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      Evaluation of the Ki-67 and MCM3 Expression in Cytologic Smear of Oral Squamous Cell Carcinoma

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          Abstract

          Statement of the Problem:

          Squamous cell carcinoma (SCC) is the most frequent oral cancer whose 5-year survival rate is 80% for early-detected lesions and nearly 30-50% for advanced lesions. Early detection of oral cancers and precancerous lesions can improve the patient’s survival and decrease the morbidity.

          Purpose:

          This study aimed to evaluate and compare the Ki-67 and MCM3 expression in cytologic smear of oral SCC (OSCC).

          Materials and Method:

          We examined 48 oral brush biopsies including 28 OSCC and 20 healthy non-smoking samples. Immunocytochemistry staining was performed for Ki-67 and MCM3 by using an EnVision-labeled peroxidase system, and labeling index (LI) was calculated.

          Results:

          Out of 28 OSCC cases, 27(96.4%) cases contained MCM3 positive cells and 22(78%) cases contained Ki-67 positive cells. All normal mucosa were Ki-67 and MCM3 negative. MCM3 and Ki-67 LI were significantly higher in OSCC than normal mucosa ( p< 0.001). MCM3 LI was significantly higher than Ki-67 LI in OSCC group ( p< 0.001).

          Conclusion:

          Immunocytologic evaluation of Ki-67 and MCM3 can be used for early detection of OSCC. Furthermore, MCM3 may be a more sensitive cytologic biomarker than Ki-67 in SCC patients.

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          Most cited references27

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          Eukaryotic MCM proteins: beyond replication initiation.

          Susan Forsburg (2004)
          The minichromosome maintenance (or MCM) protein family is composed of six related proteins that are conserved in all eukaryotes. They were first identified by genetic screens in yeast and subsequently analyzed in other experimental systems using molecular and biochemical methods. Early data led to the identification of MCMs as central players in the initiation of DNA replication. More recent studies have shown that MCM proteins also function in replication elongation, probably as a DNA helicase. This is consistent with structural analysis showing that the proteins interact together in a heterohexameric ring. However, MCMs are strikingly abundant and far exceed the stoichiometry of replication origins; they are widely distributed on unreplicated chromatin. Analysis of mcm mutant phenotypes and interactions with other factors have now implicated the MCM proteins in other chromosome transactions including damage response, transcription, and chromatin structure. These experiments indicate that the MCMs are central players in many aspects of genome stability.
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            Demographics and occurrence of oral and pharyngeal cancers. The outcomes, the trends, the challenge.

            S. Silverman (2001)
            This article summarizes current trends in the occurrence of, mortality rates associated with and rates of survival of oral and pharyngeal cancer. The author reviewed relevant data and literature on these aspects of oral and pharyngeal cancer, including data from the National Cancer Institute's Surveillance, Epidemiology and End Results program collected from 1973 to 1998. The occurrence of oral and pharyngeal cancer in the United States remains constant, at about 30,000 new cases diagnosed each year. There has been no marked improvement in the five-year survival rates, which remain at about 50 percent, despite advances in surgery and radiation. Detection of early, localized lesions has not improved significantly during the past three decades. There is a minor trend toward a younger age at diagnosis and a slight increase among women. On the basis of epidemiologic data, it appears that the most important approach to decreasing morbidity and mortality associated with oral cancer is increasing early detection of localized lesions combined with appropriate treatment. Concomitantly, aggressive counseling is vital to prevent use and encourage cessation of tobacco and alcohol use. Professional and public education about oral and pharyngeal cancer needs to be improved, and clinicians must emphasize the need for and perform routine oral cancer examinations to promote early diagnosis and treatment.
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              MCM proteins as diagnostic and prognostic tumor markers in the clinical setting.

              Stamatios Theocharis, Philippe Vielh, Stephanie Vgenopoulou … (2010)
              Minichromosome maintenance (MCM) proteins are essential for the process of DNA replication, functioning as license components for the S-phase of cell-cycle initiation and further exerting weak helicase activity to unwind DNA from its supercoiled state at replication forks. The requirement for MCM proteins in cycling cells and their absence in quiescent ones supports evidence for their potential clinical application as cell proliferation markers. In the last few years, aside from their utility as cell proliferation markers, the assessment of MCM expression levels in diverse human malignancies has been the focus of extensive research in an aim to facilitate tumor diagnosis and prognosis in clinical settings. The present article aims to review the available data so far concerning the clinical significance of MCM protein expression in human neoplasia in comparison to conventional proliferative markers. A review of the literature revealed that MCM expression is associated with important clinicopathological parameters for patient management and also exhibits significant diagnostic and prognostic value in several malignancies. MCMs are characterized by higher specificity and sensitivity than the conventional proliferative markers, such as Ki-67 and PCNA, and are thus considered as diagnostic and prognostic tools of greater clinical significance in several types of human malignancy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Dent (Shiraz)
                Journal ID (iso-abbrev): J Dent (Shiraz)
                Title: Journal of Dentistry
                Publisher: Journal of Dentistry Shiraz University of Medical Sciences (Iran )
                ISSN (Print): 2345-6485
                ISSN (Electronic): 2345-6418
                Publication date (Print): September 2017
                Volume: 18
                Issue: 3
                Pages: 207-211
                Affiliations
                [1 ]Oral and Dental Disease Research Center, Dept. of Oral & Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.
                [2 ]Dept. of Oral & Maxillofacial Medicine, School of Dentistry, Shahrekord University of Medical Sciences, Shahrekord, Iran.
                [3 ]Oral and Dental Disease Research Center, Dept. of Oral & Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.
                [4 ]Dept. of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
                [5 ]Otolaryngology Research Center, Dept. of Otorhinolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran.
                Author notes
                Correspondence: Correspondence: Ebrahimi R. Dept. of Oral & Maxillofacial Medicine, School of Dentistry, Shahrekord University of Medical Science, Shahrekord, Iran. Tel:+98-3832326437
                Article
                Publisher ID: JDS-18-3
                PMC ID: 5634361
                SO-VID: b6017530-e80f-4216-9e5e-905f7968405c
                Copyright © Copyright: © Journal of Dentistry Shiraz University of Medical Sciences
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date revision received : August 2016
                Date accepted : September 2016
                Date received : June 2016
                Categories
                Subject: Original Article

                Keywords: squamous cell carcinoma , cytology , biopsy , ki-67 antigen , minichromosome maintenance complex component 3
                Data availability:
                Keywords: squamous cell carcinoma , cytology , biopsy , ki-67 antigen , minichromosome maintenance complex component 3

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