Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
J Clin Pathol. 2012 Mar;65(3):248-53. doi: 10.1136/jclinpath-2011-200413. Epub 2011 Nov 12.
Deregulated chromatin remodelling often leads to aberrant gene expression in cells, thereby implicating tumour development and progression. As a subunit of remodelling and spacing factor complex, Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness in common carcinomas. However, the expression of Rsf-1 has never been reported in nasopharyngeal carcinoma (NPC). This study aimed at evaluating the expression status, associations with clincopathological variables and prognostic implications of Rsf-1 in a well-defined cohort of NPC.
Rsf-1 immunoexpression was retrospectively assessed in biopsies of 108 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The results were correlated with the clinicopathological features, therapeutic response, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-specific survival (DSS).
Present in 49 cases (45%), Rsf-1 overexpression was associated with N(2,3) status (p=0.016), American Joint Committee on Cancer stage 3, 4 (p=0.004), and incomplete therapeutic response (p=0.041). In multivariate analyses, Rsf-1 overexpression not only emerged as the sole independent adverse prognosticator for LRFS (p=0.0002, RR 5.287) but also independently predicted worse DMFS (p=0.0011, RR 3.185) and DSS (p<0.0001, RR 4.442), along with T(3,4) (p=0.0454) and N(2,3) (p=0.0319), respectively.
Rsf-1 overexpression is common and is associated with adverse prognosticators and therapeutic response, which confers tumour aggressiveness through chromatin remodelling, and represents a potential prognostic biomarker in NPC.
染色质重塑失调通常会导致细胞中异常基因表达,从而牵连肿瘤的发生和发展。作为重塑和间隔因子复合物的一个亚基,Rsf-1(HBXAP)是一种具有组蛋白伴侣功能的新型核蛋白,介导 ATP 依赖的染色质重塑,并赋予常见癌种的肿瘤侵袭性。然而,Rsf-1 在鼻咽癌(NPC)中的表达从未被报道过。本研究旨在评估 Rsf-1 在一个明确的 NPC 患者队列中的表达状态、与临床病理变量的相关性及其对预后的影响。
回顾性评估 108 例连续 NPC 患者活检标本中 Rsf-1 的免疫表达,这些患者无初始远处转移,并接受了一致的治疗指南。结果与临床病理特征、治疗反应、局部无复发生存(LRFS)、无远处转移生存(DMFS)和疾病特异性生存(DSS)相关联。
在 49 例(45%)患者中存在 Rsf-1 过表达,其与 N(2,3)状态相关(p=0.016)、美国癌症联合委员会分期 3、4 期(p=0.004)和不完全治疗反应(p=0.041)相关。在多变量分析中,Rsf-1 过表达不仅是 LRFS 的唯一独立不良预后因素(p=0.0002,RR 5.287),还独立预测了更差的 DMFS(p=0.0011,RR 3.185)和 DSS(p<0.0001,RR 4.442),以及 T(3,4)(p=0.0454)和 N(2,3)(p=0.0319)。
Rsf-1 过表达很常见,与不良预后因素和治疗反应相关,通过染色质重塑赋予肿瘤侵袭性,代表 NPC 中的一个潜在预后生物标志物。