title: MMP3 and CXCL1 are potent stromal protein markers of dysplasia-carcinoma transition in sporadic colorectal cancer.
abstract: Early molecular detection of the colorectal dysplasia-carcinoma transition may augment the accuracy of diagnosis in case of biopsy orientation errors. The combination of high-throughput microarray-based biomarker screening with tissue microarray-based prospective protein biomarker expression analysis could represent an additional test in routine automated diagnostic procedures. Our aim was to test and select protein markers to identify protein expression profile alterations, focusing on the dysplasia-carcinoma transition in sporadic colorectal tumors. Dysplasia-carcinoma transition-specific transcript sets were previously identified using HGU133plus2 microarrays and Taqman RT-PCR cards. Here, 26 potential dysplasia-carcinoma transition-specific markers were tested by immunohistochemistry at the protein level using tissue microarrays in a total of 168 independent colonic biopsy samples. A set of 26 transcripts [including matrix metalloproteinase-3 (MMP3) and chemokine (C-X-C motif) ligand 1 (CXCL1)] has been determined recently, indicating a linear expression correlation with the adenoma-dysplasia-carcinoma sequence, thereby having the potential to discriminate between dysplasia and early malignancy. Currently, we find that high-grade dysplastic sessile adenomatous-stage and early-stage colorectal cancer conditions can be differentiated correctly by the stromal expression of MMP3 and CXCL1, respectively, on tissue microarray-based analysis. Furthermore, in cases of sporadic colorectal tumors, MMP3 protein expression in the lamina propria itself seems to be highly specific for the detection of tumorous transition. Our current and recent results indicate that appropriate antibody marker combinations are highly suitable for tissue microarray-based and digital microscopy-based, automated, high-capacity diagnostic application in tumorous colonic diseases.
authors.affiliation: a2nd Department of Internal Medicine bFaculty of Medicine, Department of Medicine c1st Department of Pathology and Experimental Cancer Research, Semmelweis University dMolecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sipos
authors.forename: Tiana M
authors.initials: TM
authors.lastname: Germann
authors.forename: Barnabás
authors.initials: B
authors.lastname: Wichmann
authors.forename: Orsolya
authors.initials: O
authors.lastname: Galamb
authors.forename: Sándor
authors.initials: S
authors.lastname: Spisák
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenács
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Béla
authors.initials: B
authors.lastname: Molnár
authors.forename: Györgyi
authors.initials: G
authors.lastname: Műzes
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D006965:Hyperplasia / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D012333:RNA, Messenger; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3