title: Overexpression of survivin mRNA is associated with a favorable prognosis following neoadjuvant radiochemotherapy in esophageal cancer.
abstract: Survivin is a member of the inhibitor of apoptosis (IAP) gene family known to be involved in resistance to chemo- and radiation therapy. We examined the potential of quantitative survivin mRNA expression to predict histopathologic tumor response and prognosis following neoadjuvant radiochemotherapy (cis-platinum, 5-FU, 36 Gy) in patients with locally-advanced esophageal cancer (cT2-4, Nx, M0). Tumor (T) and normal tissue (N) samples from 51 patients were collected by endoscopic biopsy prior to treatment. Survivin mRNA expression was analyzed by quantitative real-time RT-PCR assays. Histomorphologic regression was defined as a major response when resected specimens contained <10% of residual vital tumor cells or if a pathologically complete response was achieved. Some 7/51 patients had progressive disease and 44/51 proceeded to surgical resection. Of 44 resected tumors, 17 (31.4%) showed a major and 27 (61.4%) showed a minor histopathologic response; the survival rates were significantly different (p<0.01). Median absolute survivin expression was 5.1 in the tumor and 2.4 in corresponding normal tissue samples (Wilcoxon, p<0.001). Median relative (T/N ratio) survivin mRNA expression was 1.7. Survivin mRNA expression levels did not show a significant association with histomorphologic regression. Relative survivin mRNA expression of a T/N ratio >1 indicated a favorable prognosis (log-rank, p<0.003). Expression levels of survivin mRNA in pretherapeutic biopsies did not predict the extent of histomorphologic tumor regression following preoperative radiochemotherapy for esophageal cancer. However, overexpression of survivin mRNA in pretreatment biopsies (T/N ratio >1) was associated with superior survival probabilities.
authors.affiliation: Department of Visceral and Vascular Surgery, University of Cologne, Joseph-Stelzmann-Strasse 9, 50931 Cologne, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Warnecke-Eberz
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hokita
authors.forename: Huan
authors.initials: H
authors.lastname: Xi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Higashi
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Baldus
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
authors.forename: Jan
authors.initials: J
authors.lastname: Brabender
authors.forename: Elfriede
authors.initials: E
authors.lastname: Bollschweiler
authors.forename: Rolf P
authors.initials: RP
authors.lastname: Mueller
authors.forename: Hans P
authors.initials: HP
authors.lastname: Dienes
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hoelscher
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schneider
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000077022:Survivin; D016896:Treatment Outcome
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin; D002945:Cisplatin; D005472:Fluorouracil