Edorium Journal of

Tumor Biology

 
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Original Article
 
Clinicopathological features and prognostic implications of loss of K5 and gain of K1, K8 and K18 in oral potentially malignant lesions and squamous cell carcinomas: An immunohistochemical analysis
Sawant Sharada1, Vaidya Milind2, Chaukar Devendra3, Gangadaran Prakash4, Singh Archana5, Rajadhyax Siddheshwar6, Kannan Sadhana7, Padmavathi A8, Kane Shubhada9, Pagare Sandeep10, Kannan Ranganathan11, D'Cruz Anil12
1MSc, Scientific Officer, Vaidya Lab., Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
2PhD, Scientific Officer, Vaidya Lab., Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
3MS, Professor and Surgeon, Oral Surgery, Head and Neck Unit, Tata Memorial Hospital, Parel, Mumbai, 400 012, Maharashtra, India.
4MSc, Post graduate student, Department of Nuclear Medicine, Kyungpook National University, Daegu, Republic of Korea, 700-721.
5MSc, Research Assistant, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
6MSc, Research Assistant, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
7MSc, Program Manager, Epidemiology and Clinical Trials Unit, Clinical Research Centre, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai, Maharashtra, India.
8MSc, ad-hoc statistician, Epidemiology and Clinical Trials Unit, Clinical Research Centre, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai, Maharashtra, India.
9MD, Professor and Pathologist, Pathology Department, Tata Memorial Hospital, Parel, Mumbai, 400 012, Maharashtra, India.
10MDS, Professor and Chief, Department of Oral Medicine & Radiology, D.Y. Patil Dental College and Hospital, Sector 7, Nerul, Navi-Mumbai-400706, Maharashtra, India.
11MDS, Professor and Chief, Department of Oral and Maxillofacial Pathology, Ragas Dental College and Hospital, Uthandi, 600096 Chennai, India.
12MS, Professor and Chief, Oral Surgery, Head and Neck Unit, Tata Memorial Hospital, Parel, Mumbai, 400 012, Maharashtra, India.

Article ID: 100001T09SS2014
doi:10.5348/T09-2014-1-OA-1

Address correspondence to:
Sharada Sawant
Vaidya Lab., Advanced Centre for Treatment, Research & Education in Cancer (ACTREC)
Tata Memorial Centre, Kharghar
Navi Mumbai 410 210, Maharashtra
India
Phone: +91 22 27405134
Fax: +91 22 27405085

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How to cite this article
Sharada S, Milind V, Devendra C, Prakash G, Archana S, Siddheshwar R, Sadhana K, Padmavathi A, Shubhada K, Sandeep P, Ranganathan K, Anil DC. Clinicopathological features and prognostic implications of loss of K5 and gain of K1, K8 and K18 in oral potentially malignant lesions and squamous cell carcinomas: An immunohistochemical analysis. Edorium J Tumor Bio 2014;1:1–22.


Abstract
Aims: To analyze alterations in the expression and localization patterns of keratins-K1, K5, K8 and K18 using immunohistochemistry and correlate with clinicopathological parameters of patients with oral potentially malignant lesions and squamous cell carcinomas to evaluate diagnostic and prognostic implications of loss and gain of keratins.
Methods: Altered keratin expression pattern was investigated using immunohistochemistry in tissues of oral normal mucosa (n=10), leukoplakia (n=50), submucous fibrosis (n=67) and tumor respective cut-margins (n=304). The prognostic significance was determined by correlating the values of these two events singly as well as in different permutations and combinations with clinicopathological parameters using univariate and multivariate analyzes.
Results: Loss of K5 and aberrant expression of K1, K8 and K18 were seen in oral premalignant lesions as well as tumor tissues in comparison to normal oral mucosal tissues. Non-expression of K5 (p=0.003), and aberrant expression of K1 (p<0.001), K8 (p=0.001), and K18 (p=0.004), independently significantly correlated with clinicopathological progressive grade of oral premalignant disorders as well as some of the clinicopathological factors of patients with oral cancer. The univariate and multivariate analysis showed the significance of combination of keratin markers (K1, K8, K18) on overall survival and local recurrence free survival of patients with oral cancer. The number of markers combined together has increased the risk of recurrence significantly (p<0.0001).
Conclusion: These findings suggest, loss and gain of keratins could serve as surrogate markers for the diagnosis of oral potentially malignant disorders and may also have prognostic value in patients with oral cancer.

Keywords: Keratin biomarkers, Leukoplakia, Oral squamous cell carcinomas, Submucous fibrosis

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Author Contributions:
Sharada Sawant – Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Critical revision of the article, Final approval of the version to be published
Milind Vaidya – Analysis and interpretation of data, Critical revision of the article, Final approval of the version to be published
Devendra Chaukar – Analysis and interpretation of data, Critical revision of the article, Final approval of the version to be published
Prakash Gangadaran – Acquisition of data, Critical revision of the article, Final approval of the version to be published
Archana Kumari Singh – Acquisition of data, Critical revision of the article, Final approval of the version to be published
Siddheshwar Rajadhyax – Acquisition of data, Drafting the article, Final approval of the version to be published
Sadhana Kannan – Analysis and interpretation of data, Drafting the article, Final approval of the version to be published
Padmavathi A. – Analysis and interpretation of data, Drafting the article, Final approval of the version to be published
Shubhada Kane – Analysis and interpretation of data, Critical revision of the article, Final approval of the version to be published
Sandeep Pagare – Analysis and interpretation of data, Critical revision of the article, Final approval of the version to be published
Ranganathan Kannan – Analysis and interpretation of data, Critical revision of the article, Final approval of the version to be published
Anil D'Cruz – Analysis and interpretation of data, Critical revision of the article, Final approval of the version to be published
Guarantor of submission
The corresponding author is the guarantor of submission.
Source of support
None
Conflict of interest
Authors declare no conflict of interest.
Copyright
© 2014 Sharada Sawant et al. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.



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