predictive value of genes of the TGF-β1 pathway in multimodally treated squamous cell carcinoma of the esophagus

Background and aim Pretherapeutic identification of esophageal squamous cell carcinomas (ESCCs) that are likely to respond to neoadjuvant chemoradiotherapy is important in the attempt to improve the prognosis for patients. In the present study, expression of members of the transforming growth factor...

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Bibliographic Details
Published in:International journal of colorectal disease 2010-04, Vol.25 (4), p.515-521
Main Authors: Pühringer-Oppermann, Franziska, Sarbia, Mario, Ott, Nicola, Brücher, Björn L. D. M
Format: Article
Language:English
Subjects:
Biological and medical sciences
Esophagus
Gastroenterology
Gastroenterology. Liver. Pancreas. Abdomen
Hepatology
Internal Medicine
Medical sciences
Medicine
Medicine & Public Health
Original Article
Proctology
Surgery
Tumors
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Summary:Background and aim Pretherapeutic identification of esophageal squamous cell carcinomas (ESCCs) that are likely to respond to neoadjuvant chemoradiotherapy is important in the attempt to improve the prognosis for patients. In the present study, expression of members of the transforming growth factor-β1 (TGF-β1) signaling pathway was investigated in pretherapeutic biopsies from 97 ESCCs (cT3, cN0/+, cM0) in patients who underwent neoadjuvant chemoradiotherapy (45 Gy plus cisplatin and 5-fluorouracil) and subsequent esophagectomy in the setting of a single-center prospective treatment trial. Materials and methods Expression of TGF-β1 and its downstream effectors Smad4 and Smad7 was assessed using quantitative reverse transcription polymerase chain reaction from RNA prepared from pretherapeutic tumor biopsies. The presence of phosphorylated Smad2 was assessed immunohistochemically. Results Expression of TGF-β1 (mean 7.8; range 0.0-25.7 arb. units), Smad4 (mean 0.1; range 0.0-0.4 arb. units), and Smad7 (mean 1.6; range 0.4-16.1 arb. units) varied substantially between the patients. Tumors with total or subtotal regression, as determined by histopathological examination after neoadjuvant chemoradiotherapy, showed significantly higher levels of Smad4 mRNA expression than tumors with minor or no regression (P = 0.032). TGF-β1 and Smad7 mRNA expression as well as Smad2 protein expression were of no prognostic value. Expression of the four genes under analysis also showed no impact on the overall survival. In contrast, the overall survival correlated significantly with histopathological regression (P 
ISSN:0179-1958
1432-1262
DOI:10.1007/s00384-009-0867-z