Immunohistochemical expression levels of cyclin D1 and CREPT reflect the course and prognosis in oral precancerous lesions and squamous cell carcinoma.

Cyclin D1 is the most essential progressive regulator of the cell cycle, and its transcription is enhanced by CREPT (cell cycle-related and expression-elevated protein in tumour). These molecules regulate cell growth, and their aberrant expression can cause malignant transformation. In this study, the expression of these molecules was explored to investigate the molecular alterations in oral precancerous lesions and squamous cell carcinoma. Cyclin D1 and CREPT expression was examined immunohistochemically in tissue specimens from 55 patients with oral epithelial precursor lesions (OEPLs) and 84 patients with oral squamous cell carcinoma (OSCC). Associations between the results and clinicopathological variables were examined. Cyclin D1 and CREPT expression levels were higher in OSCC than in OEPLs. Furthermore, there were statistically significant differences in cyclin D1 expression among the different grades of OEPLs and OSCC lesions. In OSCC, there were statistically significant differences in CREPT expression according to sex, T stage, and degree of differentiation. In addition, the expression of both molecules was significantly correlated with postoperative metastasis and modes of invasion. The expression of cyclin D1 and CREPT was found to depend upon the state of development and progression of the oral epithelial lesions, and clinicopathological behaviours might be affected by these molecules in OSCC.

Regulatory T cells and M2-polarized tumour-associated macrophages are associated with the oncogenesis and progression of oral squamous cell carcinoma.

Regulatory T cells (Tregs) and tumour-associated macrophages (TAMs) contribute to the tumour microenvironment by inhibiting anti-tumour immune responses. This study was performed to investigate the roles of Tregs and TAMs in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPL). The expression of Treg markers CD25 and FoxP3 and TAM markers CD163 and CD204 was investigated in 82 OSCC and 45 OEPL specimens, and their associations with clinicopathological parameters were analyzed. Correlations were found among CD25, FoxP3, CD163, and CD204 levels (P < 0.001), and these targets were up-regulated in OSCC compared to OEPL (P < 0.001). In OSCC, infiltration of Tregs and/or M2 TAMs was associated with sex and clinicopathological features, such as tumour size, nodal metastasis, tissue differentiation, stromal reaction, invasive behaviour, and invasive depth. In OEPL, CD25, FoxP3, CD163, and CD204 immunoreactivities were significantly associated with sex, postoperative recurrence, and cancerization to OSCC. This study is novel in showing that the infiltration of Tregs and M2 TAMs is significantly associated with the progression of premalignant lesions to OSCC. This suggests that these cells represent prognostic biomarkers for premalignant lesion progression and that immunotherapeutic approaches to control Treg/M2 TAM numbers could protect against progression to malignancy.