Is MIB-1 proliferation index a predictor for response to neoadjuvant therapy in patients with esophageal cancer?
BACKGROUND
The overall survival rate for patients with an esophageal cancer remains poor. As a consequence, preoperative chemoradiation was introduced for patients with tumor stage T >1 M0 regardless of tumor histology or localization. However, factors predicting response to this therapy pretherapeutically are largely unknown.


METHODS
Clinical results of preoperative chemoradiation were investigated. The rates of proliferation and apoptosis were determined in pretherapeutic tumor samples and correlated with tumor response and long-term survival after surgery.


RESULTS
A complete tumor response due to chemoradiation (n = 42; cervically localized tumors excluded) was achieved in 11 patients (26%) after resection. Five-year survival rate was significantly improved in these patients compared with those who did not respond to chemoradiation (48% versus 5.5%; P = 0.003). Chemoradiation was performed without benefit in 43%. Perioperative hospital mortality rate was 14.3% in all patients. No correlation of apoptosis with response to chemoradiation or postoperative long-term survival was observed. However, there was a clear correlation between the proliferation rate as determined by MIB-1 immunohistology. Five-year survival rate of patients with a proliferation index (PI) >/=39% was 38% compared with 0% in tumors with a PI <39%. Tumors with a PI >/=39% responded to chemoradiation in 71.4%, but 100% of tumors with a PI <39% did not. Mean survival time of these patients was 33 months and 11 months, respectively (P = 0.015).


CONCLUSIONS
The results indicate that the PI may be used for stratification of patients treatment prior surgery. However, these results need further validation in larger patient numbers in the search for factors indicating response pretherapeutically to preoperative chemoradiation in esophageal cancer.
Imdahl
A
A
Department of Surgery, University of Freiburg, Freiburg, Germany.
Jenkner
J
J
Ihling
C
C
Rückauer
K
K
Farthmann
E H
EH
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000032:analysis; D034961:Antigens, Nuclear; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002455:Cell Division; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D016629:Esophagectomy / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011336:Probability; D018714:Radiotherapy, Adjuvant; D018709:Statistics, Nonparametric; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009687:Nuclear Proteins