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EXPRESSION OF KI-67, CORNULIN AND ISG15 IN NON-INVOLVED MUCOSAL SURGICAL
MARGINS AS PREDICTIVE MARKERS FOR RELAPSE IN ORAL SQUAMOUS CELL CARCINOMA
(OSCC)
NMRR-19-630-47477

Lew HL, Kallarakkal TG

Introduction: Relapse in OSCC is often observed in histologically non-involved surgical
margins. This indicates the possible presence of field alteration in the non-involved surgical
margins, which in turn leads to local recurrence or second primary tumour. The
identification of specific biomarkers that could predict relapse of OSCC would help the
clinicians in treatment planning for patients. Objectives: The objectives of this study were
to evaluate the expression of Ki-67, Cornulin and ISG15 in the non-involved surgical margins
and its association with clinicopathological prognosticators and relapse of OSCC. Materials
and Methods: Immunohistochemistry was used in staining of non-involved mucosal
surgical margins from study (relapse) group (n = 23), control (non-relapse) group (n = 32)
and normal oral mucosa (n = 5) with Ki-67, Cornulin and ISG15. Association between the
expression of markers with clinicopathological prognosticators and relapse in OSCC was
analysed statistically using Chi-square tests. Binary logistic regression analysis was used to
determine predictors of relapse in OSCC. Results: In the study group, significant low
expression of Cornulin (P = 0.032) and ISG15 (P = 0.047) was observed. Low expression of
Cornulin was also significantly associated with relapse (P = 0.004) of OSCC and primary
tumours involving non-tongue sites (P = 0.013). Surgical margins exhibiting high expression
of Ki-67 was significantly reduced in female patients (P = 0.041). Clinicopathological
prognosticators such as age above 57.5 years (P < 0.001), Chinese ethnicity (P = 0.009),
Indian ethnicity (P = 0.007), alcohol use (P = 0.025), epithelial dysplasia in surgical margins
(P = 0.045) and type III and IV pattern of invasion of tumour (P = 0.007) were significantly
associated with relapse of OSCC. Binary logistic regression analysis showed decreased
expression of Cornulin (P = 0.018) and increased patient’s age (P = 0.008) were predictors
of relapse in OSCC, with 34-fold risk and 18-fold risk, respectively. Conclusions: Relapse of
OSCC could be predicted by decreased expression of Cornulin in the non-involved surgical
margins. Validation of the role of Ki-67 and ISG15 in predicting relapse of OSCC would
require larger cohorts. Taken together, Cornulin as a predictor in the relapse of OSCC was
suggested.

Oral presentation at the 12 Postgraduate Conference, Faculty of Dentistry, University of Malaya on 18 September 2019.
th
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Dr Lew Huai Lin Assoc. Prof. Dr Thomas George Kallarakkal
Department of Oral Pathology & Oral Medicine Department of Oral & Maxillofacial Clinical Sciences
Queen Elizabeth Hospital Faculty of Dentistry
Kota Kinabalu Sabah University of Malaya

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