Yanai Hirotsugu, Ishida Mitsuaki, Yoshikawa Katsuhiro, Tsuta Koji, Sekimoto Mitsugu, Sugie Tomoharu
Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1191, Japan.
Department of Pathology and Division of Diagnostic Pathology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan.
Oncol Lett. 2022 Apr;23(4):137. doi: 10.3892/ol.2022.13257. Epub 2022 Mar 1.
Solid papillary carcinoma (SPC) is a rare but distinct clinicopathological feature of breast cancer characterised by frequent neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a useful neuroendocrine marker for various neuroendocrine tumours. α-thalassemia/mental retardation syndrome X-linked protein (ATRX) and death domain-associated protein (DAXX) are useful prognostic markers for patients with pancreatic neuroendocrine tumours. However, to the best of our knowledge, few studies have addressed INSM1 expression in SPCs. Although ATRX, DAXX and δ-like canonical notch ligand 3 (DLL3) are frequently expressed in neuroendocrine lung carcinomas, there are no reports on their expression in SPCs. Therefore, the present study aimed to analyse the expression profiles of INSM1, ATRX, DAXX and DLL3 in the largest series of patients with SPC that has been, to the best of our knowledge, studied until now. Immunohistochemical analyses were performed to determine chromogranin A, synaptophysin, INSM1, ATRX, DAXX and DLL3 expression in 39 specimens surgically resected from patients with SPC (18 SPC and 21 SPC invasive). The associations between the expression of these markers and the clinicopathological factors were investigated. Chromogranin A, synaptophysin and INSM1 were expressed in 64.1, 100 and 92.3% of the patients, respectively. Both ATRX and DAXX expression was observed in 28.2% of the patients. No patient expressed DLL3. Lack of INSM1 or chromogranin A expression was significantly associated with advanced pathological stages in patients with SPC (P=0.033) and in patients with invasive SPC (P=0.012), showing a tendency for a high Ki-67 labelling index (LI) and advanced histological grade in patients with invasive SPC. Loss of ATRX or DAXX expression was significantly associated with lymphatic invasion, but not with histological grade, Ki-67 LI or presence of invasive tumours. Thus, INSM1 was demonstrated to be a useful diagnostic marker for SPCs. Overall, detecting the lack of INSM1 or chromogranin A expression may be useful for analysing the characteristics of tumour cells in SPCs.
实性乳头状癌（SPC）是一种罕见但具有独特临床病理特征的乳腺癌，其特点是频繁出现神经内分泌分化。胰岛素瘤相关蛋白1（INSM1）是一种用于各种神经内分泌肿瘤的有用神经内分泌标志物。α-地中海贫血/智力发育迟缓综合征X连锁蛋白（ATRX）和死亡结构域相关蛋白（DAXX）是胰腺神经内分泌肿瘤患者的有用预后标志物。然而，据我们所知，很少有研究探讨INSM1在SPC中的表达。尽管ATRX、DAXX和δ样经典Notch配体3（DLL3）在神经内分泌肺癌中经常表达，但尚无关于它们在SPC中表达的报道。因此，本研究旨在分析在我们所知的迄今为止研究的最大系列SPC患者中INSM1、ATRX、DAXX和DLL3的表达谱。对39例SPC患者（18例SPC和21例浸润性SPC）手术切除标本进行免疫组织化学分析，以确定嗜铬粒蛋白A、突触素、INSM1、ATRX、DAXX和DLL3表达情况。研究这些标志物表达与临床病理因素之间的关联。嗜铬粒蛋白A、突触素和INSM1分别在64.1%、100%和92.3%的患者中表达。28.2%的患者同时观察到ATRX和DAXX表达。无患者表达DLL3。SPC患者（P=0.033）和浸润性SPC患者（P=0.012）中，INSM1或嗜铬粒蛋白A表达缺失与晚期病理分期显著相关，浸润性SPC患者显示出高Ki-67标记指数（LI）和高级别组织学分级的趋势。ATRX或DAXX表达缺失与淋巴浸润显著相关，但与组织学分级、Ki-67 LI或浸润性肿瘤的存在无关。因此，INSM1被证明是SPC的一种有用诊断标志物。总体而言，检测INSM1或嗜铬粒蛋白A表达缺失可能有助于分析SPC中肿瘤细胞的特征。
