Department of Pathology, Fudan University Shanghai Cancer Center.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Am J Surg Pathol. 2023 Sep 1;47(9):1059-1066. doi: 10.1097/PAS.0000000000002081. Epub 2023 Jun 26.
POU2F3 (POU class 2 homeobox 3) is a novel transcription factor used to define the special molecular subtype of small cell lung cancer (SCLC) known as SCLC-P. Nevertheless, the sensitivity and specificity of POU2F3 immunohistochemical (IHC) staining have not been fully investigated. In this study, we explored the expression of POU2F3 by IHC in a large cohort of SCLC clinical samples (n=246), other common lung cancer types (n=2207), and various other cancer types (n=194). The results showed that POU2F3 was strongly nuclear stained in 13.41% (33/246) of SCLC cases, with negative or minimal labeling for thyroid transcription factor-1 and neuroendocrine (NE) markers. Compared with POU2F3-negative SCLC, SCLC-P harbored fewer TP53 and RB1 mutations. POU2F3 was also expressed in 3.13% (8/256) of squamous cell carcinomas (SCCs) and 20% (2/10) of large cell NE carcinomas (LCNECs), whereas other lung cancer types were negative. In addition to lung cancer, POU2F3 was positive in 22.2% (4/18) of thymic tumors. All other tumors were POU2F3-negative except for thymic carcinoma, although sparsely distributed weak nuclear staining was observed in lung adenocarcinoma, cervical SCC, and colorectal carcinoma. The sensitivity and specificity of POU2F3 in NE-low/negative SCLC were 82.1% and 99.4%, respectively. Notably, some rare unique patterns of POU2F3 expression were observed. One case of thymic SCC was characterized by diffuse and uniform cytomembrane staining. One case of esophageal NE tumor was nuclear-positive, while the normal proliferating squamous epithelium was strongly membrane-stained. This is the largest cohort of clinical samples to confirm that POU2F3 is a highly sensitive and specific diagnostic marker for NE-low/negative SCLC.
POU2F3（POU 类 2 同源盒 3）是一种新型转录因子，用于定义小细胞肺癌（SCLC）的特殊分子亚型，即 SCLC-P。然而，POU2F3 免疫组织化学（IHC）染色的敏感性和特异性尚未得到充分研究。在这项研究中，我们通过 IHC 对 246 例 SCLC 临床样本、2207 例其他常见肺癌类型和 194 例其他各种癌症类型的 POU2F3 表达进行了探索。结果显示，在 13.41%（33/246）的 SCLC 病例中，POU2F3 呈强烈核染色，甲状腺转录因子-1 和神经内分泌（NE）标志物呈阴性或最小标记。与 POU2F3 阴性的 SCLC 相比，SCLC-P 携带较少的 TP53 和 RB1 突变。POU2F3 也在 3.13%（8/256）的鳞状细胞癌（SCC）和 20%（2/10）的大细胞 NE 癌（LCNEC）中表达，而其他肺癌类型则为阴性。除了肺癌，POU2F3 在 22.2%（4/18）的胸腺瘤中为阳性。除了胸腺癌外，所有其他肿瘤均为 POU2F3 阴性，尽管在肺腺癌、宫颈 SCC 和结直肠腺癌中观察到稀疏分布的弱核染色。POU2F3 在 NE 低/阴性 SCLC 中的敏感性和特异性分别为 82.1%和 99.4%。值得注意的是，观察到一些罕见的 POU2F3 表达独特模式。1 例胸腺癌表现为弥漫均匀的细胞浆染色。1 例食管神经内分泌肿瘤为核阳性，而正常增殖的鳞状上皮强烈膜染色。这是最大的临床样本队列，证实 POU2F3 是一种高度敏感和特异的 NE 低/阴性 SCLC 诊断标志物。
