Elevated nuclear maspin expression is associated with microsatellite instability and high tumour grade in colorectal cancer.
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.
Bettstetter
Marcus
M
Department of Pathology, University of Regensburg, D-93053 Regensburg, Germany.
Woenckhaus
Matthias
M
Wild
Peter J
PJ
Rümmele
Petra
P
Blaszyk
Hagen
H
Hartmann
Arndt
A
Hofstädter
Ferdinand
F
Dietmaier
Wolfgang
W
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018899:CpG Islands; D003593:Cytoplasm / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C085344:SERPIN-B5; D015843:Serpins