title: Preoperatively irradiated rectal carcinoma: analysis of the histopathologic response and predictive value of proliferating cell nuclear antigen immunostaining.
abstract: OBJECTIVE
  To investigate the relationship between the histopathologic effects of preoperative chemoradiotherapy in rectal cancer and the proteins, proliferating cell nuclear antigen (PCNA) and p53.
  
  
  METHODS
  Samples from 73 tumors were examined. The histopathologic effects observed in the resected specimens induced by preoperative chemoradiotherapy were correlated with the inmunohistochemical expression of PCNA and p53 in biopsies obtained by rectoscopy before chemoradiotherapy.
  
  
  RESULTS
  Thirty-five tumors showed a high PCNA index (48%). Nuclear accumulation of p53 protein was detected in 53 tumors (72%). Specimens were assigned one of four grades based on the amount of residual viable tumor. Three neoplasms (4%) showed complete regression; 8 other carcinomas (11%) showed only small numbers of tumor cells scattered within the field of stromal reaction. In these cases, it was considered that the tumor had responded significantly to radiotherapy. Tumors with a high PCNA index responded to chemoradiotherapy more frequently (8/35; 72%) than tumors with a low index (3/38; 43%) (p = 0.07). p53-negative tumors responded more frequently (4/20; 20%) than positive tumors (7/53; 13.2%) (p = 0.50). When pathologic and immunohistochemical characteristics of the tumors were included in a logistic regression model, only high PCNA index (odds ratio 5.35, 95% confidence interval 1.07-26.7) (p = 0.04) was significantly associated with the histologic response to preoperative chemoradiotherapy.
  
  
  CONCLUSIONS
  High proliferative activity of rectal cancer, as determined by PCNA immunostaining, is predictive of the response to preoperative chemoradiotherapy.
authors.affiliation: Department of Surgery and Morphological Sciences, General Surgery, Hospital Príncipe de Asturias, University of Alcalá de Henares, E-28805 Madrid, Spain. mdiez@hupa.insalud.es
authors.forename: M
authors.initials: M
authors.lastname: Díez
authors.forename: P
authors.initials: P
authors.lastname: Ramos
authors.forename: M J
authors.initials: MJ
authors.lastname: Medrano
authors.forename: J M
authors.initials: JM
authors.lastname: Mugüerza
authors.forename: R
authors.initials: R
authors.lastname: Villeta
authors.forename: O
authors.initials: O
authors.lastname: Lozano
authors.forename: J
authors.initials: J
authors.lastname: Escribano
authors.forename: F
authors.initials: F
authors.lastname: Noguerales
authors.forename: A
authors.initials: A
authors.lastname: Ruíz
authors.forename: J
authors.initials: J
authors.lastname: Granell
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011300:Preoperative Care; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy* / Q000601:surgery; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53