title: Prognostic and predictive value of baseline and posttreatment molecular marker expression in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.
abstract: OBJECTIVE
  To evaluate expression of a panel of molecular markers, including p53, p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after treatment in patients treated with neoadjuvant chemoradiotherapy for locally advanced rectal cancer, to correlate the constitutive profile and dynamics of expression with pathologic response and outcome.
  
  
  METHODS
  Expression of biomarkers was evaluated by immunohistochemistry in tumor samples from 91 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by continuous intravenous infusion.
  
  
  RESULTS
  A pathologic complete remission was observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of constitutive p21, absence of EGFR expression after chemoradiotherapy, and high Dworak's tumor regression grade (TRG) were significantly associated with improved disease-free survival and overall survival. A high MIB-1 value after chemoradiotherapy was significantly associated with worse overall survival. Multivariate analysis confirmed the prognostic value of constitutive p21 expression as well as EGFR expression and MIB-1 value after chemoradiotherapy among patients not achieving TRG 3-4.
  
  
  CONCLUSIONS
  In our study, we observed the independent prognostic value of EGFR expression after chemoradiotherapy on disease-free survival. Moreover, our study suggests that a constitutive high p21 expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment could predict worse outcome in locally advanced rectal cancer.
authors: Division of Medical Oncology, Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy. bertolini.federica@policlinico.mo.it
authors: Federica
authors: F
authors: Bertolini
authors: Carmelo
authors: C
authors: Bengala
authors: Luisa
authors: L
authors: Losi
authors: Maria
authors: M
authors: Pagano
authors: Francesco
authors: F
authors: Iachetta
authors: Cristina
authors: C
authors: Dealis
authors: Gordana
authors: G
authors: Jovic
authors: Roberta
authors: R
authors: Depenni
authors: Sandra
authors: S
authors: Zironi
authors: Anna Maria
authors: AM
authors: Falchi
authors: Gabriele
authors: G
authors: Luppi
authors: Pier Franco
authors: PF
authors: Conte
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D020360:Neoadjuvant Therapy; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D013940:Thymidylate Synthase; D066246:ErbB Receptors; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein