Kim Wan-Bae, Han Hyung-Joon, Lee Hyun-joo, Park Sung-Soo, Song Tae-Jin, Kim Han-Kyeom, Suh Sung-Ock, Kim Young-Chul, Choi Sang-Yong
Department of Surgery, Korea University Medical College Guro Hospital, 80 Guro-dong, Guro-gu, Seoul, 152-703, South Korea.
Ann Surg Oncol. 2009 Jan;16(1):23-34. doi: 10.1245/s10434-008-0182-x. Epub 2008 Nov 1.
Disruption of cell cycle controls is a pathognomonic feature of all malignant cells. Therefore, we immunohistochemically investigated the relationship between cell cycle regulatory proteins and clinicopathologic features in order to identify the biomarkers related to the outcome of patients with biliary tract cancer (BTC). A cohort of paraffin-embedded specimens were selected from 36 patients, including 18 gallbladder and 18 extrahepatic bile duct cancers, who underwent curative or palliative surgical resection at Korea University Medical Center from June 1998 to December 2004. Tissue microarrays were used to investigate the immunohistochemical staining for p21, p27, p53, cyclin D1, bcl2, and Ki-67. Univariate and multivariate survival analyses were performed to determine the prognostic significance of each protein expression. Absence of p21 expression independently predicted poor outcome in all cases. Well-differentiated tumor was found to be an independent good prognostic factor in gallbladder cancer. Absence of p21 expression and moderately to poorly differentiated tumor were found to be an independent poor prognostic factor in patients with negative for neural invasion. Absence of p21 and bcl2 were found to be an independent poor prognostic factor in patients with no lymph node metastasis. Absence of p21 expression was a significant independent poor prognostic factor in BTC, partly in patients with biologically less aggressive phenotypes. This finding suggests that determination of p21 expression in surgically resected specimens may provide prognostic information in addition to conventional pathologic findings for patients with BTC, especially those who have biologically less aggressive phenotypes.
细胞周期调控的破坏是所有恶性细胞的一个特征性表现。因此，我们采用免疫组化方法研究细胞周期调节蛋白与临床病理特征之间的关系，以确定与胆管癌（BTC）患者预后相关的生物标志物。选取了1998年6月至2004年12月在韩国大学医学中心接受根治性或姑息性手术切除的36例石蜡包埋标本，包括18例胆囊癌和18例肝外胆管癌。使用组织芯片研究p21、p27、p53、细胞周期蛋白D1、bcl2和Ki-67的免疫组化染色。进行单因素和多因素生存分析以确定每种蛋白表达的预后意义。在所有病例中，p21表达缺失独立预测预后不良。高分化肿瘤是胆囊癌独立的良好预后因素。在神经侵犯阴性的患者中，p21表达缺失和中低分化肿瘤是独立的不良预后因素。在无淋巴结转移的患者中，p21和bcl2缺失是独立的不良预后因素。p21表达缺失是BTC的一个显著独立不良预后因素，部分见于生物学侵袭性较低的患者。这一发现表明，对于BTC患者，尤其是那些生物学侵袭性较低的患者，除了传统病理检查结果外，检测手术切除标本中p21的表达可能提供预后信息。
