基質金屬蛋白酵素-9在犬隻良惡性乳腺腫瘤之表現

Abstract

母犬的乳腺腫瘤是小動物臨床上經常遇到的腫瘤病例之一。而乳腺腫瘤的病例中大約50 %是屬於惡性的腫瘤。因為腫瘤細胞的遠端轉移可造成器官的功能抑制甚而衰竭，此種臨床變化是犬隻最終造成死亡的主要原因。因此，設法利用當腫瘤細胞要轉移時，基質金屬蛋白酵素-9活性的表現會增加以降解細胞外基質，而利於腫瘤細胞穿過基底層的特性，作為犬乳腺腫瘤早期轉移的指標;進行探討其早期診斷之可行性評估。 腫瘤樣本來自中興大學獸醫教學醫院小動物外科的門診病例，經外科手術切除的乳腺腫瘤組織。以TNM system分析病例作為臨床分期，並配合組織病理學分類與偵測基質金屬蛋白酵素-9的活性表現;共同作為犬乳腺腫瘤預後判定。Zymography的結果顯示在已出現腫瘤轉移的病例中，腫瘤原發部位、區域淋巴結、轉移至肺臟的腫瘤組織在92 kDa處皆出現明顯的明膠溶解帶。我們發現在犬乳腺腫瘤中，惡性混合型腫瘤的基質金屬蛋白酵素-9的活性顯著高於其他組織病理學分類的腫瘤。若僅以組織病理學上的良惡性分類作為區分，則在惡性的腫瘤組織中基質金屬蛋白酵素-9的活性顯然高於良性腫瘤組織。基質金屬蛋白酵素-9的活性表現與犬乳腺腫瘤的轉移作用呈現高度正相關性。因此，本研究結果顯示，在犬乳腺腫瘤的診斷與治療流程中，例行偵測基質金屬蛋白酵素-9的活性，可作為輔助診斷早期轉移的指標，而使得犬隻在乳腺腫瘤之診察與治療計畫時可更為完整。

Mammary gland tumors in bitch are one of the most common neoplastic cases in small animal clinical practice. Approximately 50% of mammary gland tumor cases are malignant. The distant metastasis of tumor causes the inhibition of organ function or even failure, which was the major result in death. Therefore, the expression of matrix metalloproteinase-9 (MMP-9) activity would enhance to dissolve extracellular matrix (ECM) in the metastasis stage, in order for the character of tumor cells to get through basement membrane. MMP-9 could be an early indicator for the metastasis of the canine mammary gland tumors. The tumor samples were obtained from the cases of small animal surgery department in the Veterinary Teaching Hospital of Chung-Hsing University. We analyzed the clinical stages by TNM system and coordinated the classifications of histopathology, with the expression of MMP-9 activity as the prognostic factors in canine mammary gland tumors. In metastatic cases, zymography presented a clear band on 92kDa in the samples of primary tumor, regional lymph node, and the tumor tissue which metastated to the lung. We found that malignant mixed tumor had higher expression of MMP-9 activity than other histopathological classifications in canine mammary gland tumor. If we only distinguished benign and malignant from histopathology, the expression of MMP-9 activity was apparently higher in malignant samples than benign ones. There was a high relationship between the expression of MMP-9 and mammary gland tumor cells metastasis in dog. For this reason, we recommended to routine use the expression of MMP-9 activity as an early indicator for metastasis in the schedule of diagnosis and treatment of canine mammary gland tumor, in order to make the diagnosis and therapy more complete.