CD44-SNA1 Integrated Cytopathology for Delineation of High Grade Dysplastic and Neoplastic Oral Lesions

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2023 Sep 25

PMID 37747904

Authors

Sumsum P Sunny

Ravindra D R

Aditi Hariharan

Nirza Mukhia

Shubha Gurudath

Keerthi G

Subhashini Raghavan

Trupti Kolur

Vivek Shetty

Vidya Bushan R

Avadhesha Surolia

Satyajit T

Pavithra Chandrashekhar

Nisheena R

Hardik J Pandya

Vijay Pillai

Praveen Birur N

Moni A Kuriakose

Amritha Suresh

Affiliations

Soon will be listed here.

Abstract

The high prevalence of oral potentially-malignant disorders exhibits diverse severity and risk of malignant transformation, which mandates a Point-of-Care diagnostic tool. Low patient compliance for biopsies underscores the need for minimally-invasive diagnosis. Oral cytology, an apt method, is not clinically applicable due to a lack of definitive diagnostic criteria and subjective interpretation. The primary objective of this study was to identify and evaluate the efficacy of biomarkers for cytology-based delineation of high-risk oral lesions. A comprehensive systematic review and meta-analysis of biomarkers recognized a panel of markers (n: 10) delineating dysplastic oral lesions. In this observational cross sectional study, immunohistochemical validation (n: 131) identified a four-marker panel, CD44, Cyclin D1, SNA-1, and MAA, with the best sensitivity (>75%; AUC>0.75) in delineating benign, hyperplasia, and mild-dysplasia (Low Risk Lesions; LRL) from moderate-severe dysplasia (High Grade Dysplasia: HGD) along with cancer. Independent validation by cytology (n: 133) showed that expression of SNA-1 and CD44 significantly delineate HGD and cancer with high sensitivity (>83%). Multiplex validation in another cohort (n: 138), integrated with a machine learning model incorporating clinical parameters, further improved the sensitivity and specificity (>88%). Additionally, image automation with SNA-1 profiled data set also provided a high sensitivity (sensitivity: 86%). In the present study, cytology with a two-marker panel, detecting aberrant glycosylation and a glycoprotein, provided efficient risk stratification of oral lesions. Our study indicated that use of a two-biomarker panel (CD44/SNA-1) integrated with clinical parameters or SNA-1 with automated image analysis (Sensitivity >85%) or multiplexed two-marker panel analysis (Sensitivity: >90%) provided efficient risk stratification of oral lesions, indicating the significance of biomarker-integrated cytopathology in the development of a Point-of-care assay.

Citing Articles

AI in Cytopathology: A Narrative Umbrella Review on Innovations, Challenges, and Future Directions.

Giansanti D J Clin Med. 2024; 13(22).

PMID: 39597889 PMC: 11594881. DOI: 10.3390/jcm13226745.

Holistic Approach for the Early Detection of Oral Cancer: A Comprehensive Training Module.

Gurushanth K, Sunny S, Raghavan S, Thakur H, Majumder B, Srinivasan P J Maxillofac Oral Surg. 2024; 23(4):816-823.

PMID: 39118933 PMC: 11303606. DOI: 10.1007/s12663-024-02198-1.

References

Ohyama C, Hosono M, Nitta K, Oh-Eda M, Yoshikawa K, Habuchi T . Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy. Glycobiology. 2004; 14(8):671-9. DOI: 10.1093/glycob/cwh071. View

Whiting P, Rutjes A, Westwood M, Mallett S, Deeks J, Reitsma J . QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011; 155(8):529-36. DOI: 10.7326/0003-4819-155-8-201110180-00009. View

Tripathi S, Matta A, Kaur J, Grigull J, Chauhan S, Thakar A . Overexpression of prothymosin alpha predicts poor disease outcome in head and neck cancer. PLoS One. 2011; 6(5):e19213. PMC: 3088661. DOI: 10.1371/journal.pone.0019213. View

Scott I, Odell E, Chatrath P, Morris L, Davies R, Vowler S . A minimally invasive immunocytochemical approach to early detection of oral squamous cell carcinoma and dysplasia. Br J Cancer. 2006; 94(8):1170-5. PMC: 2361243. DOI: 10.1038/sj.bjc.6603066. View

Baeten J, Johnson A, Sunny S, Suresh A, Birur P, Uma K . Chairside molecular imaging of aberrant glycosylation in subjects with suspicious oral lesions using fluorescently labeled wheat germ agglutinin. Head Neck. 2017; 40(2):292-301. DOI: 10.1002/hed.24943. View

Moharil R, Khandekar S, Dive A, Bodhade A . Cyclin D1 in oral premalignant lesions and oral squamous cell carcinoma: An immunohistochemical study. J Oral Maxillofac Pathol. 2021; 24(2):397. PMC: 7802865. DOI: 10.4103/jomfp.JOMFP_164_20. View

Messadi D . Diagnostic aids for detection of oral precancerous conditions. Int J Oral Sci. 2013; 5(2):59-65. PMC: 3707069. DOI: 10.1038/ijos.2013.24. View

Skandarajah A, Sunny S, Gurpur P, Reber C, DAmbrosio M, Raghavan N . Mobile microscopy as a screening tool for oral cancer in India: A pilot study. PLoS One. 2017; 12(11):e0188440. PMC: 5703562. DOI: 10.1371/journal.pone.0188440. View

Baeten J, Suresh A, Johnson A, Patel K, Kuriakose M, Flynn A . Molecular imaging of oral premalignant and malignant lesions using fluorescently labeled lectins. Transl Oncol. 2014; 7(2):213-20. PMC: 4101339. DOI: 10.1016/j.tranon.2014.02.006. View

10.

Chiang W, Liu S, Fang L, Lin C, Wu M, Chen Y . Overexpression of galectin-1 at the tumor invasion front is associated with poor prognosis in early-stage oral squamous cell carcinoma. Oral Oncol. 2007; 44(4):325-34. DOI: 10.1016/j.oraloncology.2007.03.004. View

11.

Idrees M, Farah C, Sloan P, Kujan O . Oral brush biopsy using liquid-based cytology is a reliable tool for oral cancer screening: A cost-utility analysis: Oral brush biopsy for oral cancer screening. Cancer Cytopathol. 2022; 130(9):740-748. PMC: 9544877. DOI: 10.1002/cncy.22599. View

12.

Moher D, Liberati A, Tetzlaff J, Altman D . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097. PMC: 2707599. DOI: 10.1371/journal.pmed.1000097. View

13.

Sankaranarayanan R, Ramadas K, Thomas G, Muwonge R, Thara S, Mathew B . Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet. 2005; 365(9475):1927-33. DOI: 10.1016/S0140-6736(05)66658-5. View

14.

Abram T, Floriano P, Christodoulides N, James R, Kerr A, Thornhill M . 'Cytology-on-a-chip' based sensors for monitoring of potentially malignant oral lesions. Oral Oncol. 2016; 60:103-11. PMC: 5056560. DOI: 10.1016/j.oraloncology.2016.07.002. View

15.

Sunny S, Khan A, Rangarajan M, Hariharan A, N P, Pandya H . Oral epithelial cell segmentation from fluorescent multichannel cytology images using deep learning. Comput Methods Programs Biomed. 2022; 227:107205. DOI: 10.1016/j.cmpb.2022.107205. View

16.

Matta A, Tripathi S, Desouza L, Grigull J, Kaur J, Chauhan S . Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma. Int J Cancer. 2009; 125(6):1398-406. DOI: 10.1002/ijc.24517. View

17.

Johnson A, Baeten J, Patel K, Killian M, Sunny S, Suresh A . Evaluation of a Lectin-Based Imaging System for the Chairside Detection of Oral Dysplasia and Malignancy. J Oral Maxillofac Surg. 2019; 77(9):1941-1951. DOI: 10.1016/j.joms.2019.03.012. View

18.

Surendran S, Siddappa G, Mohan A, Hicks Jr W, Jayaprakash V, Mimikos C . Cancer stem cell and its niche in malignant progression of oral potentially malignant disorders. Oral Oncol. 2017; 75:140-147. PMC: 5880641. DOI: 10.1016/j.oraloncology.2017.11.003. View

19.

Kaur J, Matta A, Kak I, Srivastava G, Assi J, Leong I . S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia. Int J Cancer. 2013; 134(6):1379-88. DOI: 10.1002/ijc.28473. View

20.

Sunny S, Baby A, James B, Balaji D, N V A, Rana M . A smart tele-cytology point-of-care platform for oral cancer screening. PLoS One. 2019; 14(11):e0224885. PMC: 6857853. DOI: 10.1371/journal.pone.0224885. View