Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma.
Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma.
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DOI：
10.1007/s00432-003-0500-4
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发表时间：
2004-01-01
影响因子：
3.6
通讯作者：
Ralhan, R
中科院分区：
文献类型：
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作者：
Samantaray, S;Sharma, R;Ralhan, R
目的.基质金属蛋白酶（MMPs）在肿瘤侵袭和转移过程中细胞外基质重塑中起重要作用。然而，很少有人知道他们的作用，在浸润前病变和早期食管癌。法应用免疫组织化学方法检测58例食管鳞癌（ESCC）和44例远端正常食管组织中基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的表达，并与临床病理参数进行相关性分析。结果. MMP-2和MMP-9蛋白在58例食管鳞癌中分别有39例（67%）和32例（55%）过度表达，分别位于肿瘤细胞胞浆和间质成分。苏木精和伊红染色的44个匹配的远端正常食管组织切片的组织学评价显示，26个由正常上皮组成，而15个组织显示发育异常的证据，3个组织显示增生。有趣的是，12（80%）和13（87%），这15个发育不良显示MMP-2和MMP-9蛋白的免疫染色，分别。MMP-2和MMP-9在26例匹配的组织学正常食管组织中分别有10例（38%）和6例（23%）呈低水平表达。MMP-2在高、中分化SCC中的表达明显高于低分化SCC。MMP-2的表达随着食管鳞癌去分化程度的加深而明显降低（P =0.03）。MMP-2和MMP-9在不典型增生和SCC中的过表达表明这些改变发生在食管肿瘤发生的早期阶段。结论MMP-2和MMP-9蛋白在食管鳞癌中的表达水平高于正常食管组织，提示其与食管肿瘤的发生有关。在本文分析的大多数发育不良中观察到这些MMP的水平增加，表明这些改变可能是食管肿瘤发生的早期事件。深入研究是必要的，以确定其在食管癌的发展和进展中的作用。
Purpose. Matrix metalloproteinases (MMPs) are known to play an important role in extracellular matrix remodeling during the process of tumor invasion and metastasis. However, little is known about their role in preinvasive lesions and early esophageal carcinomas. Method. Immunohistochemical analysis of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression was carried out in paraffin-embedded sections of surgically resected esophageal squamous cell carcinoma (ESCC) (58 cases) and paired distal normal esophageal tissues (44 cases) and correlated with clinicopathological parameters. Result. Overexpression of MMP-2 and MMP-9 proteins was observed in 39 (67%) and 32 (55%) of the 58 ESCCs, respectively localized in tumor cell cytoplasm and stromal elements. Histological evaluation of hematoxylin- and eosin-stained 44 matched distal normal esophageal tissue sections revealed that 26 comprised of normal epithelium, while 15 tissues showed evidence of dysplasia and three tissues showed hyperplasia. Interestingly, 12 (80%) and 13 (87%) of these 15 dysplasias showed immunostaining for MMP-2 and MMP-9 proteins, respectively. Low levels of MMP-2 and MMP-9 were observed in 10 (38%) and 6 (23%) of 26 matched histologically normal esophageal tissues, respectively. Higher MMP-2 immunopositivity was observed in well and moderately differentiated SCCs in comparison with poorly differentiated tumors. The expression of MMP-2 was significantly reduced with the progressive de-differentiation of esophageal SCCs (P =0.03). Overexpression of MMP-2 and MMP-9 in dysplasia as well as SCC suggests that these alterations occur in early stages of esophageal tumorigenesis. Conclusion. Increased levels of MMP-2 and MMP-9 proteins in ESCCs as compared to normal esophageal tissues suggest their association with esophageal tumorigenesis. Increased levels of these MMPs are observed in majority of dysplasias analyzed herein, indicating that these alterations may be early events in esophageal tumorigenesis. In-depth studies are warranted to determine their role in development and progression of esophageal cancer.