J Korean Assoc Oral Maxillofac Surg 2018; 44(4): 182~190
Role of E-cadherin and cyclin D1 as predictive markers of aggression and clonal expansion in head and neck squamous cell carcinoma
Khushdeep Shergill1, Arijit Sen1, Hari Janardanan Pillai2
Departments of 1Pathology and 2General Surgery, Armed Forces Medical College, Pune, India
Khushdeep Shergill
Department of Pathology, Armed Forces Medical College, Pune 411040, India
TEL: +91-07030399112 FAX: +91-2026363300 E-mail: shergillkhushdeep@gmail.com
ORCID: https://orcid.org/0000-0001-7830-9700
Received October 1, 2017; Revised December 6, 2017; Accepted December 27, 2017.; Published online August 31, 2018.
© Korean Association of Oral and Maxillofacial Surgeons. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objectives: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Inconsistency in various histopathologic features for predicting nodal metastasis and overall prognosis and a better understanding of molecular mechanisms of tumourigenesis have shifted the focus to a search for more definitive predictive markers. To identify the role of two immunohistochemical (IHC) markers, E-cadherin and cyclin D1, as predictive markers of aggressiveness in HNSCC and to assess clonal expansion of tumour cells.
Materials and Methods: A total of 66 cases of HNSCC with neck node dissection were studied. IHC was performed on primary tumour sections and lymph nodes showing metastatic deposits. Histopathological parameters such as tumour grade and TNM stage together with nodal status were compared according to expression of the two markers. Fischer’s chi-square test was used to assess the correlation between the two markers and histopathological parameters.
Results: Out of 66 cases studied, 37 showed LN metastasis. Most of the patients were male, and the most common tumour site was buccal mucosa. We found a significant association between loss of E-cadherin and node metastasis (P<0.001) and higher TNM stage (P<0.001). Cyclin D1 overexpression was significantly associated with only nodal metastasis (P=0.007). No significant association with tumour grade was found for either marker. The subgroup of E-cadherin loss with cyclin D1 overexpression was associated with the maximum incidence of nodal metastasis and higher TNM stage, highlighting the importance of using a combination of these two markers. A significant association was noted between the expression of markers at the primary site and at nodal deposits, indicating clonal expansion.
Conclusion: A combination of the two markers E-cadherin and cyclin D1 can predict prognosis in HNSCC, although tumour heterogeneity may affect this association in some cases.
Keywords: Head and neck cancer, E-cadherin, Cyclin D1, Metastasis, Predictive markers
Fig. 1. Scoring of cyclin D1 nuclear staining in head and neck squamous cell carcinoma. A. ×40 (score, 0). B. ×10 (score, 2+). C. ×10 (score, 3+). D. ×40 (score, 3+). E. ×10 (score, 4+). F. ×40 (score, 4+).

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