Nuclear F-actin Cytology in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.

Modulation of RTK by sEcad: a putative mechanism for oncogenicity in oropharyngeal SCCs.

OBJECTIVE: Heightened levels of sEcad are found in the serum of patients with cancer and correlate with an unfavorable prognosis and later-stages of disease. In this study, we explored whether sEcad is elevated in human OPSCC specimens and FaDu cells. Additionally, we investigated sEcad-EGFR and sEcad-IGF-1R interactions and performed a functional analysis of sEcad in OPSCC cancers. MATERIALS AND METHODS: sEcad, EGFR, and IGF-1R levels were examined in human OPSCC specimens and cells by immunoblotting. sEcad-EGFR and sEcad-IGF-1R interactions were examined by immunoprecipitation and immunoblot assays. Levels of sEcad on EGFR and IGF-1R pathway components were evaluated by IB. The effects of sEcad on OPSCC proliferation, migration, and invasion were assessed using standard cellular assays. RESULTS: Statistical analysis demonstrated that sEcad levels were significantly higher in OPSCC primary tumors and cells compared with normal controls. IP studies indicated that sEcad associated with EGFR and IGF-1R, and addition of sEcad resulted in a statistically significant increase in downstream signaling. Finally, cell-based assays demonstrated enhanced sEcad-induced proliferation, migration, and invasion, which was blocked by EGFR and IGF-1R inhibitors. CONCLUSIONS: These findings suggest that sEcad may play an important role in OPSCC oncogenicity via its interaction and activation of EGFR and IGF-1R.