title: Hypoxia-Associated Marker CA IX Does Not Predict the Response of Locally Advanced Rectal Cancers to Neoadjuvant Chemoradiotherapy.
abstract: Hypoxia-associated proteome changes have been shown to be associated with resistance to chemo- and radiotherapy. Our study evaluated the role of the hypoxia-inducible (HIF)-1 target gene carbonic anhydrase (CA) IX in the prediction of the response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer (stages II and III). A total of 29 pretreatment biopsy specimens were stained for CA IX by immunohistochemistry, converted to digital images and evaluated in a quantitative fashion using image analysis software. Contrary to our expectations, a trend towards a correlation between better tumor regression (>50%) and higher expression of CA IX (p=0.056) was found. CA IX was also present more frequently in pathological tumor stage T1 (pT1) tumors (p=0.048). Conversely, no association with lymph node metastasis was identified. In conclusion, as a single marker, CA IX expression is not able to identify a hypoxia-related treatment resistant phenotype in rectal cancer.
authors.affiliation: Department of Radiooncology and Radiotherapy, University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany. arnmayer@uni-mainz.de.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Mayer
authors.affiliation: Department of Radiooncology and Radiotherapy, University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany. vaupel@uni-mainz.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Vaupel
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center, Mainz, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Oberholzer
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center, Mainz, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Ebert
authors.affiliation: Department of Radiooncology and Radiotherapy, University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Dimitrow
authors.affiliation: Institute of Pathology, University Medical Center, Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kreft
authors.affiliation: Institute of Physiology and Pathophysiology, University Medical Center, Mainz, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mueller-Klieser
authors.affiliation: Department of Radiooncology and Radiotherapy, University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Schmidberger
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis*; D015415:Biomarkers; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis*; D015687:Cell Hypoxia; D059248:Chemoradiotherapy; D006801:Humans; D008207:Lymphatic Metastasis; D020360:Neoadjuvant Therapy; D012004:Rectal Neoplasms / Q000201:enzymology / Q000473:pathology / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase IX; Neoadjuvant chemoradiotherapy; Rectal cancer; Tumor hypoxia; Tumor regression grading