Hammond E, Berkey Brian A, Fu Karen K, Trotti Andy, Meredith Ruby F, Jones Christopher U, Byhardt R, Horwitz E M, Ang K Kian
LDS Hospital, Salt Lake City, UT 84143, USA.
Int J Radiat Oncol Biol Phys. 2003 Nov 1;57(3):683-92. doi: 10.1016/s0360-3016(03)00642-4.
In a previous retrospective study, p105 AD, a proliferation-associated nuclear antigen density (AD), was found to be an independent prognostic factor for patients irradiated for locally advanced head-and-neck cancer. We sought to confirm this finding by analyzing patients entered on RTOG 9003, a Phase III randomized trial of altered fractionation radiotherapy.
Paraffin blocks of pretreatment biopsies of the primary tumor of patients with Stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, or supraglottic larynx, or Stage II squamous cell carcinoma of the hypopharynx or base of tongue entered on RTOG 9003 were prospectively collected at patient entry. From these paraffin blocks, areas of tumor were selected based on histologic examinations and sectioned. Nuclear suspensions were then prepared and processed for p105 antibody and DNA staining. Flow cytometric quantification of p105 labeling indices and DNA content were then performed for correlation with local-regional control and survival.
Paraffin blocks of tumor biopsies from 457 of 1073 patients entered were available for p105 determination. There was no significant difference in pretreatment characteristics between patients who had paraffin blocks available or not available. The median (range) of p105 labeling index (LI-C), p105 labeling index of cells in S phase (p105 LI-S), and p105 AD were 56 (range: 6-99), 8.255 (range: 0.913-23), and 67 (range: 5-364), respectively. Multivariate analysis of prognostic factors showed that T stage, N stage, Karnofsky performance status, and fractionation schedule were significant for local-regional control (p < 0.0001, 0.0011, <0.0001, and 0.007, respectively) and T stage, N stage, Karnofsky performance status, and tumor grade were significant for survival (p = 0.018, 0.002, <0.0001, and 0.0058, respectively). Neither p105 LI-C nor p105 LI-S nor p105 AD nor DNA ploidy was significant for local-regional control or survival.
p105 labeling indices, antigen density, and DNA ploidy do not predict the outcome of patients irradiated for advanced squamous cell carcinomas of the head and neck.
在先前的一项回顾性研究中，发现增殖相关核抗原密度（AD）p105是局部晚期头颈癌放疗患者的独立预后因素。我们试图通过分析入组RTOG 9003（一项改变分割放疗的III期随机试验）的患者来证实这一发现。
前瞻性收集了RTOG 9003入组的口腔、口咽或声门上喉III期或IV期鳞状细胞癌患者，或下咽或舌根II期鳞状细胞癌患者原发肿瘤治疗前活检的石蜡块。从这些石蜡块中，根据组织学检查选择肿瘤区域并切片。然后制备核悬液，并用p105抗体和DNA染色进行处理。接着进行p105标记指数和DNA含量的流式细胞术定量分析，以与局部区域控制和生存情况进行相关性分析。
1073名入组患者中有457名患者的肿瘤活检石蜡块可用于p105测定。有石蜡块和没有石蜡块的患者在治疗前特征方面没有显著差异。p105标记指数（LI-C）、S期细胞的p105标记指数（p105 LI-S）和p105 AD的中位数（范围）分别为56（范围：6 - 99）、8.255（范围：0.913 - 23）和67（范围：5 - 364）。预后因素的多因素分析表明，T分期、N分期、卡诺夫斯基体能状态和分割方案对局部区域控制有显著意义（分别为p < 0.0001、0.0011、<0.0001和0.007），T分期、N分期、卡诺夫斯基体能状态和肿瘤分级对生存有显著意义（分别为p = 0.018、0.002、<0.0001和0.0058）。p105 LI-C、p105 LI-S、p105 AD或DNA倍体对局部区域控制或生存均无显著意义。
p105标记指数、抗原密度和DNA倍体不能预测晚期头颈鳞状细胞癌放疗患者的预后。
