Colonic expression of heme oxygenase-1 is associated with a better long-term survival in patients with colorectal cancer.
OBJECTIVE
Heme oxygenase-1 (HO-1) has emerged as a crucial mediator of mucosal defense in the gastrointestinal tract. Its metabolic pathway products, biliverdin/bilirubin and carbon monoxide, can reduce oxidative stress and inflammation, and promote resistance to apoptosis. The role of HO-1 in gastrointestinal malignancies, however, remains to be elucidated. The purpose of this study was to analyze HO-1 expression in human colon adenoma and cancer samples.


METHODS
Fifty-five paraffin-embedded surgical specimens of colorectal cancer and 19 colonic adenoma samples were stained immunhistochemically for HO-1 expression using an anti-HO-1 monoclonal antibody. HO-1 expression was evaluated independently by two different investigators and subsequently correlated to clinical data and patients' life expectancy.


RESULTS
Focal HO-1 expression could be documented in 41.8% (23/55) of patients with colorectal cancer. HO-1 expression in colonic adenoma was detectable in 36.8% (7/19) of cases. The rate of lymphatic tumor invasion was significantly lower in colorectal cancer samples expressing HO-1 (p=0.048). Additionally, fewer lymph node metastases were found in colorectal cancer samples with HO-1 expression, but these differences did not reach statistical significance. Mean observation period was 65.87+/-3.96 months. Kaplan-Meier analysis showed a significantly better survival for colorectal cancer patients with colonic HO-1 expression (p=0.018).


CONCLUSIONS
This study demonstrates that colonic HO-1 may be a prognostic marker of colorectal-cancer outcome.
Becker
Jan C
JC
Department of Medicine B, University of Münster, Münster, Germany.
Fukui
Hirokazu
H
Imai
Yasuo
Y
Sekikawa
Akira
A
Kimura
Tokiko
T
Yamagishi
Hidetsugu
H
Yoshitake
Naoto
N
Pohle
Thorsten
T
Domschke
Wolfram
W
Fujimori
Takahiro
T
D000236:Adenoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003106:Colon / Q000201:enzymology*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
D014408:Biomarkers, Tumor; D051547:Heme Oxygenase-1