Expression of chemokine receptor 6 and chemokine receptor 7 in oral epithelial dysplasia and squamous cell carcinoma

背景： 化學趨化因子接受器6及7 (CCR6及CCR7) 在人類不同的癌症中被發現有過度表現的現象 , 而且和腫瘤的大小、淋巴結的轉移、臨床的分期、腫瘤的侵犯 , 或病人的預後等有統計上有意義的相關。法：本研究利用免疫組織化學染色的方法 , 探討CCR6及CCR7於123例口腔鱗狀細胞癌 (OSCC)、105例口腔上皮變異 (OED; 35例輕度、37例中度、33例重度) , 和25例正常口腔黏膜 (NOM) 之表現。我們計算在口腔鱗狀細胞癌、口腔上皮變異與正常口腔黏膜中的細胞質與細胞膜CCR6或CCR7標記指數 (labeling indices , LIs) , 並比較各組間的差異。我們同時利用統計方法來分析細胞質與細胞膜CCR6或CCR7標記指數與口腔鱗狀細胞癌病人的臨床病理參數與存活率的相關性。果：在較高的CCR6 平均標記指數與男性病患 (P=0.042) 或淋巴結轉移 (P=0.027) 之間有著統計上顯著的差異。細胞質與細胞膜CCR7平均標記指數 , 從NOM至OED至OSCC有隨著惡性程度的增加而呈現統計學上有意義增加的情形(P=0.000) , 而且在較大腫瘤 (T3及T4)、淋巴結轉移 (N1、N2及N3) 及轉移淋巴結之淋巴結外散佈、較高的臨床分期 (臨床分期4 )之病患具有較高的表現量。論： CCR7在細胞質及細胞膜的表現從NOM至OED至OSCC有顯著的增加 , 而且和Ｔ分期、Ｎ分期及轉移淋巴結之淋巴結外散佈、及臨床分期有相關性。 我們的結果顯示CCR7的表現可以預測台灣OSCC的進展。Background: Overexpression of chemokine receptors 6 and 7 (CCR6 and CCR7) have been demonstrated in a variety of human cancers and found to be significantly associated with the tumor size, lymph node metastasis, clinical stage, tumor invasion, or prognosis of these cancers.ethods: In this study, we examined the expression of CCR6 and CCR7 proteins in 123 specimens of oral squamous cell carcinoma (OSCC), 105 specimens of oral epithelial dysplasia (OED; 35 mild, 37 moderate, and 33 severe cases), and 25 specimens of normal oral mucosa (NOM) by immunohistochemistry. The cytoplasmic and membranous CCR6 or CCR7 labeling indices (LIs) in OSCC, OED, and NOM samples were calculated and compared between groups. The correlation between the cytoplasmic and membranous CCR6 or CCR7 LIs in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed statistically.esults: There was a significant correlation between the higher mean CCR6 LI and OSCCs in male patients (P = 0.042) or with lymph node metastasis (P = 0.027). The mean CCR7 LIs increased significantly from NOM through OED to OSCC samples (P = 0.000). There is a significant correlation between the higher mean CCR7 LI and OSCCs with larger tumor size (P = 0.001), regional lymph node metastasis (P = 0.041), more advanced clinical stage (P = 0.017), and extranodal spread (P = 0.007).onclusion: The expression of CCR7 significantly increases form NOM through OED to OSCC samples, and is related to T status, N status, clinical staging, and extranodal spread of OSCCs. The CCR7 LI in OSCC samples can predict the progression of OSCC in Taiwan.中文摘要…………………………………………………………………7bstract………………………………………………………………8ntroduction……………………………………………………………9urposes of this study………………………………………………11iterature Review……………………………………………………12art 1: Introduction of oral squamous cell carcinoma……………………12i)Epidemiology in the world………………………………………12ii)Epidemiology in Taiwan………………………………………13iii)Etiology…………………………………………………………13iv)Clinical features………………………………………………16v)Histologic features………………………………………………18vi)Staging and grading……………………………………………19art 2: Prognostic factors of oral squamous cell carcinoma……………20i)Clinical factors…………………………………………………20ii)Histopathological factors……………………………………21iii)Molecular factors………………………………………………26Part 3: Chemokine and Chemokine receptor……………………28i)Introduction……………………………………………………28ii)Function……………………………………………………………28iii)Structural characteristics…………………………………29iv)Type…………………………………………………………………30Part 4: CC chemokine receptor 6…………………………………30i)Structure of protein and gene location……………………....30ii)Function of CCR6…………………………………………………31iii)Regulation of CCR6 expression……………………………...31iv)CCR6 expression in normal cells ……………………………32v)CCR6 expression in tumor cell lines…………………………33vi)CCR6 expression in cancers……………………………………34vii)CCR6 expression in OSCC……………………………………36art 5: CC chemokine receptor 7………………………………….36i)Structure of protein and gene location……………………36ii)Function of CCR7…………………………………………………37iii)Regulation of CCR7 expression……………………………38iv)CCR7 expression in normal cells ……………………………39v)CCR7 expression in tumor cell lines…………………………40vi)CCR7 expression in cancers……………………………………40vii)CCR7 expression in OSCC………………………………………43aterials and Methods………………………………………………44art 1: Patients and specimens………………………………………………44art 2: Immunohistochemical staining for CCR6 and CCR7………………………45art 3: Statistical analysis……………………………………47esults…………………………………………………………………48art 1: The mean CCR6 or CCR7 LIs for NOM, OED, and OSCC samples…………………………………………………………………48 Part 2: Correlation between the mean CCR6 or CCR7 LIs in OSCCs and clinicopathological parameters of OSCC patients…………………………49 Part 3: Correlation between the mean CCR6 or CCR7 LIs in OSCCs and oral habits of OSCC patients………………………50 Part 4: Correlation between CCR6 or CCR7 LIs in OSCCs and survival of OSCC Patients…………………………………50iscussion………………………………………………………………51onclusion………………………………………………………………56eference………………………………………………………………5