title: Expression of apoptosis-regulating proteins and outcome of esophageal cancer patients treated by combined therapy modalities.
abstract: The present study retrospectively examines the correlation between the outcome of patients with locally advanced esophageal squamous cell carcinoma (LAEC) after multimodal treatment (radiochemotherapy +/- surgery) and the expression of apoptosis-regulating proteins in pretherapeutic biopsies. Thirty-eight patients with LAEC who took part in a prospective multicentric trial received radiochemotherapy, optionally followed by surgery. Pretreatment tumor biopsies were immunohistochemically investigated for expression of p53, Bcl-2, Bax (bcl-2-associated X protein), and Bcl-X(L) (bcl-2-related X protein). The overall expression of p53, Bcl-2, Bax, and Bcl-X(L) was 52.6, 57.9, 100, and 97.4% respectively. Tumors without p53 expression and tumors with weak Bcl-X(L) expression showed response to chemotherapy more frequently (55.6 and 52.6%, respectively) than tumors positive for p53 expression and tumors with strong Bcl-X(L) expression (30.0 and 31.6%, respectively); however, these differences did not attain statistical significance. No correlations were found between the expression of Bcl-2 and Bax and the response to chemotherapy. In patients treated by radiochemotherapy and surgery, p53-negative tumors showed a significantly better outcome than p53-positive tumors (mean survival, 31.1 months versus 11.3 months; P = 0.0378). Additionally, a more favorable outcome was observed in tumors positive for Bcl-2 (not significant), whereas no differences in survival were observed in relation to the expression of Bax or Bcl-X(L). No differences in survival were observed in patients treated by radiochemotherapy without subsequent resection therapy in relation to the expression of apoptosis-regulating proteins. Immunohistochemical examination of pretherapeutic tumor biopsies for expression of apoptosis-regulating proteins may help to identify patients with LAEC who may benefit from multimodal treatment and those who may not.
authors.affiliation: Department of Pathology, Heinrich-Heine Universität, Düsseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sarbia
authors.forename: M
authors.initials: M
authors.lastname: Stahl
authors.forename: U
authors.initials: U
authors.lastname: Fink
authors.forename: R
authors.initials: R
authors.lastname: Willers
authors.forename: S
authors.initials: S
authors.lastname: Seeber
authors.forename: H E
authors.initials: HE
authors.lastname: Gabbert
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D004848:Epithelium / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D004947:Esophagus / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012189:Retrospective Studies; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein