癌症的治療中重要的一步就是『早期診斷，早期治療』，目前口腔癌的診斷主要以切片檢查為主，對於顯而易見位置獨立且體積較小的疑似病灶作切除及病理切片(excisional biopsy)檢查，對體積較大的病灶則取多個代表部位進行切片(incisionalbiopsy) ，於顯微鏡下觀察區分出病灶之良惡性及分化程度，然而口腔黏膜區域性癌化(field cancerization) 的過程所造成的瀰漫性癌前變化，往往導致其口腔內並無單一明顯徑渭分明的病灶出現，以至於進行偵測篩檢預防時反而成為檢查最困難的對象。因此尋找一個專一性及敏感性高的早期診斷方式可以及早確立治療方式，避免因多次切片檢查延誤治療時間，進而提高口腔癌存活率，在口腔癌的治療上顯的格外重要。除此之外，目前對於病患預後及術後是否接受輔助治療主要的依據是臨床及病理期別，但是其是否會轉移並無法預測，而在統計上大約會有兩成患者會有潛藏轉移，因而若是可以有分子標記來辨識出哪類的口腔癌具有高度的轉移可能性則是相對重要，如此臨床上便可做為病患預後及術後是否接受輔助治療之參考。Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) 最早被發現在胰臟癌具高量表現，IMP3可以結合在insulin-like growth factor II (IGF2) leader 3 mRNA 的5' UTR
而抑制發育晚期IGF2的轉錄(translation)。目前已知其參與了胚胎的形成及部分腫瘤的癌化，在多數的癌症中有高量表現，包括胰臟癌、肺癌、胃癌、大腸癌、子宮頸內腺癌、子宮內膜癌及食道癌，而其鄰近良性組織卻不會有IMP3的表現。而IMP3在口腔癌的表現如何目前還未有相關研究報告，因此探討IMP3的表現與口腔癌前病變、口腔癌轉移及預後的關係，將可提供口腔癌早期分子診斷與治療之參考。本研究探討IMP3的表現與口腔癌前病變、口腔癌轉移及預後之關係，分別取樣口腔癌前病變及口腔癌之手術患者樣本，分別以逆轉錄定量即時聚合鏈反應和免疫組織化學染色法定量此基因在樣本中其mRNA和蛋白質的表現，再進行臨床資料交叉比對，以期驗證IMP3與口腔癌及口腔癌前病變之相關性，並在日後臨床上可做為一有效之診斷、預測轉移及預後之因子。本研究發現經逆轉錄定量即時聚合鏈反應分析口腔癌及口腔癌前病變組織相對正常組織之IMP3表現量，口腔癌明顯比口腔癌前病變有較高之表現量(39.1倍:1.4倍)，經免疫組織化學染色法發現，口腔癌
亦明顯比口腔癌前病變有較高之表現量(p=0.002) ，進一步分析IMP3與組織病理因子之相關性，統計顯示兩者並無直接相關。本研究顯示藉由IMP3表現量的偵測可作為輔助口腔癌診斷之分子標記，然而是否可作為口腔癌預後之因子仍須更多之病患標本加以印證。

One of the most important cancer therapies is early diagnosis and early treatment. The diagnosis of oral cancer based on histological examination is usually sraight forward,substantial lesional/tumoral tissue is present in the biopsy specimens, but can be very difficult if there are only a few malignant tissues. The extensive oral precancerous change due to field cancerization leads to no distinct lesional boundary in the oral cavity, so it results in difficulty of early diagnosis. Therefore, it is so important to search for a sensitive and specific biomarker for early diagnosis can ensure the strategy of treatment, then avoiding multiple biopsies resulting in delay of treatment. Besides, prediction of prognosis
and selection of patients for postoperative adjuvant treatment is done mainly by pathological and clinical staging currently. However, because of substantial differences in the biological behavior of oral cancers classified in the same stage, the metastatic potential
of localized tumors is difficult to predict. About 20% of patients with localized tumors develop metastasis. Therefore, biomarkers that can accurately distinguish localized tumors with a high probability of metastasis from those that will remain indolent are needed. With such biomarker, physicians can predict the patient’s prognosis and effectively target the individuals who would benefit most from adjuvant treatment. Insulin-like growth factor-II
mRNA binding protein 3 (IMP3) is a newly identified oncofetal mRNA- binding protein that binds 5' UTR of the insulin-like growth factor II leader 3 mRNA and may repress
translation of insulin-like growth factor II during late development. IMP3 is expressed in many cells of the developing fetus. In contrast, it is not expressed in most adult tissue except in the gonads. However, IMP3 is expressed in a number of cancers including pancreas, lung, stomach, colon cancers, endocervical adenocarcinoma, endometrial serous carcinoma, soft tissue sarcoma, and esophageal adenocarcinoma but not in adjacent benign
tissues. However, whether IMP3 can serve as a prognostic biomarker to predict metastasis and prognosis of oral squamous cell carcinoma has not been clarified. The goal of this study is to establish the expression pattern and diagnostic value of IMP3 in oral squamous cell carcinoma and high-risk precancerous tissue and to determine whether IMP3 can serve as an early diagnostic and prognostic biomarker. Hence, the level of IMP3 expression in oral precancerous lesions and oral cancers from Department of Oral & Maxillofacial Surgery, Chi-Mei Medical Center by IHC and RT-qPCR assays were examined to accomplish this goal. The results from this study validate if a powerful diagnostic assay and prediction of metastasis and prognosis, and design new therapeutic approaches in the
future. In this study, the relative IMP3 expression in cases of oral squamous cell carcinoma tissues was higher (average 39.1-fold change) than the normal oral tissue versus in cases of precancerous tissue (average 1.4-fold change) by RT-qPCR. The IMP3 expression between precancerous and oral squamous cell carcinoma is significant difference statistically (P=0.002) by IHC. The detection of IMP3 expression levels can be used as a molecular marker to assist in the diagnosis of oral squamous cell carcinoma. However, it is not clear
whether IMP3 can be used to predict metastasis and prognosis in oral squamous cell carcinoma after correlating the histolopathologic parameter from this study.

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