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

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.

The Clinical Impact of Death Domain-Associated Protein and Holliday Junction Recognition Protein Expression in Cancer: Unmasking the Driving Forces of Neoplasia

“…Low levels of DAXX expression associated with lower DFS but not OS [27]. In solid papillary carcinoma (SPC) patients, loss of DAXX expression was significantly associated with lymphatic invasion [28].…”

“…39 solid papillary carcinoma (SPC) specimens (18 SPC in situ and 21 SPC invasive) -IHC Loss of DAXX expression was significantly associated with lymphatic invasion [28] HJURP 44 in situ breast carcinoma specimens -IHC…”

ATRX is a predictive marker for endocrinotherapy and chemotherapy resistance in HER2-/HR+ breast cancer through the regulation of the AR, GLI3 and GATA2 transcriptional network

“…Additionally, survival analysis on cervical carcinoma suggested that the loss-offunction of ATRX was associated with a better prognosis in patients treated with chemo-radiation [12]. However, to date, the potential role of ATRX in BC, especially its role in the HER2-/HR+ subtype, remains inadequately explored [15]. Dysregulated transcription factors (TF) mediate aberrant gene expression, which is the hallmark properties of drug resistance in tumours [16].…”