Expression level of valosin-containing protein (p97) is associated with prognosis of esophageal carcinoma.
OBJECTIVE
Esophageal squamous cell carcinoma (ESCC) frequently shows a poor prognosis because of the occurrence of systemic metastasis, mainly via lymphatic vessels. Valosin-containing protein (VCP) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, we examined the association of VCP with the recurrence and prognosis of ESCC.


METHODS
VCP expression in 156 ESCC patients [139 males and 17 females; age range, 38-82 (median, 60) years] was analyzed by immunohistochemistry. Staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. The correlation of VCP expression between the mRNA and protein levels was examined in 12 patients.


RESULTS
Fifty-seven (37.3%) cases showed level 1 and 96 (62.7%) level 2 VCP expression. Quantitative reverse transcription-PCR analysis revealed greater VCP mRNA expression in level 2 (n = 6) than level 1 cases (n = 6; P < 0.05). ESCC with level 2 expression showed higher rates of lymph node metastasis (P < 0.01) and deep tumor invasion (P < 0.01), and poorer disease-free and overall survival rates (P < 0.001 for both analyses) than ESCC with level 1 expression. Multivariate analysis revealed that VCP expression level is an independent prognosticator for disease-free and overall survival. Furthermore, VCP level was an indicator for disease-free survival in the early (pT1) and the advanced (pT2-pT4) stage groups.


CONCLUSIONS
This study demonstrated the prognostic significance of VCP expression in ESCC.
Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Shinji
S
Yamamoto
Yasuhiko
Y
Tomita
Yoshihiko
Y
Hoshida
Norishige
N
Iizuka
Shinya
S
Kidogami
Hiroshi
H
Miyata
Shuji
S
Takiguchi
Yoshiyuki
Y
Fujiwara
Takushi
T
Yasuda
Masahiko
M
Yano
Shoji
S
Nakamori
Masato
M
Sakon
Morito
M
Monden
Katsuyuki
K
Aozasa
D000251:Adenosine Triphosphatases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013997:Time Factors; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein