Aberrant expression of pRb and p16INK4a, alone or in combination, indicates poor outcome after resection in patients with colorectal carcinoma

Aberrant expression of pRb and p16INK4a, alone or in combination, indicates poor outcome after resection in patients with colorectal carcinoma
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DOI:
10.1016/j.humpath.2004.06.010
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发表时间:
2004-10-01
期刊:
影响因子:
3.3
通讯作者:
Hatakeyama, K
Hatakeyama, K
中科院分区:
医学3区
文献类型:
--
作者:
Cui, X;Shirai, Y;Hatakeyama, K

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本研究旨在明确视网膜母细胞瘤蛋白(PRB)和p16(INK4a)(P16)在可切除性结直肠癌(CRC)中的表达异常,并评价pRb和p16在结直肠癌患者中的预后意义。自1990年7月至1993年12月,连续117例结直肠癌患者接受根治性切除和根治性淋巴清扫。切除标本用免疫组织化学方法检测pRb和p16的异常表达。回顾分析pRb和p16的表达状况与临床病理特征的关系。用COX比例风险模型确定影响术后生存的独立因素。中位随访时间为62个月。PRb和p16的异常表达分别为82例(70%)和87例(74%)。61例(52%)患者出现这些蛋白的一致异常。PRb表达缺失与肿瘤部位相关(P=0.0119),p16过表达与肿瘤大小相关(P=0.0034)。PRb、p16蛋白表达异常与肿瘤分期有关(P=0.011)。PRb和/或p16异常表达患者术后预后较pRb和p16正常表达患者差(pRb,P=0.0151;p16,P=0.0247)。PRb和p16同时异常提示患者生存最差(P=0.0310)。PRb和p16的异常表达独立影响术后生存率(相对危险度=6.312,P
This study aimed to identify potential abnormalities of retinoblastoma protein (pRb) and p16(INK4a) (p16) expression in resectable colorectal carcinomas (CRCs) and to assess the prognostic significance of pRb and p 16 levels in patients with CRC. From July 1990 through December 1993, 117 consecutive patients with CRC underwent curative resection with radical lymphadenectomy. The resected specimens were examined immunohistochemically using monoclonal antibodies to identify abnormalities of pRb and p16 expression. The association of pRb and p16 expression status with clinicopathologic features was analyzed retrospectively. The Cox proportional hazards model was used to identify factors independently affecting survival after resection. The median follow-up period was 62 months. Aberrant expression of pRb and p16 was identified in 82 (70%) and 87 (74%) patients, respectively. Coincident abnormalities of these proteins occurred in 61 (52%) patients. Loss of pRb expression correlated with tumor site (P = 0.0119), whereas p16 overexpression correlated with tumor size (P = 0.0034). Coincident abnormalities of pRb and p16 were associated with TNM tumor stage (P = 0.011). The outcome after resection was worse in patients with aberrant expression of pRb and/or p16 than in patients with normally expressed pRb and p16 (for pRb, P = 0.0151; for p16, P = 0.0247). Coincident abnormalities of pRb and p 16 indicated the worst patient survival (P = 0.0310). Aberrant expression of pRb and p16 independently affected postresection survival (relative risk = 6.312, P