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Presence of nuclear atypia during histological investigation is often a cause of concern for pathologists while identifying tumor and non‑tumor cells in a biopsy sample of oral mucosa. Nuclear atypia is observed in severe inflammation, ulcers and reactive changes. Therefore, additional methods, such as immunohistochemistry, may help precise diagnosis. When the atypia is suggestive of tumorous or reactive origin, the lesion is diagnosed as atypical squamous epithelium (ASE). When there is severe nuclear atypia in the mucosa, such as in disorders of nuclear polarity, large nuclei, and clear nucleolus, the lesion is diagnosed as carcinoma in situ (CIS). However, it is not easy to distinguish ASE and CIS using hematoxylin and eosin staining. The present study aimed to distinguish ASE from CIS using immunohistochemistry. A total of 32 biopsy samples of either ASE or CIS cases were selected and the level of casein kinase 1ε (CK‑1ε), differentiated embryonic chondrocyte gene 1 (DEC1), proliferating cell nuclear antigen (PCNA) and CD44, which are four protein markers which have been previously linked to cancer progression, were analyzed. CK‑1ε and CD44 expression was higher in CIS samples than in ASE samples. However, DEC1 expression was lower in CIS samples than in ASE samples. PCNA expression was not markedly different between the two groups. Additionally, it was found that DEC1‑overexpressing cells had decreased levels of CK‑1ε and CD44 compared with control cells, while CK‑1ε‑overexpressing cells had relatively unchanged levels of CD44, DEC1 and PCNA. These results suggested that DEC1 negatively regulates the expression of CK‑1ε and CD44. Thus, DEC1, CK‑1ε, and CD44 were identified as mechanistically linked and clinically relevant protein biomarkers, which could help distinguish ASE and CIS.

Differential immunohistochemical expression of DEC1, CK‑1ε, and CD44 in oral atypical squamous epithelium and carcinoma in situ