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. 2021 Dec 23;16(12):e0261575.
doi: 10.1371/journal.pone.0261575. eCollection 2021.

Expression of Ki-67, Cornulin and ISG15 in non-involved mucosal surgical margins as predictive markers for relapse in oral squamous cell carcinoma (OSCC)

Padmanabha Kumar Govindaraj  1 , Thomas George Kallarakkal  2   3 , Rosnah Mohd Zain  1   3 , Wanninayake Mudiyanselage Tilakaratne  2   4 , Huai Lin Lew  5
Affiliations

Expression of Ki-67, Cornulin and ISG15 in non-involved mucosal surgical margins as predictive markers for relapse in oral squamous cell carcinoma (OSCC)

Padmanabha Kumar Govindaraj et al. PLoS One. .

Abstract

Background: Local relapse of oral squamous cell carcinoma in non-involved mucosal surgical margins indicated possibility of field alteration in the margins, which could be predicted with certain biomarkers. The objectives were to evaluate the expression of Ki-67, Cornulin and ISG15 in non-involved mucosal surgical margins and the association of clinicopathological prognosticators with local relapse in oral squamous cell carcinoma.

Methods: Surgical margins from the study (relapse) group (n = 23), control (non-relapse) group (n = 32) and normal oral mucosa (n = 5) were immunohistochemically stained using Ki-67, Cornulin and ISG15 antibodies. Association between expression of markers and clinicopathological prognosticators with local relapse in oral squamous cell carcinoma was analyzed statistically.

Results: The study group surgical margins demonstrated significantly decreased Cornulin expression (p = 0.032). Low Cornulin expression was significantly associated with local relapse (p = 0.004) and non-tongue primary tumor (p = 0.013). Although not significantly associated with local relapse, expression of Ki-67 was significantly reduced in female patients (p = 0.041). Age above 57.5 years, Chinese & Indian ethnicity, alcohol consumption, epithelial dysplasia in surgical margins, and type III and IV patterns of invasion of tumor were also significantly related to local relapse. Regression analysis showed low expression of Cornulin (p = 0.018), and increased patient's age (p = 0.008) were predictors of local relapse in oral squamous cell carcinoma, with 34-fold risk and 18-fold risk, respectively. Expression of Ki-67 and ISG15 did not show significant association with local relapse in oral squamous cell carcinoma.

Conclusion: Low expression of Cornulin is an independent predictor of relapse in oral squamous cell carcinoma.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Illustration and protocol of random sampling.
Fig 2
Fig 2. Immunohistochemical staining of the surgical margins.
Immunostaining of surgical margins; original magnification 400x. (a) Ki-67 staining on study group sample and (b) control group sample. (c) Cornulin staining on study group sample and (d) control group sample. (e) ISG15 staining on study group sample and (f) control group sample.
See this image and copyright information in PMC

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Grants and funding

This study was supported by the University of Malaya Dental Postgraduate Research Grant (DPRG, project number DPRG/10/17) and MAHSA research grant (project number: RP138/02-18). The sponsors had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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