Yamamoto Shinji, Tomita Yasuhiko, Hoshida Yoshihiko, Iizuka Norishige, Kidogami Shinya, Miyata Hiroshi, Takiguchi Shuji, Fujiwara Yoshiyuki, Yasuda Takushi, Yano Masahiko, Nakamori Shoji, Sakon Masato, Monden Morito, Aozasa Katsuyuki
Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Clin Cancer Res. 2004 Aug 15;10(16):5558-65. doi: 10.1158/1078-0432.CCR-0723-03.
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.
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.
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.
This study demonstrated the prognostic significance of VCP expression in ESCC.
食管鳞状细胞癌（ESCC）由于主要通过淋巴管发生全身转移，预后通常较差。含缬酪肽蛋白（VCP）已被证明与抗凋亡功能及通过激活核因子-κB信号通路的转移相关。在本研究中，我们检测了VCP与ESCC复发及预后的相关性。
通过免疫组织化学分析156例ESCC患者[139例男性和17例女性；年龄范围38 - 82岁（中位数60岁）]的VCP表达。肿瘤细胞中的染色强度分为比内皮细胞弱（1级）或等于或强于内皮细胞（2级）。在12例患者中检测了VCP表达在mRNA和蛋白水平之间的相关性。
57例（37.3%）病例显示1级VCP表达，96例（62.7%）显示2级VCP表达。定量逆转录-PCR分析显示2级（n = 6）病例的VCP mRNA表达高于1级病例（n = 6；P < 0.05）。与1级表达的ESCC相比，2级表达的ESCC显示出更高的淋巴结转移率（P < 0.01）和更深的肿瘤浸润率（P < 0.01），以及更差的无病生存率和总生存率（两项分析均P < 0.001）。多因素分析显示VCP表达水平是无病生存和总生存的独立预后因素。此外，VCP水平是早期（pT1）和晚期（pT2 - pT4）阶段组无病生存的指标。
本研究证明了VCP表达在ESCC中的预后意义。
