SIBLING 蛋白群及其受器於造釉細胞瘤與齒源性囊腫之表現

造釉細胞瘤為發生於顎骨之最常見良性齒源性腫瘤，並且以其組織學型態類似發育中牙齒之釉器官而命名。一般臆測，此一腫瘤可能發源於齒源上皮，但其確切來源及腫瘤發生機制卻仍渾沌未明。造釉細胞瘤雖然於組織型態上定義為良性腫瘤，但臨床病徵卻以局部侵蝕破壞顎骨組織而廣為人知，並以此點特異於其他齒源性病變。造成此一局部組織侵蝕特性的生物機轉不但仍屬未知，探求與此侵蝕性相關之生物標記，雖然持續進行著，但迄今仍無所獲。針對這些謎題，吾人乃設計進行本實驗，以免疫組織化學染色法分析 osteopontin，bone sialoprotein， integrinㄇ，CD44s 及 CD44v6 於造釉細胞瘤之表現。本實驗造釉細胞瘤的樣本數為三十一例。本實驗亦收集二十例齒源性角化囊腫，八例含齒囊腫，十例根尖囊腫，以及九枚發育中之牙胚以為比較。依組織學分類，本實驗收集之造釉細胞瘤計分為：濾胞型 (6 例，19.4%)；叢狀型 (11例，30.5%)；棘狀型 (4例， 12.9%)；纖維緻密型 (1例，3.2%)；單室型 (內襯型: 1例，3.2%；腔內型: 2例，6.5%；壁型: 5例，16.1%) 以及週邊型 (1例，3.2%)。為觀察比較基質蛋白及其受器於造釉細胞瘤內之分布，腫瘤上皮細胞依型態進一步區分為似造釉細胞之基底細胞以及似星型網狀細胞之基底上細胞，以利免疫組織化學染色後之定位及統計分析。齒源性囊腫之上皮襯裡細胞，則區分為基底細胞､基底上細胞､及角化細胞以利觀察。所得之結果如下：(1) 本實驗中，各類受測蛋白質於不同類別造釉細胞瘤之表現模式無明顯差異。(2) osteopontin在造釉細胞瘤與齒源性角化囊腫之表現率，於統計上有顯著性差異 (87.1% vs. 20%, 費雪正確機率檢定，p<0.001)。(3) osteopontin在造釉細胞瘤與齒源性囊腫之基質中的表現亦有顯著性差異。(4) bone sialoprotein 之表現率不論是在造釉細胞瘤或齒源性囊腫普遍偏低或未表現 (造釉細胞瘤，9.67%；齒源性角化囊腫，0%；含齒囊腫，0%；根尖囊腫，0%)。(5) integrinㄇ於造釉細胞瘤之表現率亦顯著地高於齒源性角化囊腫 (47.6% vs. 0%，費雪正確機率檢定，p<0.001)。另一方面，幾乎本實驗中所有之含齒囊腫及根尖囊腫內襯上皮皆表現integrinㄇ之特殊染色。(6) 造釉細胞瘤中，CD44s 於似造釉細胞及似星型網狀細胞之表現具統計上顯著差異 (57.1% vs. 100%，費雪正確機率檢定，p=0.001)，而CD44v6 則無此現象 (85.7% vs. 90.5%，費雪正確機率檢定，p=1.000)。另一方面，比較CD44s與CD44v6在似造釉細胞之表現，則CD44v6遠高於CD44s (85.7% vs. 57.1%);於似星型網狀細胞中，CD44s 與 CD44v6 之表現則相類似 (100% vs. 90.5%)。(7)齒源性角化囊腫內襯上皮之基底細胞與基底上細胞均表現CD44s 與 CD44v6，但內襯上皮最表層之不全角化細胞則不表現此二種蛋白。(8) 造釉細胞瘤之腫瘤上皮細胞，不論在組織學或免疫化學染色觀察下，均與發育中牙胚有正向關聯。這些結果顯示造釉細胞瘤之組織來源類似造牙器官之早期原始上皮，再則顯示本實驗所探查之基質蛋白與其受器間的相互作用，可能與造釉細胞瘤對骨組織之特異侵蝕性有關。

關鍵字

SIBLING 蛋白群；齒源性囊腫；造釉細胞瘤

並列摘要

An immunohistochemical study was conducted to investigate the presence of osteopontin (OPN), bone sialoprotein (BSP), integrinㄇ, CD44s and CD44v6 in 31 ameloblastoma. Twenty odontogenic keratocysts (OKC), 8 dentigerous cysts and 10 radicular cysts as well as 9 developing tooth germs are enrolled for parallel studies. Histologically, we recognized each of the ameloblastomas in the following subtypes: follicular (6 cases, 19.4%), plexiform, (11 cases, 30.5%), acanthomatous (4 cases, 12.9%), desmoplastic (1 case, 3.2%), unicystic (luminal, 1 case, 3.2%; intraluminal, 2 cases, 6.5%; mural, 5 cases, 16.1%) and peripheral (1 case, 3.2%). Neoplastic epithelia were divided into ameloblast-like basal cells and stellate reticulum-like suprabasal cells to compare the immunohistochemical locolization. The results made were as following: (1) there was no difference in expression patterns of the proteins we studied in present study between the subtypes of the ameloblastomas. (2) OPN positivity in ameloblastomas was significantly higher than that in the OKC in the present study after Fisher’s exact test (87.1% vs. 20%, p<0.001). (3) significant difference in OPN expression was noted between ECM of ameloblastomas and odontogenic cysts. (4) BSP was generally negative in odontogenic lesions enrolled. (5) Integrinㄇ reactivity in ameloblastmas was 47.6% that was significantly higher than that in OKC, the latter did not demonstrate any reaction to the protein (p<0.001). Nearly all of the dentigerous cysts and radicular cysts showed the staining of the adhesion protein. (6) There is a statistic differnce in CD44s expression between ameloblast-like cells and stellate reticulum-like cells of ameloblastomas (57.1% vs. 100%, p=0.001), whereas CD44v6 tells a different story (85.7% vs. 90.5%, p=1.000). With regard to the immunoreactivity of CD44s and CD44v6 in ameloblast-like cells, the latter was higher than that of the former (85.7% vs. 57.1%). A nearly equal reactivity to both antibodies exsisted in stellate reticulum-like cells of the tumors. (7) Both CD44s and CD44v6 antibodies reacted to the whole thickness of cyst lining epithelia of OKC except the parakeratinized cells of cyst lining. (8) The neoplastic epithelia of the ameloblastomas revealed a clear phenotypic and immunohistochemical reactive relationship to the tooth germs in different developing ages. These results suggest that the histogenesis of ameloblastoma is from an early primitive epithelium of dental organ. They may also imply to the distinct aggressive behavior of ameloblastoma from other lesions.

並列關鍵字

osteopontin ； SIBLING proteins ； CD44s ； odontogenic keratocyst ； radicular cyst ； bone sialoprotein ； dentigerous cyst ； integrinㄇ； CD44v6 ； ameloblastoma ； OPN ； BSP

參考文獻

Ackermann GL. Altini M. Shear M. The unicystic ameloblastoma: a clinicopathological study of 57 cases Journal of Oral Pathology. 17(9-10):541-6, 1988 Nov.

Agrawal D. Chen T. Irby R. Quackenbush J. Chambers AF. Szabo M. Cantor A. Coppola D. Yeatman TJ. Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling Journal of the National Cancer Institute. 94(7):513-21, 2002 Apr 3

Andreasen P. Kioller L. Christensen L. Duffy M. The urokinase type plasminogen activator system in cancer metastasis: a review. International Journal of Cancer 72: 1-22, 1997

Ashkar S. Weber GF. Panoutsakopoulou V. Sanchirico ME. Jansson M. Zawaideh S. Rittling SR. Denhardt DT. Glimcher MJ. Cantor H. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity Science. 287(5454):860-4, 2000 Feb 4

Bautista DS. Saad Z. Chambers AF. Tonkin KS. O'Malley FP. Singhal H. Tokmakejian S. Bramwell V. Harris JF. Quantification of osteopontin in human plasma with an ELISA: basal levels in pre- and postmenopausal women Clinical Biochemistry. 29(3):231-9, 1996 Jun

國際替代計量

SIBLING 蛋白群及其受器於造釉細胞瘤與齒源性囊腫之表現

全文下載

主題瀏覽