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標題: 犬惡性末梢神經鞘瘤PLOD2表現與組織病理學特徵的相關
Association between PLOD2 expression and histopathological characteristics in canine malignant peripheral nerve sheath tumors
作者: 劉佑安
You-An Liu
關鍵字: 膠原基質;細胞外基質;惡性末梢神經鞘瘤;PLOD2;腫瘤微環境;collagen;extracellular matrix (ECM);malignant peripheral nerve sheath tumor (MPNST);PLOD2;tumor microenvironment (TME)
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Procollagenlysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2)為穩定膠原纖維結構的重要酵素。腫瘤微環境對於許多腫瘤的進展和侵犯行為有關,而PLOD2則藉由調節細胞外基質的組成影響腫瘤微環境。惡性末梢神經鞘瘤是犬最常見的軟組織肉瘤,雖然相較於其它軟組織肉瘤而言具有較良性的生物行為,仍有少部分惡性末梢神經鞘瘤發生局部復發或遠端轉移。本實驗目的為評估PLOD2在惡性末梢神經鞘瘤的表現與其在組織病理學特徵和預後之關聯性。本研究包括取自105隻犬的共110個惡性末梢神經鞘瘤,藉由西方墨點法確認PLOD2抗體與犬的組織之特異結合後,再以免疫組織化學染色分析PLOD2抗體在腫瘤組織的表現;腫瘤細胞外基質則藉由Masson's trichrome與Alcian blue pH2.5特殊染色分別突顯膠原與黏液基質的表現。結果發現共78.2% (86/110)的腫瘤樣本具有PLOD2表現。單變因分析顯示PLOD2的表現與臨床分期、腫瘤內的膠原基質含量、腫瘤分化程度、壞死灶多寡和組織分級顯著相關(P<0.05);多變因分析則發現PLOD2與腫瘤的侵犯生長(P=0.046)與較多膠原基質含量(P=0.011)成正相關。在存活分析方面,PLOD2的表現僅於單變因分析結果發現為影響整體存活時間的負面預後因子(P=0.028),其它不良的預後因子包括有絲分裂數目高(P=0.048)、遠端轉移(P=0.004)、腫瘤局部復發(P=0.004)和未接受手術治療(P=0.001)皆在多變因結果具統計顯著性。總括而言,犬惡性末梢神經鞘瘤的腫瘤細胞之PLOD2表現與腫瘤內的膠原基質含量和侵犯的生長模式具正相關性,但無法作為單一獨立的預後因子。

Procollagenlysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is an enzyme that modify the extracellular matrix (ECM) in tumor microenviroment (TME) through stabilizing the cross-links of collagen. This alteration in ECM was thought to play a role in tumor progression and aggressive behaviors in many tumors. Malignant peripheral nerve sheath tumor (MPNST) is the most common soft tissue sarcoma (STS) in dogs. Since the universal benign biological behavior compare with other STSs, some MPNST still appear with aggressive manners such as local recurrence and distant metastasis. The aim of this study was to evaluate the association of PLOD2 expression, histopathological characteristics and prognostic factors in canine MPNSTs. The total of 110 MPNSTs from 105 dogs were enrolled. The specific binding of PLOD2 antibody was identified by Western blotting. While PLOD2 was analyzed immunohistochemically, Masson's Trichrome and Alcian blue pH 2.5 were used to highlight collagenous and mucinous stroma, respectively. The immunoreactivity of PLOD2 was detected in 78.2% (86/110) of tumors. In univariate analysis, the immunoreactivity of PLOD2 was significantly (P<0.05) correlated with clinical stage, collagenous stroma in tumor parenchyma, degree of differentiation, amount of necrosis, and histological grade. In the multivariate model, presence of invasive growth pattern of tumor cells (P=0.046) and greater amount of collagenous stroma (P=0.011) were significantly associated with PLOD2 expression. The stronger immunoreactivity of PLOD2 was correlated to shorter overall survival time in univariate analysis (P=0.028) but not in multivariate model. Other poor prognostic factors in multivariate model include high mitotic figures (P=0.048), presence with distant metastasis (P=0.004) and tumor local recurrence (P=0.004), and absence of surgical management (P=0.001). In conclusion, this study revealed the positive correlation of PLOD2 immunoreactivity with the amount of collagenous stroma and invasive growth pattern of tumor cells as well; however, PLOD2 might not be used as a sole prognostic factor for canine MPNSTs.
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