Chakravarti Arnab, DeSilvio Michelle, Zhang Min, Grignon David, Rosenthal Seth, Asbell Sucha O, Hanks Gerald, Sandler Howard M, Khor Li-Yan, Pollack Alan, Shipley William
Massachusetts General Hospital/Harvard Medical School, Department of Radiation Oncology, Boston, MA 02114, USA.
J Clin Oncol. 2007 Jul 20;25(21):3082-9. doi: 10.1200/JCO.2006.08.4152.
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.
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.
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 < or = 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.
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.
视网膜母细胞瘤（RB）通路失调在几乎所有已知人类肿瘤中普遍存在。p16作为RB的上游调节因子，是该通路中最常受影响的成员之一。在本研究中，我们检测了参与放射治疗肿瘤学组9202方案的局部晚期前列腺癌男性患者中p16表达的预后价值。
RTOG 9202是一项III期随机研究，比较长期（LT）与短期（ST）雄激素剥夺治疗（AD）。在1514例符合条件的病例中，612例患者有足够的肿瘤材料用于p16分析。通过免疫组织化学（IHC）测定p16的表达水平。使用图像分析系统对IHC染色进行定量评分。
多因素分析显示，当同时考虑STAD和LTAD治疗组时，完整的p16表达与远处转移率降低显著相关（P = 0.0332）。对于p16完整（免疫染色水平高）的患者（平均p16指数> 81.3%），与STAD加放疗（RT）相比，LTAD加放疗显著提高了前列腺癌生存率（PCS）（P = 0.0008），并降低了远处转移频率（P = 0.0069）。相比之下，对于显示p16缺失（免疫染色水平低，平均p16指数≤81.3%）的肿瘤患者，LTAD加放疗主要通过降低局部进展频率（P = 0.02），而非远处转移频率（高p16队列中的情况），显著提高了无疾病生化生存（P < 0.0
