title: Relevance of biologic markers in colorectal carcinoma: a comparative study of a broad panel.
abstract: BACKGROUND
  Although pathologic stage is currently the main prognostic indicator for patients with colorectal carcinoma (CRC), mounting evidence suggests that, in its current form, it is insufficient to predict clinical outcome. To assess biologic markers of primary CRC that may improve clinical staging and provide useful information for the application of novel therapeutic strategies, the authors investigated a panel of markers that included transforming growth factor alpha (TGF alpha), epithelial growth factor receptor (EGF-R; the protein product of the c-erb B2/HER-2 oncogene), matrix metalloproteinase 2 (MMP-2), insulin-like growth factor II (IGF-II), vascular endothelial growth factor (VEGF), and angiogenesis, as evaluated by microvessel density (MVD).
  
  
  METHODS
  Two groups of CRC were studied: 1) surgical samples from patients who achieved a disease free survival of at least 6 years (CRC-M0) and 2) surgical specimens of both primary tumors and synchronous or metachronous liver metastases (CRC-M1).
  
  
  RESULTS
  Chi-square analysis revealed that expression levels of TGF-alpha, c-erb B2/HER-2, MMP-2, IGF-II, VEGF, and MVD (but not EGF-R) were significantly higher in CRC-M1 samples compared with CRC-M0 samples (P < 0.001, P < 0.05, P < 0.001, P < 0.001, P < 0.01, and P < 0.001, respectively). Logistic regression analysis showed that TGF-alpha, IGF-II, and MMP-2 had significantly greater expression in CRC-M1 samples independent of the other variables (including tumor classification, histologic grade, and patient age). If all three markers had > or = 25% expression, then the probability of developing liver metastasis was 99.5%.
  
  
  CONCLUSIONS
  Based on the evidence of this study, TGF-alpha MMP-2, and IGF-II seem suitable candidates for a selective panel of markers designed to provide significant additional information with respect to the current pathologic staging system for patients with colorectal carcinoma.
authors.affiliation: Pathology Division, Department of Oncohematology, F. Addarii Institute, University School of Medicine, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Barozzi
authors.forename: Matteo
authors.initials: M
authors.lastname: Ravaioli
authors.forename: Antonia
authors.initials: A
authors.lastname: D'Errico
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Grazi
authors.forename: Gilberto
authors.initials: G
authors.lastname: Poggioli
authors.forename: Giulia
authors.initials: G
authors.lastname: Cavrini
authors.forename: Alighieri
authors.initials: A
authors.lastname: Mazziotti
authors.forename: Walter Franco
authors.initials: WF
authors.lastname: Grigioni
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000473:pathology* / Q000556:secondary; D015179:Colorectal Neoplasms / Q000473:pathology*; D018076:DNA, Complementary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016211:Transforming Growth Factor alpha / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D016211:Transforming Growth Factor alpha; D007335:Insulin-Like Growth Factor II; D020778:Matrix Metalloproteinase 2