Aberrant expression of maspin in idiopathic inflammatory bowel disease is associated with disease activity and neoplastic transformation.
BACKGROUND
Maspin is both overexpressed in tumors and inflammation, implicating a possible role in bridging inflammation and neoplasia. Idiopathic inflammatory bowel disease (IBD) and IBD-associated dysplasias and carcinomas represent a prototype for studying the relationship between chronic inflammatory states and neoplasia.


OBJECTIVE
To investigate expression of maspin in IBD and IBD-associated dysplasia and colorectal carcinoma.


METHODS
Immunohistochemical labeling of maspin was examined using tissue microarrays constructed from archival biopsy and resection tissue from 90 patients with 125 histologically defined lesions including 30 with inactive chronic IBD, 51 with active chronic IBD, 4 IBD-associated foci with epithelial changes indefinite for dysplasia (IFD), 7 with IBD-associated low-grade epithelial dysplasia (LGD), 8 with IBD-associated high grade epithelial dysplasia (HGD), and 25 with IBD-associated invasive colorectal adenocarcinomas.


RESULTS
Maspin was expressed in 47/51 (92%) active chronic IBD lesions, which was significantly higher than both inactive chronic IBD (13/30, 43%) and normal mucosa (1 of 9, 11%) (p < 0.01); in particular, the diffuse pattern of maspin expression was significantly higher in active IBD (41/51, 80%), compared with inactive IBD (5/30, 17%) and normal mucosa (0%) (p < 0.01). In the multistage progression model of colitis-associated neoplasia, aberrant labeling was observed at the earliest stages, with 3/4 (75%) IFD foci, 6/7 (86%) LGD, and 8/8 (100%) HGD specimens expressing maspin, virtually always in a diffuse pattern. Expectedly, 22/25 (88%) of invasive IBD-associated cancers overexpressed maspin, including 21 with diffuse labeling.


CONCLUSIONS
Maspin is significantly overexpressed in both active IBD and colitis-associated dysplasia compared to either inactive IBD or normal colonic mucosa, suggesting a potential role in disease "flare" as well as neoplastic progression. Targeting maspin for control of disease activity and cancer prophylaxis may be a promising novel therapeutic strategy for IBD.
Cao
Dengfeng
D
Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland 21231, USA. dcao1@jhmi.edu
Wilentz
Robb E
RE
Abbruzzese
James L
JL
Ho
Linus
L
Maitra
Anirban
A
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D001706:Biopsy; D002471:Cell Transformation, Neoplastic; D003092:Colitis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D015843:Serpins / Q000096:biosynthesis* / Q000235:genetics
C085344:SERPIN-B5; D015843:Serpins