The Oncogenetic MicroRNA 21 and Tumorsuppressive MicroRNAs 143 and 145 As Response Predictors for Multimodal Treatment of the Locally Advanced Rectal Carcinoma
Peter P. Grimminger*1, Uta Drebber2, Elfriede Bollschweiler1, Jan Brabender1, Ralf Metzger1, Arnulf H. HöLscher1, Hakan Alakus1, Magarethe Odenthal2, Daniel Vallbohmer1
1General-, Visceral- and Tumorsurgery, University Clinic Cologne, Cologne, Germany; 2Pathology, University Clinic Cologne, Cologne, Germany
Introduction: Multimodal treatment strategies have been developed to improve the prognosis of locally advanced rectal carcinoma patients. Predominantly patients with histopathological response seem to benefit from this treatment. Therefore molecular markers which help to identify responders prior treatment are needed to individualize treatment strategies. In the presented study we have analyzed the oncogenetic microRNA 21 and tumorsupressive microRNA 143 and 145 prior and after neoadjuvant radiochemotherapy to evaluate the potential predictive strength of those markers for neoadjuvant treatment.Methods: 40 patients (24 male, 16 female; median age 61 years) with locally advanced rectal carcinoma were included in this study. All patients were treated with radiochemotherapy (50.4 Gy, 5-FU) prior curative surgery. The regression grade was defined as follows: Major responders <10% and minor responders >10% vital tumor cells in the histopathological evaluation. The intratumoral miRNA was isolated from the pretreatment biopsies and the corresponding surgically resected tumor tissue. The microRNA expression was measured using RT-PCR and correlated to clinicopathological parameters including histopathological regression data.Results: The pre- and post-treatment microRNA 21 and 143 expression did not correlate with the clinicopathological parameters or histopathological regression. The post-treatment expression of microRNA 145 showed a significant difference to the pre-treatment expression (p<0.001). During the neoadjuvant treatment the intratumoral microRNA 145 expression was significantly upregulated. A low microRNA 145 expression in the post-treatment tissue was associated with a worse histomorphological regression (p=0.04).Conclusion: The microRNA 145 expression seems to be upregulated by the neoadjuvant radiochemotherapy, however a low micro RNA 145 expression after neoadjuvant treatment was associated with a worse histopathological response. Strategies which modulate the microRNA 145 expression or the microRNA specific effect may be able to improve the effectiveness of neoadjuvant radiochemotherapy.
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