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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 2  |  Page : 170-174

Expression of p120-catenin expression in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical study


Department of Oral Pathology and Microbiology, KLE VK Institute of Dental Sciences and Hospital, Belgaum, Karnataka, India

Date of Web Publication29-Sep-2016

Correspondence Address:
Punnya V Angadi
Department of Oral Pathology and Medicine, KLE VK Institute of Dental Sciences and Hospital, Belgaum - 590 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5006.191261

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  Abstract 

Objective: Most oral squamous cell carcinoma (OSCC) are preceded by premalignant conditions that demonstrate histopathologically as epithelial dysplasia and their malignant potential of a lesion is mainly determined using various grading systems. Loss of p120 catenin (p120) or its phosphorylation destabilizes E-cadherin; thereby it regulates cadherin stability and turnover which could affect the cell adhesive and migratory capacity. Therefore, p120 is related to invasiveness and progression of various human epithelial many tumor types, including OSCCs.
Methodology: The immunoexpression of p120 in 60 selected cases were grouped into; oral epithelial dysplasia (OED) (n = 40) and OSCC (n = 20). The cases were assessed by two independent observers. The p120 immunolabeling was analyzed using the parameters intensity, percentage and the location of the epidermal growth factor receptor staining.
Results: In OED, there was p120 expression observed in 100% of cases with 62.5% cases showing preserved expression, i.e., >50%, whereas 15% showed reduced/downregulation of p120 catenin levels. Further, a variation within the grades was also observed. The low-risk group of OED showed a preserved expression seen with most of the cases having >50% expression (95%) positivity and in the high-risk cases, there was a marked reduction with 70% of the cases showing reduced expression (P < 0.01). This reduction in expression was more prominent in OSCC with 60% showing reduced expression, whereas 20% showed loss of expression.
Conclusion: The presence of strong reactivity was seen in oral dysplasia and most of the well-differentiated OSCC, the infiltrating areas of aggressive OSCC showed decreased and/or total lack of immunostaining. The abnormal staining pattern of p120 can reflect loss/reduction of adhesion and could be used to identify the malignant potential of OED and aggressiveness in OED.

Keywords: Oral epithelial dysplasia, oral squamous cell carcinoma, p120 catenin


How to cite this article:
Rajeev A, Angadi PV. Expression of p120-catenin expression in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical study. Indian J Health Sci Biomed Res 2016;9:170-4

How to cite this URL:
Rajeev A, Angadi PV. Expression of p120-catenin expression in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical study. Indian J Health Sci Biomed Res [serial online] 2016 [cited 2022 May 17];9:170-4. Available from: https://www.ijournalhs.org/text.asp?2016/9/2/170/191261


  Introduction Top


It was estimated by GLOBOCAN 2008 that oral cancer accounts for 3-4% of cancers in the world, with oral and pharyngeal carcinoma being the sixth most common and two-thirds of which occurs in the developing countries. [1],[2] In India, contributing factors such as the widespread presence of addictive habits and also due to the cultural diversity, ethnic, geographic factors, the frequency of oral cancer ranks number one regarding incidence among men and third among women. [3]

Oral squamous cell carcinomas (OSCC) survival is highly dependent on the stage of the tumor at diagnosis, and it constitutes around 90% of oral malignancies in the upper aerodigestive tract. As it progresses, Stage I cancers have an 80% 5-year survival rate, while the survival rate decreases to 20% for Stage IV lesions. [2],[3] Most OSCC are preceded by premalignant conditions that demonstrate histopathologically as epithelial dysplasia and their malignant potential of a lesion is mainly determined using various grading systems. [4]

Oral epithelial dysplasia (OED) is a potential precancerous lesion with the risk of progression correlating with the histological grade. According to the World Health Organization 2005, OED is classified based on the cytology and architecture as: Mild, moderate, and severe dysplasia. [5] Considerable inter- and intra-examiner variation have been reported as most the various criteria for diagnosing and grading dysplasia are controversial, highly subjective and open to a wide range of interpretation. Two grade classification (no/questionable/mild - low risk; moderate or severe - implying high risk) of dysplasia was suggested to reduce the ambiguity among pathologists. [1],[6]

p120 catenin (p120) forms a complex with the juxtamembrane domain core region of E-cadherin. [7] The loss of p120 or its phosphorylation destabilizes E-cadherin; thereby it regulates cadherin stability and turnover which could affect the cell adhesive and migratory capacity. p120 is directly related to invasiveness and progression of many human epithelial tumor types, including OSCC. [8],[9]

Despite the literature showing the role of p120 in tumorogenesis in various carcinomas, the role of this molecule has not been identified or studied in OED and only two such studies are found in OSCC.

Hence, this study aims to evaluate and correlate the expression of p120 antibody in various grades of OED and OSCC.

Aim

Evaluation of p120 catenin immunoexpression in OED and OSCC.


  Methodology Top


Sixty selected cases were grouped into; OED (n = 40) and OSCC (n = 20). Two tissue sections from the selected blocks were prepared on a soft tissue microtome (Leica RM2145) of 4 µm thickness and taken onto aminopropyl triethoxy silane coated slides.

One section was stained with hematoxylin and eosin. While the other slide was stained with immunohistochemically using anti - p120 catenin antibody (clone No. EP66; Catalog No. PR062; PathnSitu, Wayne, PA, USA). The standard immunohistochemical protocol was adopted.

A criterion evaluating the immunoexpression for the intensity, location, and percentage was done by using modified Lo Muzio et al. and Zhang et al. technique [Table 1] [Table 2] [Table 3]: [9],[10]
Table 1: Criteria used for intensity


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Table 2: Criteria used for location


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Table 3: Criteria used for percentage of cells with p120 expression


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  Results Top


Comparison of the location, intensity, percentage, and extent of staining within various groups of study [Table 4] [Table 5] [Table 6] [Table 7].
Table 4: Demonstrates the location variation between various study groups


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Table 5: Demonstrates intensity variation between all the study groups


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Table 6: Demonstrates percentage of cells positivity in all study groups


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Table 7: Demonstrates extent variation in all study groups


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When evaluation the location criteria, a progression from membranous staining seen in OED to membranous and cytoplasm seen in OSCC; when comparing the intensity a transition from intense staining in OED to mild and absent staining in OSCC was also noted. On evaluating the percentage of cells that stained positively a progression from preserved staining to 25-50% positivity seen in OED to 1-25% to no positivity in OSCC. The extent criteria are not applicable to carcinoma cases due to loss of function and architecture [Figure 1] [Figure 2] [Figure 3] [Figure 4] [Figure 5] [Figure 6].
Figure 1: Photomicrograph of oral epithelial dysplasia group (×10, extending till granular layer)


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Figure 2: Photomicrograph under high power view showing intense staining (×10)


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Figure 3: Photomicrograph of oral squamous cell carcinoma group showing areas of intense staining (×10)


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Figure 4: Photomicrograph of oral squamous cell carcinoma group showing areas of membranous and cytoplasmic staining (×40)


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Figure 5: Photomicrograph of oral squamous cell carcinoma showing negative staining (×10)


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Figure 6: Photomicrograph of keratin pearls showing absence of stain (×10)


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  Discussion Top


Most OSCC are preceded by clinical premalignant lesions and conditions such as oral leukoplakia, erythroplakia and oral submucous fibrosis characterized histologically by OED. [11]

OED is thus, the histological indicator of potentially malignant lesions whose reported rate of progression to squamous cell carcinoma ranges from 6% to 36%. [8] Usually, grading of OED serves as a basis for the clinician to select the most adequate treatment for the patient taking into consideration that the higher grade OED's have an increased susceptibility for malignant transformation. Although the diagnosis of OED's is made based on morphological analysis, it is of importance to know that all severe dysplasia may not turn to squamous cell carcinoma and paradoxically even a mild dysplasia can become malignant emphasizing the fundamental importance of the knowledge about the molecular pathophysiology of these lesions. Among such molecular changes, cell adhesion molecules play a role. Alteration of normal oral mucosa to dysplasia and eventually to OSCC embodies a complicated process involving varied etiological factors. [1],[12]

In OED there was p120 expression observed in 100% of cases with 62.5% cases showing preserved expression, i.e., >50% while 15% showed reduced/downregulation of p120 catenin levels. Further, a variation within the grades was also observed. The low-risk group of OED, showed a preserved expression seen with most of the cases having >50% expression (95%) positivity and in the high-risk cases, there was a marked reduction with 70% of the cases showing reduced expression (P < 0.01). This reduction in expression was more prominent in OSCC with 60% showing reduced expression whereas 20% showed loss of expression. The findings suggest that alteration in p120 levels are an early change in oral carcinogenesis evident at the premalignant stage and more pronounced in the malignant stage predisposing to loss of cell -cell adhesion and malignant progression [Table 8].
Table 8: Demonstrates the statistical values for difference between OED and OSCC


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A study evaluating the expression of p120, showed that the phosphorylated form was evaluated by in potentially malignant lesions and was classified on the basis of: Weak or no staining in <10% of epithelial cells as low expression of phosphorylated p120-catenin (pp120), and moderate to intense staining in >10% of epithelial cells as high expression of pp120. High membranous expression of pp120 was observed in 11 of 38 (28.9%) patients. They put forward that the potentially malignant oral lesions which expressed high levels of membranous pp120 showed a significantly higher incidence of OSCC than cases expressing low pp120 levels. This is not comparable with our study as this takes into account the phosphorylated form of p120 catenin which has been implicated to affect the cadherin cell adhesion by disassembly of the junction between the epithelial cells. [13]


  Conclusion Top


The presence of strong reactivity in areas of normal epithelium and a similar pattern was seen in oral dysplasia and most of the well-differentiated OSCC, the infiltrating areas of moderately-differentiated showed lower or absent signaling and poorly-differentiated OSCC showed decreased and/or total lack of immunostaining. The abnormal staining pattern of p120 can reflect loss/reduction of adhesion and could be used to identify the malignant potential of OED and aggressiveness in OSCC.

Financial support and sponsorship

Partially sponsored by Colgate-Palmolive Pvt. Ltd.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Seethalakshmi C. Early detection of oral squamous cell carcinoma (OSCC) - Role of genetics: A literature review. J Clin Diagn Res 2013;7:1824-6.  Back to cited text no. 1
    
2.
Byakodi R, Byakodi S, Hiremath S, Byakodi J, Adaki S, Marathe K, et al. Oral cancer in India: An epidemiologic and clinical review. J Community Health 2012;37:316-9.  Back to cited text no. 2
    
3.
Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 2009;45:309-16.  Back to cited text no. 3
    
4.
Diajil A, Robinson CM, Sloan P, Thomson PJ. Clinical outcome following oral potentially malignant disorder treatment: A 100 patient cohort study. Int J Dent 2013;2013:Article ID 809248, 8 pages  Back to cited text no. 4
    
5.
Rastogi V, Puri N, Mishra S, Arora S, Kaur G, Yadav L. An insight to oral epithelial dyslasia. Int J Head Neck Surg 2013;4:74-82.  Back to cited text no. 5
    
6.
Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: Predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med 2008;37:127-33.  Back to cited text no. 6
    
7.
Reynolds AB. Exposing p120 catenin's most intimate affair. Cell 2010;141:20-2. doi: 10.1016/j.cell.2010.03.022.  Back to cited text no. 7
    
8.
Fukumoto Y, Shintani Y, Reynolds AB, Johnson KR, Wheelock MJ. The regulatory or phosphorylation domain of p120 catenin controls E-cadherin dynamics at the plasma membrane. Exp Cell Res 2008;314:52-67.  Back to cited text no. 8
    
9.
Lo Muzio L, Pannone G, Santarelli A, Bambini F, Mascitti M, Rubini C, et al. Is expression of p120ctn in oral squamous cell carcinomas a prognostic factor? Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:789-98.  Back to cited text no. 9
    
10.
Zhang JY, Wang Y, Zhang D, Yang ZQ, Dong XJ, Jiang GY, et al. Delta-catenin promotes malignant phenotype of non-small cell lung cancer by non-competitive binding to E-cadherin with p120ctn in cytoplasm. J Pathol 2010;222:76-88.  Back to cited text no. 10
    
11.
Bouquot J, Speight PM, Farthing PM. Epithelial dysplasia of the oral mucosa - Diagnostic problems and prognostic features. Curr Diagn Pathol 2006;12:11-21.  Back to cited text no. 11
    
12.
van der Waal I, de Bree R, Brakenhoff R, Coebergh JW. Early diagnosis in primary oral cancer: Is it possible? Med Oral Patol Oral Cir Bucal 2011;16:e300-5.  Back to cited text no. 12
    
13.
Ma LW, Zhou ZT, He QB, Jiang WW. Phosphorylated p120-catenin expression has predictive value for oral cancer progression. J Clin Pathol 2012;65:315-9.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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