Immunohistochemical evaluation of gastric‑type markers in primary extramammary Paget disease: Differential MUC5AC expression between in situ and invasive lesions

Primary extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma characterised by intraepithelial proliferation of mucin‑containing carcinoma cells, with invasive carcinoma occasionally present. A characteristic immunohistochemical feature of primary EMPD is expression of MUC5AC, a gastric‑type mucin core protein; however, the expression of MUC5AC in invasive EMPD remains controversial. Furthermore, the expression of other gastric‑type markers, including hepatocyte nuclear factor 4α (HNF4α) and claudin 18, has not been fully investigated in primary EMPD. The present study aimed to clarify the expression profiles of MUC5AC in both in situ and invasive EMPD lesions, as well as to evaluate HNF4α and claudin 18 expression in primary EMPD. Consecutive patients with primary EMPD who underwent surgical resection were included. Immunohistochemical staining for MUC5AC, HNF4α and claudin 18 was performed, and the results were semi‑quantitatively assessed using a four‑tier scoring system (0, <5%; 1, 5‑25%; 2, 26‑50%; 3, >50% positive neoplastic cells) in in situ and invasive components, when present. A total of 40 patients (9 female patients and 31 male patients) were included, comprising 25 cases in situ and 15 invasive cases. MUC5AC expression was observed in 24 in situ and 14 invasive EMPD cases. No significant difference in MUC5AC expression scores in in situ lesions was observed between in situ‑only and invasive EMPD cases (P=0.35). By contrast, MUC5AC expression scores in invasive components were significantly lower than those in the corresponding in situ lesions of invasive EMPD (P=0.0015). Neither in situ nor invasive EMPD lesions showed immunoreactivity for HNF4α or claudin 18. These findings obtained from the second‑largest cohort study to date suggested that MUC5AC expression was reduced in invasive lesions. Furthermore, MUC5AC expression in EMPD was not associated with the expression of HNF4α, despite its role in inducing MUC5AC expression in normal gastric tissues.