Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Am J Surg Pathol. 2012 Aug;36(8):1158-64. doi: 10.1097/PAS.0b013e3182600eaa.
ProExC expression has been shown to perform similarly to p16 as an aid in the diagnosis of cervical dysplasia but has not been well characterized in head and neck squamous cell carcinomas (SCC). The purpose of this study is to determine whether ProExC performs similarly to p16 as a prognostic marker in oropharyngeal SCC and to evaluate the threshold of ProExC and p16 staining that correlates with survival. ProExC, p16, and human papillomavirus DNA in situ hybridization were performed on tissue microarray (TMA) cores and whole sections from 62 patients with oropharyngeal SCC. Sensitivity and specificity for high-risk HPV and correlation with overall survival (OS), cancer-specific survival (CSS), and time to distant metastasis (TDM) were calculated for ProExC and p16 at different thresholds. ProExC did not prove to be a robust marker. It showed strong correlation with OS at a 66% threshold on TMA cores, but correlation with OS was lost on whole sections. It also exhibited low sensitivity (53.7%) on TMA cores and low specificity on whole sections (65%). ProExC at a 33% threshold exhibited unacceptably low specificity and did not correlate with OS, CSS, or TDM. Sensitivity and specificity of p16 varied predictably with threshold: higher sensitivity and lower specificity with lower thresholds and vice versa for higher thresholds. p16 at a 50% threshold offers a balance between sensitivity and specificity, and correlates with OS, CSS, and TDM on whole sections; correlation with TDM is lost on TMA cores. These findings indicate that ProExC does not perform well enough to be used as a prognostic marker in oropharyngeal SCC. p16 should be used and scored as positive when at least half the tumor is strongly stained.
ProExC 的表达被证明与 p16 相似，可作为辅助诊断宫颈发育不良的指标，但在头颈部鳞状细胞癌（SCC）中尚未得到很好的描述。本研究旨在确定 ProExC 是否与 p16 一样，作为口咽 SCC 的预后标志物，并评估与生存相关的 ProExC 和 p16 染色阈值。对 62 例口咽 SCC 患者的组织微阵列（TMA）芯和全切片进行 ProExC、p16 和人乳头瘤病毒 DNA 原位杂交。计算了不同阈值下 ProExC 和 p16 对高危 HPV 的敏感性和特异性，以及与总生存期（OS）、癌症特异性生存期（CSS）和远处转移时间（TDM）的相关性。ProExC 并未证明是一种可靠的标志物。在 TMA 芯上，当阈值为 66%时，它与 OS 有很强的相关性，但在全切片上相关性丢失。在 TMA 芯上，它的敏感性（53.7%）也较低，而在全切片上的特异性（65%）较低。在 33%的阈值下，ProExC 的特异性不可接受地低，与 OS、CSS 或 TDM 均无相关性。p16 的敏感性和特异性随阈值而变化：阈值越低，敏感性越高，特异性越低，反之亦然。p16 的 50%阈值在敏感性和特异性之间取得了平衡，并且在全切片上与 OS、CSS 和 TDM 相关；在 TMA 芯上与 TDM 相关丢失。这些发现表明，ProExC 的性能不足以作为口咽 SCC 的预后标志物。当至少一半的肿瘤强烈染色时，应使用 p16 并将其评为阳性。
