This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Galizia, G. Articles by Pignatelli, C. Search for Related Content PubMed PubMed Citation Articles by Galizia, G. Articles by Pignatelli, C.

Determination of Molecular Marker Expression Can Predict Clinical Outcome in Colon Carcinomas

Divisions of ¹ Surgical Oncology, ² Pathology, and ³ Medical Oncology, and ⁴ Division of Internal Medicine, Allergy and Clinical Immunology; "F. Magrassi and A. Lanzara" Department of Clinical and Experimental Medicine and Surgery; Second University of Naples School of Medicine, Naples, Italy

Purpose: Conventional staging procedures are often unable to precisely predict prognosis in colorectal cancer (CRC). In this study, we set out to investigate the possible role of molecular/structural indicators involved in cell cycle regulation (p27 and p53), apoptosis (p53 and p27), and tumor neoangiogenesis [p53, vascular endothelial growth factor (VEGF), and microvessel count] in predicting tumor behavior and clinical outcome in CRC patients

Experimental Design: Analysis of the above indicators was performed by immunohistochemistry on 104 CRC patient samples and 25 normal colon mucosa specimens.

Results: Intense p27 nuclear staining was found in normal colon mucosa, with p53 nuclear staining and VEGF cytoplasmic accumulation <10%, and low microvessel count. In contrast, in CRC samples, p27 was down-regulated in 53.8%, p53 protein was overexpressed in 52%, and VEGF stained positive in 67.3% of the cases, respectively. Multiple regression analysis showed that molecular markers were strongly correlated. In patients treated with curative surgery, a significant relationship was seen between p27 down-regulation and Dukes’ stage, nodal status, and the presence of distant metastases. VEGF overexpression correlated significantly with Dukes’ stage, tumor (t) and metastasis (m) parameters, and left site. Stepwise regression selected p27, p53, VEGF, and Dukes’ stage as the best combination of variables capable of predicting both disease-specific and disease-free survival.

Conclusions: The investigated indicators may be useful for the prediction of outcome and recurrence rate in curatively treated CRC patients. In conjunction with clinical and pathological staging, they may provide a stronger indication of clinical outcome than staging alone and help better select therapeutic options in CRC patients.

This article has been cited by other articles:

				S. K. Chang, I. Rizvi, N. Solban, and T. Hasan In vivo Optical Molecular Imaging of Vascular Endothelial Growth Factor for Monitoring Cancer Treatment Clin. Cancer Res., July 1, 2008; 14(13): 4146 - 4153. [Abstract] [Full Text] [PDF]

				E. Lieto, F. Ferraraccio, M. Orditura, P. Castellano, A. La Mura, M. Pinto, A. Zamboli, F. DeVita, and G. Galizia Expression of Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) is an Independent Prognostic Indicator of Worse Outcome in Gastric Cancer Patients Ann. Surg. Oncol., January 1, 2008; 15(1): 69 - 79. [Abstract] [Full Text] [PDF]

				J. G. Kim, Y. S. Chae, S. K. Sohn, Y. Y. Cho, J. H. Moon, J. Y. Park, S. W. Jeon, I. T. Lee, G. S. Choi, and S.-H. Jun Vascular Endothelial Growth Factor Gene Polymorphisms Associated with Prognosis for Patients with Colorectal Cancer Clin. Cancer Res., January 1, 2008; 14(1): 62 - 66. [Abstract] [Full Text] [PDF]

				I. Zlobec, R. Steele, L. Terracciano, J. R Jass, and A. Lugli Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer J. Clin. Pathol., October 1, 2007; 60(10): 1112 - 1116. [Abstract] [Full Text] [PDF]

				R. H. Nakamoto, H. Uetake, S. Iida, Y. V. Kolev, L. T. Soumaoro, Y. Takagi, M. Yasuno, and K. Sugihara Correlations between Cyclooxygenase-2 Expression and Angiogenic Factors in Primary Tumors and Liver Metastases in Colorectal Cancer Jpn. J. Clin. Oncol., September 10, 2007; (2007) hym080v1. [Abstract] [Full Text] [PDF]

				F. Al-Mulla, S. Hagan, A. I. Behbehani, M. S. Bitar, S. S. George, J. J. Going, J. J. C. Garcia, L. Scott, N. Fyfe, G. I. Murray, et al. Raf Kinase Inhibitor Protein Expression in a Survival Analysis of Colorectal Cancer Patients J. Clin. Oncol., December 20, 2006; 24(36): 5672 - 5679. [Abstract] [Full Text] [PDF]

				G. Galizia, E. Lieto, F. Ferraraccio, F. De Vita, P. Castellano, M. Orditura, V. Imperatore, A. La Mura, G. La Manna, M. Pinto, et al. Prognostic Significance of Epidermal Growth Factor Receptor Expression in Colon Cancer Patients Undergoing Curative Surgery Ann. Surg. Oncol., June 1, 2006; 13(6): 823 - 835. [Abstract] [Full Text] [PDF]

				M. S. Lyall, S. R. Dundas, S. Curran, and G. I. Murray Profiling Markers of Prognosis in Colorectal Cancer Clin. Cancer Res., February 15, 2006; 12(4): 1184 - 1191. [Abstract] [Full Text] [PDF]

				A. M. Jubb, H. I. Hurwitz, W. Bai, E. B. Holmgren, P. Tobin, A. S. Guerrero, F. Kabbinavar, S. N. Holden, W. F. Novotny, G. D. Frantz, et al. Impact of Vascular Endothelial Growth Factor-A Expression, Thrombospondin-2 Expression, and Microvessel Density on the Treatment Effect of Bevacizumab in Metastatic Colorectal Cancer J. Clin. Oncol., January 10, 2006; 24(2): 217 - 227. [Abstract] [Full Text] [PDF]

				T. Hata, H. Yamamoto, C. Y. Ngan, M. Koi, A. Takagi, B. Damdinsuren, M. Yasui, Y. Fujie, T. Matsuzaki, H. Hemmi, et al. Role of p21waf1/cip1 in effects of oxaliplatin in colorectal cancer cells Mol. Cancer Ther., October 1, 2005; 4(10): 1585 - 1594. [Abstract] [Full Text] [PDF]

				I. Zlobec, R. Steele, N. Nigam, and C. C. Compton A Predictive Model of Rectal Tumor Response to Preoperative Radiotherapy Using Classification and Regression Tree Methods Clin. Cancer Res., August 1, 2005; 11(15): 5440 - 5443. [Abstract] [Full Text] [PDF]