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Elevated nuclear maspin expression is associated with microsatellite instability and high tumour grade in colorectal cancer
Author(s) -
Bettstetter Marcus,
Woenckhaus Matthias,
Wild Peter J,
Rümmele Petra,
Blaszyk Hagen,
Hartmann Arndt,
Hofstädter Ferdinand,
Dietmaier Wolfgang
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1732
Subject(s) - maspin , microsatellite instability , colorectal cancer , cancer research , metastasis , immunohistochemistry , cancer , dna methylation , biology , angiogenesis , pathology , western blot , oncology , medicine , gene expression , microsatellite , allele , biochemistry , gene
Maspin, a member of the serpin family, has been reported to suppress metastasis and angiogenesis in breast and prostate cancers. Overexpression of maspin was associated with adverse prognostic features in several other tumours. In this study, expression of maspin was analysed in 41 colorectal carcinomas with high‐frequency microsatellite instability (MSI‐H) and 159 microsatellite stable colorectal cancers (MSS/MSI‐L) by immunohistochemistry (IHC) and partly by relative quantitative real‐time RT‐PCR and western blot analyses. Significant upregulation of maspin expression was found in MSI‐H tumours compared to both MSS/MSI‐L tumours and matched benign colonic mucosa. Increased maspin expression was also found in three MSI‐H colon cancer cell lines, but not in three MSS colon cancer cell lines by RT‐PCR and western blot analyses. Regulation of maspin expression depended on promoter methylation as tissue specimens and cell lines expressing maspin showed unmethylated maspin promoters, whereas promoter hypermethylation was found in specimens with loss of maspin expression. Intense nuclear maspin immunostaining was seen specifically in MSI‐H tumours ( p = 0.013), de‐differentiated tumours ( p = 0.006), and at the invasion front. These findings provide new insights into the role of maspin in colorectal cancer progression and may be useful for diagnosis and treatment strategies. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.