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Immunohistochemical Characteristics Of Original Article doi: 10.5146/tjpath.2014.01298 Immunohistochemical Characteristics of Cystic Odontogenic Lesions: A Comparative Study Kistik Odontojenik Lezyonların İmmünohistokimyasal Özellikleri: Karşılaştırmalı Bir Çalışma Ayhan ÖZcaN, İbrahim YAVAN, Ömer GÜNHAN Department of Pathology, Gülhane Military Medical Academy, School of Medicine, ANKARA, TURKEY ABSTRACT ÖZ Objective: Cystic ameloblastoma, keratocystic odontogenic tumor, Amaç: Kistik ameloblastoma, keratokistik odontojenik tümör, dentigerous cyst, and radicular cyst are the most commonly dentijeröz kist ve radiküler kist en sık karşılaşılan kistik odontojenik encountered cystic odontogenic lesions. The aim of this study was lezyonlardır. Çalışmada bu lezyonlarda survivin, E-cadherin, CD138 to investigate the expressions of survivin, E-cadherin, CD138, and ve CD38 ekspresyonları ve bunların potansiyel tanısal kullanımları CD38 in these lesions and their potential diagnostic usage. araştırılmıştır. Material and Method: A total of 20 cases, consisting 5 radicular Gereç ve Yöntem: Çalışma serimiz 5 kistik ameloblastoma, 5 cysts, 5 dentigerous cysts, 5 keratocystic odontogenic tumors and keratokistik odontojenik tümör, 5 dentijeröz kist ve 5 radiküler kist 5 cystic ameloblastomas were included in our series. For all cases, olmak üzere toplam 20 olgudan oluşmaktadır. Bütün olgulara ait sections from the selected blocks were stained against the antibodies seçilmiş bloklardan sağlanan kesitler otomatize bir cihazda survivin, for survivin, E-cadherin, CD138, and CD38 on an automated device. E-cadherin, CD138, and CD38 antikorları ile boyandı. Results: All cystic ameloblastomas and keratocystic odontogenic Bulgular: Kistik ameloblastoma ve keratokistik odontojenik tumors showed diffuse and strong nuclear survivin expression. tümörlerin hepsi yaygın ve kuvvetli nükleer survivin ekspresyonu No specific survivin immunoreactivity was observed in the gösterdi. Dentijeröz ve radiküler kistlerde spesifik survivin dentigerous and radicular cysts. E-cadherin expression was stronger ekspresyonu gözlenmedi. E-cadherin ekspresyonu diğer lezyonlarla in all dentigerous cysts and radicular cysts when compared to karşılaştırıldığında, dentijeröz ve radiküler kistlerde daha belirgindi. others. CD138 expression in stromal cells was prominent in cystic CD138 ekspresyonu kistik ameloblastomalarda stromal hücrelerde ameloblastomas, but gradually decreased in the other three lesions. daha belirgindi, ancak diğer lezyonlarda giderek azalan oranlardaydı. All cases were negative for CD38. CD38 olguların hepsinde negatifdi. Conclusion: In the present study, loss of E-cadherin expression in Sonuç: Çalışmada, keratokistik odontojenik tümörlerde ve kistik epithelial cells, strong CD138 expression in stromal cells and strong ameloblastomada epitelyal hücrelerde E-cadherin kaybı, stromal nuclear survivin expression both in epithelial and stromal cells in hücrelerde kuvvetli CD138 ekspresyonu ve hem epitelyal hem cystic ameloblastomas and keratocystic odontogenic tumors were the de stromal hücrelerde kuvvetli nükleer survivin ekspresyonu most remarkable findings. These findings are also reinforced by the en karakteristik bulgulardır. Bu bulguların bu tür lezyonların studies suggesting their role in the aggressiveness and pathogenesis patogenezini ve agresif davranışındaki rolünü de gösterecek of these tumors. çalışmalarla güçlendirilmesi gerekmektedir. Key Words: Odontogenic tumors, Odontogenic cysts, Anahtar Sözcükler: Odontojenik tümörler, Odontojenik kistler, Immunohistochemistry İmmünohistokimya (Turk Patoloji Derg 2015, 31:104-110) Correspondence: Ayhan ÖZCAN Gülhane Askeri Tıp Akademisi, Patoloji Anabilim Dalı Received : 26.08.2014 Accepted : 11.10.2014 General Tevfik Sağlam Caddesi, 06018 Etlik, Ankara, TURKEY E-mail: [email protected] Phone: + 90 312 304 37 06 104 ÖZCAN A et al: Immunoprofiles of Odontogenic Lesions Turkish Journal of Pathology INTRODUCTION angiogenesis, tumor invasion, and metastasis (21). Loss of CD138 expression is associated with increased invasive Cystic ameloblastoma (CA), keratocystic odontogenic and metastatic potential in carcinomas (22). It has been tumor (KCOT), dentigerous cyst (DC), and radicular suggested that CD138 is essential for the maintenance cyst (RC) are the most commonly encountered cystic of epithelial morphology and control of cytoskeletal odontogenic lesions. Among cystic odontogenic lesions, organization and its expression has prognostic value in ameloblastoma and keratocystic odontogenic tumors clinical outcome of ameloblastomas and odontogenic cysts (KCOTs) are regarded as benign, but they can be locally (24). invasive with extensive bone destruction. CD38 is a transmembrane molecule and found on the Survivin, which is an inhibitor of apoptosis protein (IAP), surface of many immune cells including CD4+, CD8+, and is a bifunctional protein that suppresses apoptosis by B lymphocytes, in addition to natural killer cells. CD38 also inhibiting caspase activation while regulating cell division functions in cell adhesion, signal transduction and calcium- and promoting cell proliferation, differentiation, and dependent cell signaling pathways (25, 26). angiogenesis at the same time (1). Survivin is expressed in many various human malignancies including hepatocellular The differential diagnosis in odontogenic cystic lesions and carcinoma, colorectal cancer, lung cancer, pancreatic and the understanding of their pathogenesis are essential for their kidney cancers, and osteosarcoma (2-7). Survivin plays an accurate diagnosis and the determination of appropriate important role both in initiation and progression of these treatment modalities. Although there are several studies tumors (2-7). Over-expression of survivin is suggested related to role of these proteins in odontogenic lesions to be associated with aggressive behavior in KCOTs and in English literature (8, 9, 18, 24, 27-29), no comparative ameloblastomas (8, 9). and comprehensive study, in which the expression of these 2+ proteins or adhesion molecules in odontogenic cystic E-cadherin is the major Ca dependent cell adhesion lesions have been evaluated, to our knowledge. Therefore, molecule of epithelial cells and plays a role in morphogenesis we aim to evaluate the immunohistochemical expressions and the maintenance of the integrity of epithelial cells (10, of CD138 (syndecan-1), CD38, E-cadherin and survivin 11). E-cadherin expression is inversely proportional to in these cystic odontogenic lesions and investigate the the degree of differentiation in various cancers. Loss of potential implications of their expressions among these E-cadherin-mediated cell-cell adhesion is associated with lesions. the progression of many carcinomas including breast, bladder, gastric, squamous head and neck cancers (12-15). MATERIAL and METHODS Loss of E-cadherin expression in the epithelium of invasive A total of 20 cases consisting 5 radicular cysts (RCs), squamous cell carcinomas and squamous intraepithelial 5 dentigerous cysts (DCs), 5 keratocystic odontogenic lesions of the uterine cervix and skin reduces the density tumors (KCOTs) and 5 cystic ameloblastomas (CAs) of Langerhans cells, and thus compromises the capacity of were included in this study. For all cases, sections from dendritic cells to recognize tumor antigens (16-18). the selected blocks were stained against the antibodies for CD138 and CD38 have been widely used as plasma cells survivin (Neomarkers, Labvision, Ab-2, clone 4F7, 1/100 markers in hematopoetic malignancies (19, 20). CD138, dilution, avidin-biotin-peroxidase), E-cadherin (Dako, also known as syndecan 1, is a transmembrane heparin Clone NCH-38, 1/100 dilution, avidin-biotin-peroxidase), sulfate proteoglycan. CD138 (syndecan 1 is a highly CD138 (Cell Marqoue, clone B-A38, 1/100 dilution, avidin- expressed antigen in epithelial cells. However, expressions biotin-peroxidase), and CD38 (Novocastra, clone NCL- of other syndecans, syndecan 2 in mesothelial, endothelial, CD38-290, 1/100 dilution, avidin-biotin-peroxidase) on an neural and fibroblastic cells, syndecan 3 in neural cells, and automated device (Ventana, Benchmark XT). The staining syndecan 4 in epithelial and fibroblastic cells, are known intensity was graded and recorded semi-quantitatively as 0 not to be high in epithelial cells. CD138 (syndecan 1) is a (no staining), 1+ (weak), 2+ (moderate) and 3+ (strong). receptor for extracellular matrix proteins such as collagen, RESULTS fibronectin and thrombospondin, and participates in cell proliferation, cell migration, and cell interactions (19, 20). All staining scores were summarized in Table I. CD138 plays a role in the differentiation of B lymphocytes The features of survivin expression in the cystic odontogenic to plasma cells and is observed in non-neoplastic plasma lesions: All CAs (Figure 1 A,B) and KCOTs (Figure 1 C,D) cells, neoplastic plasma cells in multiple myeloma, and the showed diffuse and strong nuclear survivin expression in plasmacytic component in lymphoplasmacytic lymphoma all epithelial and stromal cells with some weak cytoplasmic (20). It is also expressed in many solid tumors including staining, as well. Epithelial staining in these cases was breast, colon, lung, prostate, and kidney cancers (20- strongest in basal cell layer. In contrast, weak cytoplasmic 23). It modulates cancer cell proliferation and apoptosis, and nuclear staining in all epithelial layers with basal cell Vol. 31, No. 2, 2015; Page 104-110 105 Turkish Journal of Pathology ÖZCAN A et al: Immunoprofiles
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