohistochemically in 129 patients with colorectal carcinoma ages 35-84 years. The staining intensity of tumor cells was categorized as either weaker-to-equal (low VCP expression) or stronger (high expression) than that in noncancerous colonic mucosa. We also analyzed 8 colorectal adenomas and 10 metastatic foci.


RESULTS
Low VCP expression was noted in 41 (31.8%) cases and high expression in 88 (68.2%) cases. A low level of VCP expression was noted in all adenomas, whereas a high level was seen in all metastatic tumors. A significant difference was observed in depth of invasion (T(1-2) versus T(3-4), P < 0.05), presence or absence of venous invasion (P < 0.05), and tumor stage (I and II versus III and IV; P < 0.05) between adenocarcinomas with low and high VCP expression. Patients with high VCP-expressing tumors had a higher recurrence rate (P < 0.001) and poorer disease-free and overall survival (P < 0.01 and P < 0.05, respectively) compared with the low expression group. Multivariate analysis revealed VCP expression level to be an independent prognosticator for both disease-free and overall survival. VCP level was an indicator of disease-free survival in both stage II and III (pathological Tumor-Node-Metastasis classification, P < 0.05 and <0.01, respectively).


CONCLUSIONS
A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.
Yamamoto
Shinji
S
Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Tomita
Yasuhiko
Y
Hoshida
Yoshihiko
Y
Sakon
Masato
M
Kameyama
Masao
M
Imaoka
Shingi
S
Sekimoto
Mitsugu
M
Nakamori
Shoji
S
Monden
Morito
M
Aozasa
Katsuyuki
K
D000236:Adenoma / Q000473:pathology; D000251:Adenosine Triphosphatases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002277:Carcinoma / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D015999:Multivariate Analysis; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis; D011379:Prognosis; D012008:Recurrence; D015398:Signal Transduction; D013997:Time Factors; D016896:Treatment Outcome; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D016328:NF-kappa B; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein