Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Histopathology. 2018 Apr;72(5):826-837. doi: 10.1111/his.13436. Epub 2018 Jan 23.
We recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX2 expression had unique clinicopathological features and a dismal prognosis. The aim of the present study was to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal squamous cell carcinomas (HPSCCs) or oropharyngeal squamous cell carcinomas (OPSCCs).
The study cohort consisted of consecutive patients with HPSCC (n = 130) and OPSCC (n = 65) who underwent surgery without preoperative therapy. On immunostaining, SOX2 was almost entirely negative in 10 of 130 HPSCCs (8%) and seven of 65 OPSCCs (11%). No significant differences were observed in clinicopathological features, including p16 status, between SOX2-positive and SOX2-negative cancers. However, patients with SOX2-negative HPSCC had significantly worse overall and recurrence-free survival than those with SOX2-positive HPSCC, whereas such a prognostic relationship was not confirmed in patients with OPSCC. In a multivariate analysis, the loss of SOX2 expression appeared to be an independent poor prognostic factor for patients with HPSCC. In a sequencing analysis, no mutation was found in SOX2. As SOX2 is known to contain an extensive CpG island before the transcription start site, methylation-specific polymerase chain reaction for the SOX2 promoter was performed. Methylated alleles were found in nine of 10 SOX2-negative HPSCCs but in none of SOX2-positive HPSCCs.
Similarly to oesophageal cancers, a small subset (8%) of HPSCCs characteristically almost completely lacking SOX2 expression appeared to be aggressive neoplasms with high recurrence rates. Promoter hypermethylation was determined to be a major mechanism underlying epigenetic SOX2 silencing.
我们最近报道，一小部分（7%）完全缺乏 SOX2 表达的食管鳞状细胞癌具有独特的临床病理特征和预后不良。本研究旨在阐明在食管癌中获得的发现是否适用于下咽鳞状细胞癌（HPSCC）或口咽鳞状细胞癌（OPSCC）。
该研究队列由连续接受手术治疗而未接受术前治疗的 HPSCC（n=130）和 OPSCC（n=65）患者组成。免疫染色显示，130 例 HPSCC 中有 10 例（8%）和 65 例 OPSCC 中有 7 例（11%）几乎完全阴性的 SOX2。SOX2 阳性和 SOX2 阴性癌症的临床病理特征，包括 p16 状态，无显著差异。然而，SOX2 阴性 HPSCC 患者的总生存和无复发生存明显低于 SOX2 阳性 HPSCC 患者，而在 OPSCC 患者中未证实这种预后关系。在多变量分析中，SOX2 表达缺失似乎是 HPSCC 患者的独立不良预后因素。在测序分析中，未发现 SOX2 突变。由于 SOX2 在转录起始位点之前含有一个广泛的 CpG 岛，因此对 SOX2 启动子进行了甲基化特异性聚合酶链反应。在 10 例 SOX2 阴性 HPSCC 中有 9 例发现了甲基化等位基因，但在 SOX2 阳性 HPSCC 中没有发现。
与食管癌类似，一小部分（8%）HPSCC 几乎完全缺乏 SOX2 表达，似乎是具有高复发率的侵袭性肿瘤。启动子超甲基化被确定为 SOX2 沉默的主要表观遗传机制。
