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| ORIGINAL ARTICLE |
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| Year : 2016 | Volume
: 9
| Issue : 2 | Page : 170-174 |
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Expression of p120-catenin expression in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical study
Aishwarya Rajeev, Punnya V Angadi
Department of Oral Pathology and Microbiology, KLE VK Institute of Dental Sciences and Hospital, Belgaum, Karnataka, India
| Date of Web Publication | 29-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
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2349-5006.191261
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 | |  |
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 | | |
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]
| Results | | |
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 6: Demonstrates percentage of cells positivity 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 | | |
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 | | |
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.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]
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