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

Omar Kujan, Gary Huang, Ashwati Ravindran, Monisha Vijayan, Camile Farah

Research output: Contribution to journalArticle

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
55 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 to 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.
Original languageEnglish
JournalJournal of Oral Pathology & Medicine
DOIs
Publication statusE-pub ahead of print - 7 Jun 2019

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Oral Leukoplakia
Mouth Neoplasms
Cyclin D1
Cell Biology
Squamous Cell Carcinoma
Immunohistochemistry
Biopsy
Proteins
Epithelium

Cite this

@article{78d0329ddab941239cec27144e28a8a6,
title = "CDK4, CDK6, Cyclin D1 and Notch1 immunocytochemical expression of oral brush liquid-based cytology for the diagnosis of oral leukoplakia and oral cancer",
abstract = "ObjectivesThis 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.Methods55 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.ResultsA 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 to the cumulative protein index, CDK4/6 index, and the combined OLBC grading and CDK4/6 index.ConclusionThis 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.",
author = "Omar Kujan and Gary Huang and Ashwati Ravindran and Monisha Vijayan and Camile Farah",
year = "2019",
month = "6",
day = "7",
doi = "10.1111/jop.12902",
language = "English",
journal = "Journal of Oral Pathology & Medicine",
issn = "0904-2512",
publisher = "Wiley-Blackwell",

}

CDK4, CDK6, Cyclin D1 and Notch1 immunocytochemical expression of oral brush liquid-based cytology for the diagnosis of oral leukoplakia and oral cancer. / Kujan, Omar; Huang, Gary; Ravindran, Ashwati; Vijayan, Monisha ; Farah, Camile.

In: Journal of Oral Pathology & Medicine, 07.06.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CDK4, CDK6, Cyclin D1 and Notch1 immunocytochemical expression of oral brush liquid-based cytology for the diagnosis of oral leukoplakia and oral cancer

AU - Kujan, Omar

AU - Huang, Gary

AU - Ravindran, Ashwati

AU - Vijayan, Monisha

AU - Farah, Camile

PY - 2019/6/7

Y1 - 2019/6/7

N2 - ObjectivesThis 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.Methods55 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.ResultsA 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 to the cumulative protein index, CDK4/6 index, and the combined OLBC grading and CDK4/6 index.ConclusionThis 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.

AB - ObjectivesThis 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.Methods55 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.ResultsA 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 to the cumulative protein index, CDK4/6 index, and the combined OLBC grading and CDK4/6 index.ConclusionThis 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.

U2 - 10.1111/jop.12902

DO - 10.1111/jop.12902

M3 - Article

JO - Journal of Oral Pathology & Medicine

JF - Journal of Oral Pathology & Medicine

SN - 0904-2512

ER -