轉移相關蛋白1於口腔癌前病變及口腔鱗狀細胞癌之表現

Abstract

背景：轉移相關蛋白１(MTA1)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。 方法：本研究利用免疫組織化學染色的方法，探討MTA1於74例口腔鱗狀細胞癌（OSCC），100例口腔上皮變異（ED；33例輕度，44例中度，23例重度上皮變異），和21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核MTA1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核MTA1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。 結果：在正常口腔黏膜、口腔上皮變異、及口腔鱗狀細胞癌中，細胞質MTA1平均標記指數皆大於95%，且和口腔鱗狀細胞癌病人的臨床病理參數，無統計學上有意義之相關。細胞核MTA1平均標記指數，從NOM之73±13%，至輕度ED之71±16%，至中度ED之60±22%，至重度ED之46±25%，至OSCC之30±30%，有隨著惡性程度的增加而呈現統計學上有意義降低的情形（P=0.000)。統計分析的結果也顯示，細胞核MTA1平均標記指數在OSCCs中之較低表現和OSCCs發生在頰黏膜與舌、較大的OSCC腫瘤、有局部淋巴結的轉移與較高的臨床分期，有統計學上有意義之相關。 結論：我們的結果顯示，MTA1廣泛地表現在正常的、變異的與惡性的口腔上皮細胞之細胞質中。而MTA1在細胞核的表現從NOM至ED至OSCC有顯著的降低，且和OSCC病人的腫瘤大小、淋巴結轉移以及臨床分期呈現負相關。因此細胞核MTA1標記指數可預測台灣OSCC的進展。

Background: Overexpression of metastasis-associated protein 1 (MTA1) has 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. Methods: In this study, we examined the expression of MTA1 protein in 74 specimens of oral squamous cell carcinoma (OSCC), 100 specimens of oral epithelial dysplasia (ED; 33 mild, 44 moderate, and 23 severe ED cases), and 21 specimens of normal oral mucosa (NOM) by immunohistochemistry. The cytoplasmic and nuclear MTA1 labeling indices (LIs) in OSCC, ED, and NOM samples were calculated and compared between groups. The correlation between the cytoplasmic or nuclear MTA1 LI in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed statistically. Results: The mean cytoplasmic MTA1 LIs were all over 95% for NOM, ED and OSCC samples. There was no significant association of the cytoplasmic MTA1 LI with any of the clinicopathological parameters of OSCC patients. The mean nuclear MTA1 LIs decreased significantly from NOM (73±13%) through mild ED (71±16%), moderate ED (60±22%), and severe ED (46±25%) to OSCC samples (30±30%, P=0.000). A significant correlation was found between the lower mean nuclear MTA1 LIs and OSCCs located at the buccal mucosa and tongue (P=0.001), with larger tumor sizes (T3 and T4, P=0.020), with regional lymph node metastases (N1, N2 and N3, P=0.024), or with more advanced clinical stages (stages 3 and 4, P=0.045). Conclusion: Our results suggest that the MTA1 is universally expressed in the cytoplasm of normal, dysplastic and malignant oral epithelial cells. The nuclear expression of MTA1 significantly reduced from NOM through ED to OSCC samples, and is inversely related to T status, N status, and clinical staging of OSCCs. Therefore, the nuclear MTA1 LI can be used to predict the progression of OSCCs in Taiwan.