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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2021  |  Volume : 64  |  Issue : 1  |  Page : 22-27
MCM3 proliferative index is worthier over Ki-67 in the characterization of salivary gland tumors


1 Department of Oral Pathology and Microbiology, ITS-CDSR, Muradnagar, Ghaziabad, India
2 Department of Pathology, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India
3 Department of Oral Pathology, Microbiology, and Forensic Odontology, Dental Institute, RIMS, Ranchi, Jharkhand, India

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Date of Submission24-Jan-2020
Date of Decision24-Feb-2020
Date of Acceptance27-Apr-2020
Date of Web Publication8-Jan-2021
 

   Abstract 


Background: Salivary gland tumors bear uncanny characteristics of being different based on their morphological aspects rather than the presence of clear demarcation. This ambiguity in the spectrum from benign to malignant salivary gland neoplasms while categorizing the neoplasm is having inherent pitfalls. The present study was, therefore, designed to characterize benign and malignant salivary gland tumors based on their proliferative indices. Materials and Method: Study samples comprised of 97 cases of histopathologically confirmed benign and malignant salivary gland tumors. The cases were immunohistochemically assessed for MCM3 and Ki-67 expressions and the molecular characterization was performed based on the findings. Results: The majority of benign and malignant salivary gland tumors were from the parotid gland, (51.2%) and (42.4%), respectively. Overall mean labeling index of MCM3 was higher i.e., (5.60 ± 3.99) in comparison to Ki-67 i.e., (2.82 ± 3.14) with P = 0.05 using paired t-test. Besides, malignant salivary gland neoplasms represented a higher mean score of MCM3 and Ki-67 than benign neoplasms. Conclusion: The requirement of a novel marker has led to the use of MCM3 which has a characteristic role in the entire spectrum of the cell cycle. The present study highlighted the extrapolation of MCM3 over Ki-67 for diagnosis and for true characterization of biologic behavior of salivary gland pathologies which may, in turn, influence the treatment modality employed for such lesions.

Keywords: MCM3, neoplasms, Ki-67, salivary gland

How to cite this article:
Raja R, Shetty DC, Chandrakanta, Juneja S, Tandon A, Gulati N. MCM3 proliferative index is worthier over Ki-67 in the characterization of salivary gland tumors. Indian J Pathol Microbiol 2021;64:22-7

How to cite this URL:
Raja R, Shetty DC, Chandrakanta, Juneja S, Tandon A, Gulati N. MCM3 proliferative index is worthier over Ki-67 in the characterization of salivary gland tumors. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Jan 21];64:22-7. Available from: https://www.ijpmonline.org/text.asp?2021/64/1/22/306528





   Introduction Top


Salivary gland tumors (SGTs) are one of the most complex human neoplasms, demonstrating variations in the clinicopathological profile.[1] The sheer variety of tumor types and the rarity of these tumors pose challenges in devising a highly predictive grading scheme.[2] Salivary gland carcinomas comprise 3–5% of all head and neck malignancies, yet they are the most diverse with many different types recognized by the World Health Organization (WHO).[3] The development of SGTs is constituted by the same population of cells (i.e, luminal, and abluminal) which attain different histopathological patterns and are graded accordingly. Because it is the “form” of a neoplasm that is assessed histologically and on which diagnosis is based, classifying SGTs based on histological patterns, and clinicopathological correlates is practical and pragmatic. The oncogenesis of SGTs is characterized not just by the progression of changes at the cellular level but also at the genetic, epigenetic, and molecular levels.[4]

The Ki-67 antigen which is a proliferative marker occurs in the G1 phase where there is a subsequent increase in Ki-67 protein. Ki-67 is not expressed in cells showing an arrest in the cell cycle and starts expressing in S phase, progressively increasing through S and G2 phases which reaches a plateau at mitosis as appropriate stimulation. If no proper stimulation to proliferate is received, then the cell enters G0 and production of the Ki-67 protein drops to an undetectable level. This marker rapidly disappears after mitosis and the half-life of the detectable antigen is 1 h or less.[5] On the other hand, MCM3 (minichromosome maintenance 3) protein plays a crucial role in the initiation and elongation of DNA replication and progression of the cell cycle. The difference between the MCM3 and Ki-67 can be explained by the differential expression of these markers in the cell cycle in which MCM3 expressed during the long interval of the cell cycle. Therefore, the proportion of epithelial tumoral cells that are in primed replication state can be detected by MCM3 suggesting it to be more sensitive and specific.[1],[6] As most of the diagnostic criteria are incomplete and tumor subtypes are numerous; the present study was undertaken to characterize benign and malignant SGTs based on the proliferative index using MCM3 and Ki-67 expression and to correlate it with histopathological features and biological behavior of SGTs which will surely help to ascertain the biologic potential of SGTs and may further have prognostic and therapeutic implications.[2]


   Materials and Method Top


The study was conducted on archival tissue samples which were submitted for histopathological analysis from the department of Oral Pathology and Microbiology, ITS-CDSR, Muradnagar, Ghaziabad and Department of Pathology, Sarojini Naidu Medical College, Agra after gaining consent from Institutional Ethics Committee, ITS-CDSR, Muradnagar, Ghaziabad. The samples were fixed in 10% neutral buffered formalin and embedded in paraffin wax to obtain 3μ sections for immunohistochemistry procedure. Study samples consisted of a total of 97 cases of histopathologically confirmed benign and malignant SGTs. Clinical data such as age, gender, and location were also recorded for each case. Ethical approval from the institutional review board was obtained for this study. The histopathology categorization was performed using WHO classification as benign and malignant [Figure 1]a,[Figure 1]b,[Figure 1]c,[Figure 1]d.
Figure 1: Histopathological presentation of Pleomorphic adenoma (a); Carcinoma-ex pleomorphic adenoma (b); Adenoid cystic carcinoma (c); and Mucoepidermoid carcinoma (d) (H and E,10×; inset 40×)

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About 3μ thick sections from archival formalin-fixed paraffin-embedded tissues were placed on poly-L-lysine coated slides for immunohistochemical analysis. MCM3 and Ki-67 expressions were analyzed by immunohistochemical examination with antibodies. The deparaffinized sections were boiled in a pressure cooker with 0.01 M of trisodium citrate buffer (retrieval solution) at pH 6.2 for retrieval of Ki-67 and in Tris-buffered saline at pH 9 for retrieval of MCM3 for cycles of 95°C and 98°C for 8 and 5 min, respectively. The slides were allowed to cool in respective buffers for 30 min and washed in distilled water. Immunohistochemical staining for these proteins was performed by the avidin-biotin complex peroxidase kits. Primary monoclonal anti-MCM3 antibody (Santa Cruz Biotechnology Cat. No: SC-390480; Lot No. K1213) and monoclonal anti-Ki-67 antibody (Biogenex Inc.; Cat. No: AM 297-5M; Lot No. AM 2971214) along with secondary antibody-poly- HRP secondary detection system (Biogenex Ind Pvt Ltd) were used. For MCM3, normal buccal mucosa served as a positive control, and for Ki-67, oral squamous cell carcinoma was taken as a positive control. Positive staining for MCM3 was identified as crisp brown color in the nuclei of the basal layer of normal buccal mucosa whereas positive staining for Ki-67 was selectively identified as crisp nuclear staining within tumor cells in oral squamous cell carcinoma [Figure 2].
Figure 2: Positive staining for MCM3 (10×) in the nuclei of the basal layer of normal buccal mucosa (a) and positive staining for Ki-67 (10×) within tumor cells in oral squamous cell carcinoma (b)

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Immunoscoring of cell positivity and intensity for MCM3 and Ki-67 were done from the analysis of 1000 cells from 5 randomly selected fields using a grid. Qualitative scoring was done as {+,++,+++} mild, moderate, and intense. For the quantitative score, the immunoreactive score was evaluated by counting the number of positive nuclei for MCM3 and Ki-67 per 1000 tumor cells of all cases, and further, the percentage of positive cells was calculated.[7]


   Results Top


Statistical analysis was done using Statistical Package for Social Sciences (SPSS) v. 20. Data were expressed as mean and standard deviation. Differences between the different variables were analyzed using the ANOVA test, t-test, and post Hoc test followed by the Bonferroni test. Besides this, area under the curve values was calculated by applying the receiver operating characteristic (ROC) curve analysis for both the molecules. Pearson's Chi-square test was carried out to determine the level of correlation or association between the groups under study. P = 0.05 was considered significant.

Most of the SGTs were present in patients 50 years of age amongst which 95.1% of patients presented with benign SGTs. However, the majority of malignant SGTs (57.6%) were present in patients 50 years of age. Both benign and malignant tumors showed a higher predilection in females (65.9% and 55.9%, respectively). The majority of benign and malignant SGTs were from the parotid gland, (51.2%) and (42.4%) respectively, followed by palatal region (40.7%), tongue (6.8%), and submandibular and retromolar regions (3.4%).

The immunoexpression score of MCM3 and Ki-67 concerning the molecular characterization of benign and malignant SGTs revealed that the mean MCM3 and Ki-67 immune scores for benign SGTs were (3.43 ± 2.3) and (1.72 ± 1.8), respectively in comparison to malignant SGTs (7.11 ± 4.2) and (3.37 ± 3.5). Overall mean labeling index of MCM3 was higher i.e., (5.60 ± 3.99) in comparison to Ki-67 i.e., (2.82 ± 3.14) with P = 0.05 using paired t-test. The sensitivity and specificity of MCM3 and Ki-67 are depicted by ROC curve whereby the area under the graph for MCM3 immunoexpression was 77.3% (with standard error as 0.064), and for Ki-67 immunoexpression was 62.5% (with standard error as 0.069), predicting MCM3 to be a sensitive and specific marker as compared to Ki-67 [Graph 1].



The mean scores of MCM3 and Ki-67 immunoscoring in Pleomorphic adenoma were based on the histopathologic features. Out of 41, 21 cases were cell-rich with a mean score of MCM3 (4.00 ± 2.3) and Ki-67 (2.49 ± 1.5), respectively and 20 cases were stroma rich with a mean score of MCM3 (2.82 ± 2.3) and Ki-67 (1.19 ± 1.8), respectively [Table 1].
Table 1: Correlation of MCM3 and Ki-67 immunoscoring with histopathological features in benign salivary gland tumors

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The mean score of MCM3 and Ki-67 expression with histopathological features of malignant SGTs (carcinoma-ex-pleomorphic adenoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma) was also assessed. Carcinoma-ex-pleomorphic adenoma cases were evaluated for the presence/absence of necrosis, anaplasia, and capsular invasion. Only 4 out of 19 cases presented with necrosis and mean labeling index of 15.8 ± 2.7 for MCM3 and 13.6 ± 0.00 for Ki-67, respectively. Besides, 16 cases with anaplasia along with 14 cases which showed capsular invasion significantly (P = 0.05) revealed higher mean labeling indices for MCM3 over Ki-67, respectively [Table 2].
Table 2: Correlation of MCM3 and Ki 67 immunoscoring with histopathological features in malignant salivary gland tumors

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Out of 21 cases of mucoepidermoid carcinoma which were analyzed for anaplasia, cystification, and necrosis; 11 cases presented with anaplasia with mean labeling index of MCM3 (7.3 ± 1.8) and Ki-67 (4.1 ± 1.8), respectively. Similarly, 12 cases showed 25% cystification with mean labeling index of MCM3 (7.13 ± 1.9) and Ki-67 (4.18 ± 1.6) and 9 cases revealed 25% cystification with mean labeling index of MCM3 (2.5 ± 1.9) and Ki-67 (0.7 ± 1.2). Only 1 case presented necrosis with the higher index for MCM3 [Table 2].

A total of 16 cases of adenoid cystic carcinoma were evaluated for the type of histopathological patterns, necrosis, and anaplasia. About 6 cases showed a cribriform pattern with mean labeling index of (3.25 ± 1.8) and Ki 67 (1.6 ± 1.4) and 8 cases showed a tubular pattern with mean labeling index of (5.3 ± 1.5) and Ki 67 (2.06 ± 1.7). Only 2 cases revealed a solid pattern with a mean labeling index of (6.9 ± 0.42) and Ki 67 (0.0 ± 1.5). Among 3 cases that showed necrosis and 11 cases that showed anaplasia, the indices were higher for MCM3 [Table 2].


   Discussion Top


SGTs comprise 5% of all head and neck neoplasms.[8] As suggested by Barnes et al.,[9] around 80% of all SGTs are located within the parotid gland and are mostly benign except for 15–30% cases which are malignant. In SGTs, although the gold standard of diagnosis remains histopathological examination[8],[10]; proliferation markers such as Ki-67, AgNORs, p27, MCM protein provide a diagnostic and prognostic aid and are gaining relevance for grading SGTs as high or low risk. Ki67, a commonly-used proliferative marker, is not expressed in cells entering G1 from the G0 phase but is only expressed in actively dividing cells.[11] Ki-67 is present in the nuclei of cells in the G1, S, and G2 phases of the cell cycle of dividing cells, as well as in mitosis. This marker rapidly disappears after mitosis and the half-life of the detectable antigen is 1 h or less.[12],[13] In contrast to Ki67, MCM is significantly highly expressed in the G1 and S phases of the cell cycle, so it can potentially be used to detect cells entering G1 from the G0 phase.[11] Therefore, the assessment of cell proliferation needs other markers that directly regulate DNA replication. Hence MCM proteins could be used as a novel marker for proliferating cells.[13] The MCM proteins play a crucial role in the initiation and elongation of DNA replication and progression of the cell cycle. They interact with each other at the early stage of DNA synthesis and form a stable hetrohexamer with DNA helicase activity functioning in the DNA replication of eukaryotic cells.[14]

PCNA, another widely used marker, is involved not only in DNA replication, but also in its repair, and may thus be present in large quantities when cells are not actively proliferating. In contrast, MCM proteins are related only to the replication of DNA. Thus, MCM proteins may have higher accuracy than the traditional markers Ki67 and PCNA in assessing cellular proliferative activity.[11],[15] The expression of other cell proliferation markers such as MCM and geminin expression in gastric carcinomas is higher than in normal tissue and adenomas. Besides, the expression of topo IIα in gastric carcinoma and endometrial adenocarcinoma has been reported.[15]

To evaluate the role of proliferative markers in the diagnosis of SGTs, we performed Ki-67 and MCM3 and analyzed them both quantitatively and qualitatively. It was observed that the mean labeling indices for malignant SGTs were higher than benign tumors for both the markers which are as per the findings of Aashkvandi et al.[1] and Abdalla et al.,[6] whereas Zelinski et al.[16] proved the same but in adolescent age groups. Yang et al.[17] also proved the same in papillary thyroid carcinomas. Various studies[18],[19],[20],[21],[22] have suggested that MCM protein predicts better prognosis than Ki-67 in oral cavity squamous cell carcinomas.

On the assessment of the qualitative index of both the markers; benign tumors demonstrated mild-to-moderate staining whereas in malignant tumors the staining was moderate-to-intense. The findings were as per Muhammad et al.[7] and Munteanu et al.[23] The sensitivity and specificity of both molecules were calculated using ROC curve which revealed that MCM3 immunoexpression was 77.3% (with standard error as 0.064), and for Ki-67 immunoexpression was 62.5% (with standard error as 0.069), predicting MCM3 to be a sensitive and specific marker as compared to Ki-67 for molecular characterization between benign and malignant salivary gland neoplasms.

Most gradings are usually done “intuitively” using general cytomorphologic features (pleomorphism, mitoses, necrosis) and are thus highly individualized that the histologic tumor grade ranks highly among the most important predictors of outcome for salivary gland neoplasms. Foot and Frazell,[24] used various histopathological criteria to grade SGTs and divided them into cell-rich and stroma rich subtypes. We also compared the expression of MCM3 and Ki-67 with histopathological features (cell-rich and stroma rich) in benign tumors. It is believed that cell-rich subtype is more increasingly associated with the extension to the capsule and surrounding tissue and they have an increased tendency for recurrence. The mean labeling score of MCM3 (2.7 ± 1.9) and Ki-67 (4.1 ± 1.8) was comparatively higher in cell-rich type. These findings indicate the higher proliferative activity of the tumor in cell-rich cases in comparison to stroma rich type [Figure 3]a and [Figure 3]b.
Figure 3: MCM3 (a) and Ki-67 (b) expressions in Pleomorphic adenoma; MCM3 (c) and Ki-67 (d) expressions in carcinoma-ex-pleomorphic adenoma; MCM3 (e) and Ki-67 (f) expressions in adenoid cystic carcinoma; MCM3 (g) and Ki-67 (h) expressions in mucoepidermoid carcinoma. (10x)

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According to Spiro et al.,[25] Seethla et al.[3] and Bhavani et al.[26]; pleomorphism, anaplasia, necrosis, mitosis, capsular invasion, etc., are the criteria to be followed with invasive cells showing focal features of classical Pleomorphic adenoma with extensive areas of hyalinization, as one of the prime criteria for the diagnosis of carcinoma-ex- pleomorphic adenoma which also represents the malignant transformation of a preexisting pleomorphic adenoma, usually in the setting of an untreated, longstanding benign Pleomorphic adenoma, or in a tumor with multiple local recurrences. In our study, the cases with necrosis had a higher mean labeling index of MCM3 (15.8 ± 2.7) and Ki-67 (13.6 ± 0.00) in comparison to cases in which necrosis was absent. Similarly, the cases with anaplasia and capsular invasion presented higher mean labeling indices [Figure 3]c and [Figure 3]d. The findings were following the studies conducted by Kitayama et al.[27] However, Palma et al.[28] proved the same with the aid of other proliferative markers such as HER-2, p53 protein, and Mib-1.

In our study, out of 16 cases of adenoid cystic carcinoma 6 cases showed a cribriform pattern with mean labeling index of MCM3 (3.25 ± 1.8) and Ki-67 (1.6 ± 1.4), 8 cases showed a tubular pattern with mean labeling index of MCM3 (5.3 ± 1.5) and Ki-67 (2.06 ± 1.7) and only 2 cases showed a solid pattern with mean labeling index of MCM3 (6.9 ± 0.42) and Ki-67 (0.0 ± 1.5). Furthermore, cases with necrosis and anaplasia had higher mean labeling indices of MCM3 and Ki-67 [Figure 3]e and [Figure 3]f. This was following the study done by Jeng et al.,[29] Vered et al.,[30] and Ettl et al.[31] who proved a solid pattern of adenoid cystic carcinoma to be the most aggressive with poor prognosis using other markers such as c- kit and EGFR. Our studies are consistent with Faur et al. who have used a combination of Ki-67 and p53 as proliferative markers to assess the biological behavior of various tumors and also Suzzi et al. who have used Ki-67 and Mib1 exclusively in malignant SGTs. Similarly, Tadbir et al. investigated Ki-67 and CD 105 as proliferation and angiogenetic markers in SGTs which further pointed towards the aggressive behavior of malignant SGTs.

According to Armed Forces Institute of Pathology (AFIP) and Brandwein system, mucoepidermoid carcinoma is histologically characterized by cystic contents i.e., 25% and 25% cystification, mitosis, pleomorphism, tumor nests, anaplasia, necrosis, etc., to grade the tumor and to know the aggressive behavior of the lesion. The mean labeling score of MCM3 and Ki-67 (7.3 ± 1.8) and (4.1 ± 1.8), respectively which was higher in cases in which anaplasia was present. This was following the study by Namboodiripad et al.[32] [Figure 3]g and [Figure 3]h.

In conclusion, SGTs bear uncanny characteristics of appearing as different tumors based on morphological aspects rather than clear demarcation present in other neoplasms related to anaplasia. This ambiguity in the spectrum from benign to malignant salivary gland neoplasms while categorizing the neoplasm is having inherent pitfalls. The results obtained with Ki-67 could be variable due to its multifold expression as it is expressed during initiation along with cells undergoing apoptosis along with a situation when DNA synthesis is negated and blocked. The pursuit of a novel marker has finally led to the use of MCM3 which has a characteristic role in the entire spectrum of the cell cycle. The present study has highlighted the extrapolation of MCM3 over Ki-67 from not only diagnostic but also from a prognostic point of view. Since it has been mentioned that diagnosis would not be the future mainstay for SGTs, due to huge transgression between benign and malignant neoplasms and very subtle variations in their behavior, a more accurate molecule like MCM3 could be used for bridging the gap and exploring prognostic validation, which is long desired in SGTs.

Key points

  • Both MCM3 and Ki-67 are overexpressed in malignant salivary gland neoplasms which correlates with their aggressiveness.
  • Both MCM3 and Ki-67 were overexpressed in cell rich variants as compared to stroma rich variants of pleomorphic adenoma.
  • MCM3 and Ki-67 immunoexpression was higher in cases with anaplasia, necrosis and cystification in mucoepidermoid carcinoma.
  • MCM3 and Ki-67 immunoexpression correlated with presence of necrosis, anaplasia and capsular invasion in cases of carcinoma-ex-pleomorphic adenoma.
  • MCM3 and Ki-67 labelling indices were highest in solid pattern as compared to cribriform and tubular pattern in cases of adenoid cystic carcinoma.
  • Based on ROC curve, MCM3 is more sensitive and specific marker for assessing proliferative activity of benign and malignant salivary gland tumors.


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Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Ashkavandi ZJ, Najvani AD, Tadbir AA, Pardis S, Ranjbar MA, Ashraf MJ. MCM3 as A novel diagnostic marker in benign and malignant salivary gland tumors. Asian Pac J Cancer Prev 2013;14:3479-82.  Back to cited text no. 1
    
2.
Pusztaszeri MP, Faquin WC. Update in salivary gland cytopathology: Recent molecular advances and diagnostic applications. Semin Diagn Pathol 2015;32:264-74.  Back to cited text no. 2
    
3.
Seethala RR. An update on grading of salivary gland carcinomas. Head Neck Pathol 2009;3:69-77.  Back to cited text no. 3
    
4.
Linda X, Yin BA, Patrick K. Genetic alterations in salivary gland cancers. Int J Cancer 2016;122:1822-31.  Back to cited text no. 4
    
5.
Birajdar SS, Radhika M, Paremala K, Sudhakara M, Soumya M, Gadivan M. Expression of Ki-67 in normal oral epithelium, leukoplakic oral epithelium and oral squamous cell carcinoma. J Oral Maxillofac Pathol 2014;18:169-76.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Abdalla RM, Abany EL, Ramadan OR, Habib MA. Expression of MCM3 and Ki- 67 as diagnostic markers in benign and malignant salivary gland tumors. Alexandria Dent J 2015;40:248-55.  Back to cited text no. 6
    
7.
Muhammad L, Mousa C, Abdulqadir H. Proliferative potential in benign mixed salivary gland tumors, using Ki67 marker in relation to different clinicopathological parameters. Zanco J Med Sci 2016;20:1-6.  Back to cited text no. 7
    
8.
Speight P, Barrett A. Salivary gland tumors. Oral Dis 2004;8:229-40.  Back to cited text no. 8
    
9.
Barnes L, Eveson JW, Riechart PA. Surgical Pathology of the Head and Neck, Int Agency Fr Res on Cancer. 3rd ed.; 2005. p. 475 608.  Back to cited text no. 9
    
10.
Nurhan G, Nil C, Fatih C. Ki-67 and MCM-2 in dental follicle and odontogenic cysts: The effects of inflammation on proliferative markers. Sci World J 2010;6:1-6.  Back to cited text no. 10
    
11.
Juríková M, Danihel L, Polák Š, Varga I. Ki67, PCNA, and MCM proteins: Markers of proliferation in the diagnosis of breast cancer. Acta Histochem 2016;118:544-52.  Back to cited text no. 11
    
12.
Van Oijen MG, Medema RH, Slootweg PJ, Rijksen G. Positivity of the proliferation marker Ki-67 in noncycling cells. Am J Clin Pathol 1998;110:24-31.  Back to cited text no. 12
    
13.
Alison MR, Hunt T, Forbes SJ. Minichromosome maintenance (MCM) proteins may be pre-cancer markers. Gut 2002;50:290-1.  Back to cited text no. 13
    
14.
Forsburg SL. Eukaryotic MCM proteins: Beyond replication initiation. Microbiol Mol Biol Rev 2004;68:109-31.  Back to cited text no. 14
    
15.
Kimura F, Okayasu I, Kakinuma H, Satoh Y, Kuwao S, Saegusa M, et al. Differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells using the cell proliferation markers minichromosome maintenance protein 7, geminin, topoisomerase II alpha and Ki-67. Acta Cytol 2013;57:384-90.  Back to cited text no. 15
    
16.
Zielinski R, Kobos J, Zakrzewska A. Comparison between immunohistochemical expression of Ki-67 and MCM-3 in major salivary gland epithelial tumors in children and adolescents. Preliminary study. Pol J Pathol 2016;67:351-6.  Back to cited text no. 16
    
17.
Yang C, Wen Y, Li H, Zhang D, Zhang N, Shi X, et al. Overexpression of minichromosome maintenance 2 predicts poor prognosis in patients with gastric cancer. Oncol Rep 2011;27:135-42.  Back to cited text no. 17
    
18.
Kodani I, Shomori K, Osaki M, Kuratate I, Ryoke K, Ito H. Expression of minichromosome maintenance 2(MCM2), Ki-67 and cell-cycle- related molecules, and apoptosis in the normal-dysplasia-carcinoma sequence of the oral mucosa. Pathobiology 2001;69:150-8.  Back to cited text no. 18
    
19.
Meng MV, Grossfeld GD, Williams GH, Dilworth S, Stoeber K, Mulley TW, et al. Minichromosome maintenance protein 2 expressions in prostate: Characterization and association with outcome after therapy for cancer. Clin Cancer Res 2001;7:2712-8.  Back to cited text no. 19
    
20.
Gonzalez MA, Pinder SE, Callagy G, Vowler SL, Morris SS, Bird K, et al. Minichromosome maintenance protein 2 is a strong independent prognostic marker in breast cancer. J Clin Oncol 2003;21:4306-13.  Back to cited text no. 20
    
21.
Korkolopoulou P, Givalos N, Saetta A, Goudopoulou A, Gakiopoulou H, Thymara I, et al. Minichromosome maintenance proteins 2 and 5 expressions in muscle-invasive urothelial cancer: A multivariate survival study including proliferation markers and cell cycle regulators. Hum Pathol 2005;36:899-907.  Back to cited text no. 21
    
22.
Szelachowska J, Dziegiel P, Jelen-Krzeszewska J, Jelen M, Matkowski R, Pomiencko A, et al. MCM-2 protein expression predicts prognosis better than Ki-67 antigen in oral cavity squamocellular carcinoma. Anticancer R 2006;26:2473-8.  Back to cited text no. 22
    
23.
Munteanu MC, Margaritescu C, Cionca L, Nitulescu NC, Daguci L, Ciuca EM. Acinic cell carcinoma of the salivary glands: A retrospective clinicopathologic study of 12 cases. Rom J Morphol Embryol 2012;53:313-20.  Back to cited text no. 23
    
24.
Foote F, Frazell E. Tumors of the major salivary glands. Cancer 1953;6:1065-133.  Back to cited text no. 24
    
25.
Spiro RH. Salivary neoplasms: Overview of a 35-year experience with 2807 patients. Head Neck Surg 1986;8:177-84.  Back to cited text no. 25
    
26.
Bhavani K, Ran U, Venkatraman J. Histopathological study of salivary gland tumours. J Evolution Med Dent Sci 2016;5:5240-4.  Back to cited text no. 26
    
27.
Kitayama T, Kunimura T, Sugiyama T, Omatsu M, Arima S, Mori T, et al. Immunohistochemical features of an Atypical Pleomorphic Adenoma of the salivary Gland- Overexpression of Ki 67 and P 53. J Med Sci 2009;21:311-7.  Back to cited text no. 27
    
28.
Palma S. Carcinoma ex pleomorphic adenoma, with particular emphasis on early lesions. Head Neck Pathol 2013;7:68-76.  Back to cited text no. 28
    
29.
Jeng Y, Lin C, Hsu H. Expression of the c-kit protein is associated with certain subtypes of salivary gland carcinoma. Cancer Lett 2000;154:107-11.  Back to cited text no. 29
    
30.
Vered M, Braunstein E, Buchner A. Immunohistochemical study of epidermal growth factor receptor in adenoid cystic carcinoma of salivary gland origin. Head Neck 2002;24:632-6.  Back to cited text no. 30
    
31.
Ettl T, Schwarz S, Kleinsasser N, Hartmann A, Reichert TE, Driemel O. Overexpression of EGFR and absence of c-kit expression correlate with poor prognosis in salivary gland carcinoma. Histopathology 2008;53:567-77.  Back to cited text no. 31
    
32.
Namboodiripad PC. Immunological markers for malignant salivary gland tumors. J Oral Biol Craniofac Res. 2014;4:127-34.  Back to cited text no. 32
    

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Correspondence Address:
Ankita Tandon
Associate Professor, Department of Oral Pathology, Microbiology and Forensic Odontology, Dental Institute, RIMS, Ranchi, Jharkhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_63_20

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