TY - JOUR
T1 - Hypoxia-related proteins in patients with rectal cancer undergoing neoadjuvant combined modality therapy
AU - Lee-Kong, Steven A.
AU - Ruby, Jeannine A.
AU - Chessin, David B.
AU - Pucciarelli, Salvatore
AU - Shia, Jinru
AU - Riedel, Elyn R.
AU - Nitti, Donato
AU - Guillem, José G.
PY - 2012/9
Y1 - 2012/9
N2 - BACKGROUND: We have previously demonstrated the prognostic significance of rectal cancer pathologic response to neoadjuvant chemoradiation. Recent studies in other cancers have reported that hypoxia influences response to neoadjuvant chemoradiation. OBJECTIVE: This study aimed to 1) characterize hypoxiarelated protein expression in locally advanced rectal cancer before neoadjuvant chemoradiation, 2) determine the comodulation of hypoxia-related protein expression, and 3) evaluate the relationship between hypoxiarelated protein expression and overall survival, time to recurrence, and tumor regression grade. DESIGN: Immunohistochemical analysis of 4 hypoxiarelated proteins (HIF-1α, CA-IX, VEGF, and GLUT-1) was performed on archival pretreatment rectal cancer biopsies. PATIENTS: Eighty-five patients with locally advanced rectal cancer treated with neoadjuvant radiation and 5-fluorouracil-based chemotherapy were included. MAIN OUTCOME MEASURES: The impact of hypoxiarelated protein expression on outcome was evaluated by use of Cox proportional hazards model. Hypoxia-related protein expression was correlated with tumor regression grade by use of Spearman correlation coefficients. RESULTS: Median follow-up was 54 months. CA-IX expression was associated with overall survival (p = 0.01). HIF-1α expression was weakly correlated with VEGF (r = 0.26, p = 0.02) and GLUT-1 (r = 0.35, p = 0.001). Hypoxia-related protein expression was not associated with time to recurrence or Mandard tumor regression grade. CONCLUSIONS: Elevated CA-IX expression may be associated with poorer overall survival in locally advanced rectal cancer treated by neoadjuvant chemoradiation and resection. The expression of the hypoxia-related proteins HIF-1α, VEGF, and GLUT-1 may be comodulated in locally advanced rectal cancer. Further studies are needed to evaluate the mechanisms governing hypoxia regulation and the role of hypoxia in rectal cancer response to neoadjuvant chemoradiation.
AB - BACKGROUND: We have previously demonstrated the prognostic significance of rectal cancer pathologic response to neoadjuvant chemoradiation. Recent studies in other cancers have reported that hypoxia influences response to neoadjuvant chemoradiation. OBJECTIVE: This study aimed to 1) characterize hypoxiarelated protein expression in locally advanced rectal cancer before neoadjuvant chemoradiation, 2) determine the comodulation of hypoxia-related protein expression, and 3) evaluate the relationship between hypoxiarelated protein expression and overall survival, time to recurrence, and tumor regression grade. DESIGN: Immunohistochemical analysis of 4 hypoxiarelated proteins (HIF-1α, CA-IX, VEGF, and GLUT-1) was performed on archival pretreatment rectal cancer biopsies. PATIENTS: Eighty-five patients with locally advanced rectal cancer treated with neoadjuvant radiation and 5-fluorouracil-based chemotherapy were included. MAIN OUTCOME MEASURES: The impact of hypoxiarelated protein expression on outcome was evaluated by use of Cox proportional hazards model. Hypoxia-related protein expression was correlated with tumor regression grade by use of Spearman correlation coefficients. RESULTS: Median follow-up was 54 months. CA-IX expression was associated with overall survival (p = 0.01). HIF-1α expression was weakly correlated with VEGF (r = 0.26, p = 0.02) and GLUT-1 (r = 0.35, p = 0.001). Hypoxia-related protein expression was not associated with time to recurrence or Mandard tumor regression grade. CONCLUSIONS: Elevated CA-IX expression may be associated with poorer overall survival in locally advanced rectal cancer treated by neoadjuvant chemoradiation and resection. The expression of the hypoxia-related proteins HIF-1α, VEGF, and GLUT-1 may be comodulated in locally advanced rectal cancer. Further studies are needed to evaluate the mechanisms governing hypoxia regulation and the role of hypoxia in rectal cancer response to neoadjuvant chemoradiation.
UR - https://www.scopus.com/pages/publications/84866017041
UR - https://www.scopus.com/pages/publications/84866017041#tab=citedBy
U2 - 10.1097/DCR.0b013e31825bd80c
DO - 10.1097/DCR.0b013e31825bd80c
M3 - Article
C2 - 22874607
AN - SCOPUS:84866017041
SN - 0012-3706
VL - 55
SP - 990
EP - 995
JO - Diseases of the colon and rectum
JF - Diseases of the colon and rectum
IS - 9
ER -
