Immunohistochemical analyses of the expression profiles of INSM1, ATRX, DAXX and DLL3 in solid papillary carcinomas of the breast

Yanai,Hirotsugu; Ishida,Mitsuaki; Yoshikawa,Katsuhiro; Tsuta,Koji; Sekimoto,Mitsugu; Sugie,Tomoharu

doi:10.3892/ol.2022.13257

Immunohistochemical analyses of the expression profiles of INSM1, ATRX, DAXX and DLL3 in solid papillary carcinomas of the breast

Authors:
- Hirotsugu Yanai
- Mitsuaki Ishida
- Katsuhiro Yoshikawa
- Koji Tsuta
- Mitsugu Sekimoto
- Tomoharu Sugie
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Affiliations: 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
Published online on: March 1, 2022 https://doi.org/10.3892/ol.2022.13257
Article Number: 137
Copyright: © Yanai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 in situ 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.

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