CDK4, CDK6, cyclin D1 and Notch1 immunocytochemical expression of oral brush liquid‐based cytology for the diagnosis of oral leukoplakia and oral cancer

Abstract

Objectives This study aimed to investigate the feasibility of using oral liquid‐based brush cytology (OLBC) coupled with immunocytochemistry as a minimally invasive approach to stratify the cancer risk in patients with oral leukoplakia. Methods Fifty‐five patients diagnosed with either oral leukoplakia (OLK) or oral squamous cell carcinoma (OSCC) were recruited. All patients underwent oral brush biopsy followed by surgical biopsy. 275 liquid‐based cytology preparations were made. Pap‐stained OLBC slides were assessed using the modified 2014 Bethesda Cytology system. The expression of CDK4, CDK6, cyclin D1, and Notch 1 was immunocytochemically analysed and compared against the histopathological diagnosis. A combined index score of OLBC grading and protein expression was calculated. Results A significant association was found between the definitive histopathological diagnosis and the cytological interpretation (P = 0.0005). The index scores of CDK4, CDK6, and cyclin D1 were significantly associated with the development of disease from non‐dysplastic epithelium to OSCC. No significant association was observed between the Notch 1 index score and disease stage. The diagnostic accuracy of OLBC showed the highest values of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy: 84.6%, 70.4%, 73.3%, 82.6%, and 78.8%, respectively, compared with the cumulative protein index, CDK4/6 index, and the combined OLBC grading and CDK4/6 index. Conclusion This study has also demonstrated the efficacy of the use of OLBC in the detection of OED and OSCC, and showed that the use of CDK4, CDK6, cyclin D1, and Notch 1 immunocytochemistry failed to improve the diagnostic accuracy of OLBC suggesting they are not useful in the early detection of OSCC.

Efficacy of oral brush cytology cell block immunocytochemistry in the diagnosis of oral leukoplakia and oral squamous cell carcinoma

“…All patients underwent oral brush biopsy using Orcellex ® brush (Rovers Medical Devices, the Netherlands) under local anaesthesia before surgical biopsies as described by Kujan et al 16 All OLBC samples were preserved in methanol-based preservative vials (ThinPrep ® PreservCyt, Hologic Inc., MA, USA) and transported to the laboratory to prepare liquid-based cytology slides using the ThinPrep ® 2000 processor (Hologic Inc.) according to the manufacturer's instructions. Surgical biopsies were performed on all lesions, and histopathological diagnosis was considered as the standard point of reference for definitive diagnosis.…”

“…Samples were selected from those accumulated by us for other projects evaluating the utility of OLBC in the diagnosis of oral mucosal lesions. 8,16 Cases were included if the subject was aged more than 18 years and provided informed consent. Subjects were diagnosed clinically with either OLK or OSCC.…”

<p><em>PTHLH</em> Predicts the Prognosis of Patients with Oral Leukoplakia</p>

“…For example, CCND1, EZH2, Ki67, IL-6, Snail, and Axin2 have been found to be upregulated in oral leukoplakia. 4,8,[21][22][23][24] Furthermore, a copy number variation frequently occurs at 3p, 9p, and 13q loci during progressive dysplasia of oral leukoplakia, 25 as oral leukoplakia represents an uncontrollable inflammatory lesion. To some extent, molecular mechanism research can reveal the uncontrolled inflammation mechanism of OSCC.…”

“…are considered highrisk factors for oral leukoplakia. [4][5][6][7] As a result, nonspecific treatments are used to cure the disease.…”

<p>Mutational Characterization and Potential Prognostic Biomarkers of Chinese Patients with Esophageal Squamous Cell Carcinoma</p>

“…11 As both an oncogene and a tumor suppressor, NOTCH1 is closely related to human carcinogenesis, and NOTCH1 mutations have been observed in many cancers. [12][13][14][15] NOTCH signaling may inhibit tumorigenesis in ESCC. 16 Curcumin can affect the interaction between NOTCH signal and other signals, which is of great significance in chemoprevention and clinical treatment of ESCC.…”