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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 1  |  Page : 103-106

Immunohistochemical expression of syndecan-1 in oral dysplastic epithelium


1 Department of Oral Pathology, Al-Ameen Dental College, Bijapur, India
2 Department of Prosthodontics, S. Nijalingappa Institute of Dental Sciences, Gulbarga, India
3 Department of Oral Pathology, Pacific Dental College, Udaipur, India
4 Department of Periodontics, S. Nijalingappa Institute of Dental Sciences, Gulbarga, India
5 Department of Oral Pathology, SVS Institute of Dental Sciences, Mahboobnagar, India

Date of Web Publication23-Apr-2014

Correspondence Address:
B Lakkam
Department of Oral Pathology, Al Ameen Dental College, Bijapur
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.131407

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 > Abstract 

Background: In stratified squamous epithelia, syndecan-1 is proposed to function as a cellto cell adhesion molecule, and plays an important role in regulation of cell growth and differentiation during the developmental process. Oral cancer is a disease with complex etiology, so biological behavior in carcinomas preceded by dysplastic states is difficult to assess and predict its prognosis. Hence, syndecan-1, a recently recognized tumor marker has been proved to be an eminent diagnostic and prognostic tool in assessing biological behavior of various potentially premalignant andmalignant lesions.
Materials and Methods: The study group consisted of 40 specimens of premalignant stateand 10 specimens of normal mucosa.Thesections were stained withhematoxylin and eosin, andimmunohistochemicallyusing syndecan-1 a primary antibody and was observed under light microscope.
Results: Expression decreased with the decreasing grades of dysplasia.
Conclusion: Syndecan-1 can be efficiently used in early detection and diagnosis of oral carcinoma.

 > Abstract in Chinese 

口腔异常增生上皮多配体蛋白聚糖1的免疫组化表达
背景:在分层鳞状上皮细胞中,多配体蛋白聚糖1是具有细胞间黏附功能的分子,并在细胞增长和分化发展过程中起重要的管理作用。口腔癌病因复杂,其生物学行为也难以评估,预后不易判断。因此,多配体蛋白聚糖1,最近发现的一种肿瘤标志物,在评估复杂多样的潜在的可能癌变的和已经癌变的组织中,被证实为一种特别的诊断和提示预后的工具。
材料和方法:研究收集了40例癌前病变的样品和10例正常黏膜样品。用苏木精和曙红染色固定,免疫组化法,在光学显微镜下观察到多配体蛋白聚糖1为首要的抗体。
结论:多配体蛋白聚糖1可有效地用于口腔癌的早期检测和诊断。
关键词:细胞黏附分子,人细胞间黏附分子,恶变,口腔上皮异型增生,鳞状细胞癌,多配体蛋白聚糖


Keywords: Cell adhesion molecule, human intercellular adhesion molecule, malignant transformation, oral epithelial dysplasia, squamous cell carcinoma, syndecan


How to cite this article:
Lakkam B, Majage B, Astekar M, Gugwad R S, Giri G, Ramasahayam S. Immunohistochemical expression of syndecan-1 in oral dysplastic epithelium. J Can Res Ther 2014;10:103-6

How to cite this URL:
Lakkam B, Majage B, Astekar M, Gugwad R S, Giri G, Ramasahayam S. Immunohistochemical expression of syndecan-1 in oral dysplastic epithelium. J Can Res Ther [serial online] 2014 [cited 2019 Oct 22];10:103-6. Available from: http://www.cancerjournal.net/text.asp?2014/10/1/103/131407


 > Introduction Top


In epidermis, keratinocytes are the basal cell layer differentiation. Theylose their attachment to the underlying extracellular matrix and form extensive intercellular adhesions as they stratify. [1] The alterations in adhesion among cell-to-matrix and cell-to-cell required for keratinocyte stratification results from change in expression of numerous adhesion molecules. Syndecan-1, a member of cell surface proteoglycans is known to bind with cell-to-cell and cells-to-interstitial matrix. [2] Interaction between cells and their micro-environment are mediated by adhesion molecules that participate in fundamental biological process, including embryonic development, cell migration, inflammation, and wound healing. [3],[4] Recently, cell-surface carbohydrates have attracted much interest because, essentially all human carcinomas show changes in the synthesis of these structures. [5] These carbohydrates linked to lipids or proteins on the cell membrane are synthesized by a step-wise addition of monosaccharide, each step in this synthesis is catalyzed by highly specific enzymes like glycosyl-transferases. [6]

Syndecan has been suggested to participate in cell-to-cell and cell-to-matrix interaction and of heparan binding growth factors. The primary structures of core protein of four different syndecans, syndecan-1 to syndecan-4 is known to date. [7] De-ranged expression or function of these adhesion molecules has been implicated in tumor pathology and suggested to play a role in tumor development, tumor cell differentiation, invasion, and metastasis. [8],[9] The mechanisms of how specific carbohydrate changes influence on cellular behavior is not precisely known. [10],[11] The purpose of this study was to analyze syndecan-1 expression in dysplastic epithelium of potentially malignant lesions from the oral cavity.


 > Materials and Methods Top


The present study included a total of 50 formalin-fixed paraffin-embedded tissue blocks. It included 10 normal mucosa, 30 specimens of leukoplakia and 10 specimens of oral sub-mucous fibrosis of patients who visited our dental college during a period of 3 months. Amongst the 40 subjects, 26 were males and 14 were females with age ranging from 30-70 years.Two consecutive sections of 3-4 μmeach were cut from the paraffin blocks and stained with hematoxylin and eosin and immunohistochemically with syndecan-1, respectively. The first histological section of potentially malignant lesions thus obtained was re-examined by a pathologist and divided into three histologic grades of differentiation according to the World Health Organization (WHO) classification. The second section was placed on poly l-lysine coated slides and stained using primary syndecan-1 (DAKO Liquid DAB Substrate-Chromogen System) antibody using avidin-biotin immunoperoxidase technique as instructed by the manufacturer. All incubations were performed at room temperature in the humidifying chamber. The specimen slides were not allowed to dry during the staining procedure in order to prevent non-specific staining. Staining intensity for syndecan-l was classified as: '+' as weak staining of tumor cells; '++' as intermediate intensity of staining; '+++' as strong staining. [7],[12] In order to minimize the inter-observer variability all the stained slides were examined by a specialist and an average of theirdiagnosis was obtained. Thus, th e obtained values, were analyzed using Chi-square test usingStatistical Package for the Social Sciences ( SPSS) version 17, computer program [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5] and [Figure 6], [Table 1] and [Table 2].
Figure 1: Hematoxylin and eosin staining of normal mucosa

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Figure 2: Syndecan-1 expression in normal mucosa

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Figure 3: Hematoxylin and eosin staining in a mild dysplasia

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Figure 4: Syndecan-1 expression in mild dysplasia

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Figure 5: Hematoxylin and eosin staining of severe dysplasin in the oral mucosa

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Figure 6: Syndecan-1 expression of severe dysplasia in oral mucosa

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Table 1: The immunohistochemical staining intensity of syndecan-1 among normal and oral dysplastic epithelium

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Table 2: The Statistical analysis of Syndican- 1 expression among the study groups

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 > Results Top


On histopathological examination, 10 cases were suggestive of mild, 9 of moderate, 7 of sever dysplasia, and 4 were diagnosed as carcinoma in situ. Among all the cases of normal mucosa, 100% of them showed strong syndecan-1 immunohistochemical expression. However, among oral dysplastic epithelium, immune-positivity was gradually decreased along with increase in the degree of dysplasia [Table 1].The 10 specimen of oral sub-mucous fibrosis showed minimum change in the expression.


 > Discussion Top


Syndecan-1 is induced during normal differentiation of keratinocytes and its adhesive functions in the cell-to-cell and cell-to-matrix interaction, and is important in maintaining the normal architecture of epithelia. [13],[14],[15] In stratified epithelium, syndecan-1 expression is restricted to epithelial tissues. [7],[16] Syndecan-1 expression is modest in basal layer, strong in spinous and granular layer, and almost absent in the uppermost layer. [17] It appears during four-cell embryos, becomes restricted in pre-implantation embryos to the embryo proper. [18] Syndecan-1 expression undergoes marked changes in expression during epithelial mesenchymal inductive interactions. [19],[20],[21] On embryonic epithelia, it is lost transiently during periods of rapid cell differentiation and permanently upon terminal differentiation. Columnar cell shows weaker staining. [22] On the other hand, the down regulation of syndecan-1 may offer the cell, a possibility to detach and invade. [23],[24],[25] So the role of syndecan-1, can be as a surface marker, in pre-malignant states and its use in carcinoma has been recently established in predicting malignancy rate. [26]

In this study, 2 (22.3%) specimens of mild dysplasia exhibited no change in the distribution of immuno-staining, while staining intensity was slightly decreased or had weak staining in 7 (77.75%) tissue sections. These findings are much in accordance with that of Soukka et al.'s conclusions, as stated in the text book of Berg et al. [6] where in they had found 8 (28.57%) tissue sections exhibiting strong distribution of immunostaining for syndecan-1 and 20 (71.34%) of mild dysplasia exhibited slightly decreased to weak or no staining. With summation of above findings in both the studies larger percentage of specimens were showing weak staining for syndecan-1 with variations in expression.Two (22.3%) specimens of moderate dysplasia showed weak immunostaining only in basal layer and 7 (77.8%) specimens showed weak immunostaining even in basal and suprabasal layer Soukka et al. [6] in their study also found 11 (73.34%) specimens of moderate dysplasia showing weak immunostaining, however, the remaining 4 (26.66%) specimens had strong immunostaining. The variation in immunostaining could be due to larger sample size in their study. Loss of immunopositivity of sundecan-1, especially in the lower part, was commonly observed in moderately dysplastic epithelium in both the studies.

Intermediate to weak immunostaining was observed in 2 (100%) specimens of carcinoma in situ, on the contrary Soukka et al. found only 1 (33.33%) specimen of carcinoma in situ showing weak immunostaining and 2 (66.66%) of them showed strong immunostaining. [6] However, positive areas were detected only at the uppermost cell layer in carcinoma in situ. The difference in variation of percentage of immunostaining may be due to interobserver variability. Soukka et al. with their observation concluded that immunostaining for syndecan-1 decreases with increase in degree of dysplasia. [6] Similar observations were made even in our study. According to Soukka et al.they found that syndecan-1 expression is down-regulated in premalignant lesions of oral epithelium. [6] This decrease in syndecan-1 expression occurs in transformed epithelia and is evident when compared with syndecan-1 expression in normal oral squamous cell epithelium. Syndecan-1 is induced during normal differentiation of keratinocytes and its adhesive functions in the cell-to-cell and cell-to-matrix interactions are important in maintaining the normal architecture of the epithelium.

This study is first of its kind to carry out immunostaining of syndecan-1 on 10 specimen of Oral Submucous Fibrosis (OSMF). Seven (70%) specimens showed strong immunostaining and 3 (30%) specimen showed intermediate immunostaining for syndecan-1.It is interesting to note that 3 (30%) section, which should intermediate immunostaining for syndecan-1, did not show any appreciable dysplastic features under conventional hematoxylin and eosin staining, although percentage of decreased expression of syndecan-1 in overlying epithelium of oral sub-mucous fibrosis is very minimum, but it is worth appreciating feature with use of syndecan-1 immunostaining. So immunohistochemical staining can be used as an adjunct to diagnose the features, which remained unappreciated on hematoxylin and eosin staining in premalignant condition.


 > Conclusion Top


Good amount of syndecan-1 was expressed in normal oral mucosa but altered in pathological states and carcinomas, decreasing in dysplasia and almost absent in malignancy proven also proven statistically significant in different grades, from normal to severe dysplasia showing " P" = 0.000. This study was an attempt in assessing syndecan-1 in certain oral sub-mucous fibrosis showing minimal change in expression suggesting that the main pathology lies in connective tissue resulting in epithelial atrophy. Syndecan-1 helps in early recognition and diagnosis, which will be certainly of utmost help in bringing about the cure.

 
 > References Top

1.Sanderson RD, Hinkes MT, Bernfield M. Syndecan-1, a cell-surface proteoglycan, changes in size and abundance when keratinocytes stratify. J Invest Dermatol 1992;99:390-6.  Back to cited text no. 1
    
2.Anttonen A. Syndecan-1 expression and solublesyndecan-1 in head and neck andlung carcinomas.Academic Dissertation.
Helsinki. :University of Helsinki; 2006.  Back to cited text no. 2
    
3.Morgan MR, Humphries MJ, Bass MD. Synergistic control of cell adhesion by integrins and syndecans. Nat Rev Mol Cell Biol 2007;8:957-69.  Back to cited text no. 3
    
4.Raghow R. The role of extracellular matrix in postinflammatory wound healing and fibrosis. FASEB J 1994;8:823-31.  Back to cited text no. 4
    
5.Geho DH, Bandle RW, Clair T, Liotta LA. Physiological mechanisms of tumor-cell invasion and migration. Physiology (Bethesda) 2005;20:194-200.  Back to cited text no. 5
    
6.Soukka T, Antonen K, Härmä H, Pelkkikangas AM, Huhtinen P, Lövgren T. Highly sensitive immunoassay of free prostate-specific antigen in serum using europium(III) nanoparticle label technology. Clin Chim Acta 2003;328:45-58.  Back to cited text no. 6
    
7.Inki P, Stenbäck F, Grenman S, Jalkanen M. Immunohistochemical localization of syndecan-1 in normal and pathological human uterine cervix. J Pathol 1994;172:349-55.  Back to cited text no. 7
    
8.Ohene-Abuakwa Y, Pignatelli M. Adhesion molecules as diagnostic tools in tumor pathology. Int J Surg Pathol 2000;8:191-200.  Back to cited text no. 8
    
9.Pignatelli M, Vessey CJ. Adhesion molecules: Novel molecular tools in tumor pathology. Hum Pathol 1994;25:849-56.  Back to cited text no. 9
    
10.Pizzo AM, Kokini K, Vaughn LC, Waisner BZ, Voytik-Harbin SL. Extracellular matrix (ECM) microstructural composition regulates local cell-ECM biomechanics and fundamental fibroblast behavior: A multidimensional perspective. J Appl Physiol 2005;98:1909-21.  Back to cited text no. 10
    
11.Wight TN, Kinsella MG, Qwarnström EE. The role of proteoglycans in cell adhesion, migration and proliferation. CurrOpin Cell Biol 1992; 4:793-801.  Back to cited text no. 11
    
12.Rintala M, Inki P, Klemi P, Jalkanen M, Grénman S. Association of syndecan-1 with tumor grade and histology in primary invasive cervical carcinoma. Gynecol Oncol 1999;75:372-8.  Back to cited text no. 12
    
13.Mukunyadzi P, Sanderson RD, Fan CY, Smoller BR. The level of syndecan-1 expression is a distinguishing feature in behavior between keratoacanthoma and invasive cutaneous squamous cell carcinoma. Mod Pathol 2002;15:45-9.  Back to cited text no. 13
    
14.Miettinen HM, Jalkanen M. The cytoplasmic domain of syndecan-1 is not required for association with Triton X-100-insoluble material. J Cell Sci 1994;107:1571-81.  Back to cited text no. 14
    
15.Jalkanen M, Elenius K, Rapraeger A. Syndecan: Regulator of cell morphology and growth factor action at the cell-matrix interface. Trends Glycosci Glycotechn 1993;5:107-20.  Back to cited text no. 15
    
16.Elenius K, Jalkanen M. Function of the syndecans: A family of cell surface proteoglycans. J Cell Sci 1994;107:2975-82.  Back to cited text no. 16
    
17.Tomas D, Vuciæ M, Situm M, Kruslin B. The expression of syndecan-1 in psoriatic epidermis. Arch Dermatol Res 2008;300:393-5.  Back to cited text no. 17
    
18.Bernfield M, Sanderson RD. Syndecan, a developmentally regulated cell surface proteoglycan that binds extracellular matrix and growth factors. Philos Trans R SocLond B Biol Sci 1990;327:171-86.  Back to cited text no. 18
    
19.Thesleff I, Jalkanen M, Vainio S, Bernfield M. Cell surface proteoglycan expression correlates with epithelial-mesenchymal interaction during tooth morphogenesis. Dev Biol 1988;129:565-72.  Back to cited text no. 19
    
20.Vainio S, Jalkanen M, Thesleff I. Syndecan and tenascin expression is induced by epithelial-mesenchymal interactions in embryonic tooth mesenchyme. J Cell Biol 1989;108:1945-53.  Back to cited text no. 20
    
21.Bernfield M, Hooper KC. Possible regulation of FGF activity by syndecan, an integral membrane heparan sulfate proteoglycan. Ann N Y Acad Sci 1991;638:182-94.  Back to cited text no. 21
    
22.Hayashi K, Hayashi M, Jalkanen M, Firestone JH, Trelstad RL, Bernfield M. Immunocytochemistry of cell surface heparan sulfate proteoglycan in mouse tissues. A light and electron microscopic study. J Histochem Cytochem 1987;35:1079-88.  Back to cited text no. 22
    
23.Soukka T, Pohjola J, Inki P, Happonen RP. Reduction of syndecan-1 expression is associated with dysplastic oral epithelium. J Oral Pathol Med 2000;29:308-13.  Back to cited text no. 23
    
24.Leppä S, Vleminckx K, Van Roy F, Jalkanen M. Syndecan-1 expression in mammary epithelial tumor cells is E-cadherin-dependent. J Cell Sci 1996;109:1393-403.  Back to cited text no. 24
    
25.Kato M, Saunders S, Nguyen H, Bernfield M. Loss of cell surface syndecan-1 causes epithelia to transform into anchorage-independent mesenchyme-like cells. Mol Biol Cell 1995;6:559-76.  Back to cited text no. 25
    
26.Vuoriluoto K. Anchor or accelerate: A study on cancer. Doctoral thesis. Department of Pharmacology, Drug Development and Therapeutics, Centre for Biotechnology, University of Turku, VTT Medical Biotechnology, and Turku Graduate School of Biomedical Sciences, Turku, Finland. 2010.  Back to cited text no. 26
    


    Figures

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

  [Table 1], [Table 2]



 

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