Expression of matrilysin (matrix metalloproteinase-7) in primary cutaneous and metastatic melanoma

Expression of matrilysin (matrix metalloproteinase-7) in primary cutaneous and metastatic melanoma
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DOI:
10.1111/j.1365-2133.2006.07678.x
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发表时间:
2007-04-01
影响因子:
10.3
通讯作者:
Soma, Y.
Soma, Y.
中科院分区:
医学1区
文献类型:
--
作者:
Kawasaki, K.;Kawakami, T.;Soma, Y.

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基质溶素(MMP-7)是基质金属蛋白酶(MMP)蛋白家族的一员,在多种类型的恶性肿瘤中表达。此前还没有关于基质溶素表达与黑色素瘤之间关系的研究。目的评价基质溶素蛋白在人皮肤黑色素瘤、转移性黑色素瘤、获得性普通黑色素细胞痣和Spitz痣中的表达,并结合临床病理因素进行校正。方法对18例原发性黑色素瘤、15例转移性黑色素瘤、10例普通黑色素细胞痣和5例痣样进行免疫组化(IHC)回顾性分析。免疫印迹法在黑色素瘤组织提取物中发现了原基质溶素和活性基质溶素。原位杂交证实黑色素瘤细胞选择性表达基质溶素mRNA。结果33例黑色素瘤样本中29例(87.9%)母体溶素阳性,其中18例原发性皮肤黑色素瘤中14例(77.8%),15例转移性黑色素瘤中15例(100%)。而在普通痣和Spitz痣中均不表达matrilysin。原发性黑色素瘤的基质溶素IHC染色评分与转移、肿瘤厚度和TNM分期相关(P分别为0.001、0.025和0.021)。黑色素瘤标本中,母体素阳性病例的5年总生存率为26.3%,母体素阴性病例的5年总生存率为100%。结论在原发性黑色素瘤和转移性黑色素瘤中均发现基质溶素的表达。我们进一步证明基质溶素IHC染色评分与原发性黑色素瘤病变和转移灶的浸润深度有关。我们的观察表明,基质溶素可能与黑色素瘤的进展有关,并可能增强黑色素瘤肿瘤细胞的侵袭。因此,基质溶素可能作为预测黑色素瘤临床行为的预后指标具有潜在的价值。
Background Matrilysin (MMP-7), a member of the matrix metalloproteinase (MMP) family of proteins, is expressed in various types of malignant tumours. There have been no previous studies of the correlation between matrilysin expression and melanoma.Objectives Protein expression of matrilysin was evaluated in human cutaneous melanomas, metastatic melanomas, acquired common melanocytic naevi and Spitz naevi, and the data were corrected with the clinicopathological factors.Methods We retrospectively investigated 18 primary melanomas, 15 metastatic melanomas, 10 common melanocytic naevi and five Spitz naevi samples at our clinic using immunohistochemistry (IHC). Both promatrilysin and active matrilysin were found in the melanoma tissue extracts by Western immunoblotting. In situ hybridization demonstrated that melanoma cells selectively express matrilysin mRNA.Results Of the melanoma samples, 29 of 33 (87.9%) were positive for matrilysin, including 14 of 18 (77.8%) primary cutaneous melanomas and 15 of 15 (100%) metastatic melanomas. In contrast, matrilysin was not expressed in common naevi or Spitz naevi. The matrilysin IHC staining score in primary melanomas was associated with the presence of metastases, tumour thickness and TNM staging (P = 0.001, 0.025 and 0.021, respectively). The 5-year overall survival was 26.3% for matrilysin-positive cases and 100% for matrilysin-negative cases among melanoma specimen.Conclusions We found matrilysin expression in primary melanomas and in metastatic melanomas. We further demonstrated that the matrilysin IHC staining score was associated with invasive depth of primary melanoma lesions and metastases. Our observations indicate that matrilysin may be associated with melanoma progression, and may enhance melanoma tumour cell invasion. Therefore, matrilysin may be potentially valuable as a prognostic indicator to predict the clinical behaviour of melanoma.