Department of Pathology, Yale University School of Medicine, New Haven, CT, 06510, USA.
Department of Pathology, Yale University School of Medicine, New Haven, CT, 06510, USA.
Hum Pathol. 2021 Sep;115:104-111. doi: 10.1016/j.humpath.2021.06.006. Epub 2021 Jul 1.
Insulinoma-associated protein 1 (INSM1) has been reported as a highly sensitive and specific marker of neuroendocrine tumors. INSM1 expression has also been reported, although uncommonly, in non-neuroendocrine tumors. This study aimed to elucidate potential nonspecific INSM1 expression in non-small cell non-neuroendocrine lung cancers (NSCNELCs), especially in squamous cell carcinomas (SqCCs) with basaloid features to avoid diagnostic pitfalls. Tissue microarrays (TMAs) were constructed for 324 NSCNELCs, including 196 adenocarcinomas (AdCs), 86 SqCCs, and 42 other NSCNELCs. In addition, 38 whole-tissue sections of SqCCs with basaloid features were examined. INSM1 immunostain was semiquantitively evaluated based on the percentage of nuclear staining in tumor cells, categorized as negative, focal (<10% tumor cells), and positive (>10% tumor cells). Among 324 TMAs, 6.2% (20/324) were positive for INSM1, 4.9% (16/324) were focal, and 88.9% (289/34) were negative. Of 196 AdCs, 5.1% (10/196) were positive for INSM1, 4.7% (9/196) were focal, and 90.3% (177/196) were negative. Of 86 SqCCs, 9.3% (8/86) were positive for INSM1, 5.8% (5/86) were focal, and 84.9% (73/86) were negative. Of the remaining 42 NSCNELCs, 4.8% (2/42) were positive for INSM1, 4.8% (2/42) were focal, and 90.4% (38/44) were negative. Among 38 cases of whole-tissue sections of SqCCs with basaloid features, 15.8% (6/38) were positive for INSM1, 18.4% (7/38) were focal, and 65.8% (25/38) were negative. Our study demonstrates that INSM1 is expressed in a significant subset of NSCNELCs, suggesting caution in interpreting INSM1 staining, especially with limited samples. INSM1 should not be used as a stand-alone neuroendocrine marker in differentiating primary lung tumors.
胰岛素瘤相关蛋白 1（INSM1）已被报道为神经内分泌肿瘤的高度敏感和特异性标志物。尽管不常见，但 INSM1 的表达也已在非神经内分泌肿瘤中报道。本研究旨在阐明非小细胞非神经内分泌肺癌（NSCNELC）中潜在的非特异性 INSM1 表达，特别是在具有基底样特征的鳞状细胞癌（SqCC）中，以避免诊断陷阱。为 324 例 NSCNELC 构建了组织微阵列（TMA），包括 196 例腺癌（AdC）、86 例 SqCC 和 42 例其他 NSCNELC。此外，还检查了 38 例具有基底样特征的 SqCC 全组织切片。根据肿瘤细胞核染色的百分比，对 INSM1 免疫染色进行半定量评估，分为阴性、局灶性（<10%肿瘤细胞）和阳性（>10%肿瘤细胞）。在 324 个 TMA 中，6.2%（20/324）INSM1 阳性，4.9%（16/324）局灶性，88.9%（289/34）阴性。在 196 例 AdC 中，5.1%（10/196）INSM1 阳性，4.7%（9/196）局灶性，90.3%（177/196）阴性。在 86 例 SqCC 中，9.3%（8/86）INSM1 阳性，5.8%（5/86）局灶性，84.9%（73/86）阴性。在其余 42 例 NSCNELC 中，4.8%（2/42）INSM1 阳性，4.8%（2/42）局灶性，90.4%（38/44）阴性。在 38 例具有基底样特征的 SqCC 全组织切片中，15.8%（6/38）INSM1 阳性，18.4%（7/38）局灶性，65.8%（25/38）阴性。我们的研究表明，INSM1 在显著一部分 NSCNELC 中表达，提示在解释 INSM1 染色时要谨慎，特别是在样本有限的情况下。INSM1 不应作为鉴别原发性肺肿瘤的独立神经内分泌标志物。
