Samantaray S, Sharma R, Chattopadhyaya T K, Gupta S Datta, Ralhan R
Department of Biochemistry, All India Institute of Medical Sciences, 110029 New Delhi, Ansari Nagar, India.
J Cancer Res Clin Oncol. 2004 Jan;130(1):37-44. doi: 10.1007/s00432-003-0500-4. Epub 2003 Oct 16.
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.
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.
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.
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.
已知基质金属蛋白酶（MMPs）在肿瘤侵袭和转移过程中的细胞外基质重塑中起重要作用。然而，它们在侵袭前病变和早期食管癌中的作用却知之甚少。
对手术切除的食管鳞状细胞癌（ESCC，58例）及配对的远端正常食管组织（44例）的石蜡包埋切片进行基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）表达的免疫组织化学分析，并与临床病理参数相关联。
在58例ESCC中，分别有39例（67%）和32例（55%）观察到MMP-2和MMP-9蛋白的过表达，分别定位于肿瘤细胞胞质和基质成分中。对44例配对的远端正常食管组织切片进行苏木精和伊红染色的组织学评估显示，26例由正常上皮组成，而15例组织显示发育异常证据，3例组织显示增生。有趣的是，这15例发育异常组织中分别有12例（80%）和13例（87%）显示MMP-2和MMP-9蛋白免疫染色阳性。在26例组织学正常的配对食管组织中，分别有10例（38%）和6例（23%）观察到低水平的MMP-2和MMP-9。与低分化肿瘤相比，在高分化和中分化SCC中观察到更高的MMP-2免疫阳性。随着食管SCC的逐渐去分化，MMP-2的表达显著降低（P = 0.03）。发育异常以及SCC中MMP-2和MMP-9的过表达表明这些改变发生在食管肿瘤发生的早期阶段。
与正常食管组织相比，ESCC中MMP-2和MMP-9蛋白水平升高表明它们与食管肿瘤发生有关。在本文分析的大多数发育异常组织中观察到这些MMPs水平升高，表明这些改变可能是食管肿瘤发生的早期事件。有必要进行深入研究以确定它们在食管癌发生和发展中的作用。
