Gender-related differences in pathological and clinical tumor response based on immunohistochemical proteins expression in rectal cancer patients treated with short course of preoperative radiotherapy

J Gastrointest Surg. 2014 Jul;18(7):1306-18. doi: 10.1007/s11605-014-2526-0. Epub 2014 Apr 23.

Abstract

Background: Prognostic value of pretreatment expression of proteins in rectal cancer for early pathological tumor response (pTR), clinical tumor response (CTR) to preoperative radiotherapy (RT), and the potential difference between these parameters depending on patient gender is not established.

Material and methods: One hundred eleven patients were treated with short preoperative course of RT (SCRT) with 5 Gy dose per fraction during 5 days, followed by surgery 3 to 53 days (mean, 21 days) later. Expression of CD34, Ki-67, GLUT-1, Ku70, BCL-2, and P53 proteins was assessed immunohistochemically.

Results: There were 76 men and 35 women. There were 27, 69, and 15 clinical tumor-node-metastasis (cTNM) tumor stages I, II, and III, respectively. Significant differences in Ki-67, GLUT-1, Ku 70, and BCL-2 expressions between male and female tumors were observed for pathological TNM (pTNM) stage and grade. Association between proteins expression and pTNM, pTR, and CTR was analyzed separately for short (≤15 days) and long (>15 days) break between RT and surgery and males and female patients. For SCRT with short break, no protein was significantly related to pTNM; for pTR, higher Ki-67 and lower BCL-2 expression were correlated with pTR. In the male subgroup, BCL-2 overexpression was predictive. For SCRT with long break, none of the proteins was predictive for pTR, but Ki-67, Ku70 (in female subgroup), and BCL-2 expressions were positively correlated with pTNM. BCL-2 overexpression was associated with CTR in the females only.

Conclusion: In SCRT, long break in the treatment should be avoided because correlation between Ki-67, KU70, and BCL-2 expressions and pTNM after RT might indicate tumor progression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / surgery*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Biopsy, Needle
  • Cohort Studies
  • Disease-Free Survival
  • Dose-Response Relationship, Radiation
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Neoplasm Staging
  • Preoperative Care / methods
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Radiotherapy Dosage
  • Rectal Neoplasms / metabolism
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery*
  • Retrospective Studies
  • Risk Assessment
  • Sex Factors
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2