Failure in downregulation of intratumoral survivin expression following neoadjuvant chemoradiation in esophageal cancer.
BACKGROUND
Neoadjuvant multimodality treatment is frequently applied to improve the poor prognosis associated with locally advanced esophageal cancer. However, only patients with a major histopathologic response to neoadjuvant therapy will have a significant survival benefit. Predictive markers to allow individualization of multimodality treatment could be very helpful. We aimed to examine the association of survivin protein expression, an inhibitor of apoptosis, with histopathologic response to neoadjuvant chemoradiation and prognosis in patients with esophageal cancer.


METHODS
A total of 59 patients with esophageal cancer (clinical tumor stage 2-4, N(x), M(0)) received neoadjuvant chemoradiation followed by transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10% vital tumor cells. Intratumoral survivin expression was determined by immunohistochemistry in pretherapeutic biopsies and post-therapeutic resection specimens and correlated with clinicopathologic parameters.


RESULTS
The pretherapeutic intratumoral survivin protein expression was not associated with any clinicopathologic factor. Survivin protein expression decreased significantly during neoadjuvant therapy, showing lower levels in post-therapeutic tumor samples (p < 0.01). Elevated postoperative survivin levels were significantly associated with a higher pathologic tumor stage after neoadjuvant therapy (ypT) category (p < 0.01), a poorer histopathologic response (p < 0.01) and a shorter overall survival (p < 0.028).


CONCLUSIONS
Intratumoral survivin protein expression was significantly downregulated during neoadjuvant therapy of esophageal cancers. Elevated survivin levels after preoperative therapy were significantly associated with a minor histopathologic response and prognosis. Therefore, failure in downregulation of intratumoral survivin expression following neoadjuvant chemoradiation in esophageal cancer needs therapeutic strategies to reduce survivin expression or block survivin-mediated pathways to increase the histopathologic response rate and prognosis.
Vallböhmer
Daniel
D
Department of Visceral and Vascular Surgery, University of Cologne, Kerpenerstrasse 62, 50937 Cologne, Germany.
Kuhn
Elmar
E
Warnecke-Eberz
Ute
U
Brabender
Jan
J
Hoffmann
Andreas C
AC
Metzger
Ralf
R
Baldus
Stephan E
SE
Drebber
Uta
U
Hoelscher
Arnulf H
AH
Schneider
Paul M
PM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009367:Neoplasm Staging; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D000077022:Survivin; D017211:Treatment Failure
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D002945:Cisplatin; D005472:Fluorouracil