Prognostic value of p16 in locally advanced prostate cancer: A study based on Radiation Therapy Oncology Group protocol 9202
Prognostic value of p16 in locally advanced prostate cancer: A study based on Radiation Therapy Oncology Group protocol 9202
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DOI：
10.1200/jco.2006.08.4152
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发表时间：
2007-07-20
影响因子：
45.3
通讯作者：
Shipley, William
中科院分区：
文献类型：
--
作者：
Chakravarti, Arnab;DeSilvio, Michelle;Shipley, William
目的视网膜母细胞瘤（RB）通路的失调在几乎所有已知的人类肿瘤中都很常见。p16， RB的上游调节因子，是该途径中最常见的受影响的成员之一。在本研究中，我们检查了p16表达在局部晚期前列腺癌患者中的预后价值，这些患者参加了放射治疗肿瘤组方案9202。RTOG 9202是一项比较长期（LT）和短期（ST）雄激素剥夺治疗（AD）的III期随机研究。在1514例符合条件的病例中，612例患者有足够的肿瘤材料进行p16分析。免疫组化（IHC）检测p16的表达水平。采用图像分析系统对免疫组化染色进行定量评分。结果在多因素分析中，当STAD和LTAD治疗组同时考虑时，完整的p16表达与远处转移率的降低显著相关（P = 0.032）。对于完整（高水平免疫染色）p16（平均p16指数> 81.3%）的患者，与STAD加RT相比，LTAD加放疗（RT）显著提高了前列腺癌生存率（PCS） （P = 0.0008），与STAD加RT相比，降低了远处转移的频率（P = 0.0069）。相比之下，对于p16缺失的肿瘤患者（低水平免疫染色，平均p16指数> 81.3%）。LTAD加RT显著改善生化无证据表明疾病生存优于STAD (P < 0.0001)，主要是通过降低局部进展的频率（P = 0.02），而不是远处转移，这是高p16队列的情况。结论：在所有研究患者中，低水平的p16似乎与远处转移的风险显著增加有关。p16表达水平似乎也能识别局部晚期前列腺癌患者，这些患者在LTAD后具有不同的失败模式。
Purpose Deregulation of the retinoblastoma ( RB) pathway is commonly found in virtually all known human tumors. p16, the upstream regulator of RB, is among the most commonly affected member of this pathway. In the present study, we examined the prognostic value of p16 expression in men with locally advanced prostate cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202.Patients and Methods RTOG 9202 was a phase III randomized study comparing long-term ( LT) versus short-term ( ST) androgen-deprivation therapy ( AD). Of the 1,514 eligible cases, 612 patients had adequate tumor material for p16 analysis. Expression levels of p16 were determined by immunohistochemistry ( IHC). IHC staining was scored quantitatively using an image analysis system.Results On multivariate analysis, intact p16 expression was significantly associated with decreased rate of distant metastases ( P = .0332) when both STAD and LTAD treatment arms were considered together. For patients with intact ( high levels of immunostaining) p16 ( mean p16 index > 81.3%), LTAD plus radiotherapy ( RT) significantly improved prostate cancer survival ( PCS) compared with STAD plus RT ( P = .0008) and reduced the frequency of distant metastasis ( P = .0069) compared with STAD plus RT. In contrast, for patients with tumors demonstrating p16 loss ( low levels of immunostaining, mean p16 index > 81.3%), LTAD plus RT significantly improved biochemical no evidence of disease survival over STAD ( P < .0001) primarily by decreasing the frequency of local progression ( P = .02), as opposed to distant metastasis, which was the case in the high-p16 cohort.Conclusion Low levels of p16 on image analysis appear to be associated with a significantly higher risk of distant metastases among all study patients. p16 expression levels also appear to identify patients with locally advanced prostate cancer with distinct patterns of failure after LTAD.