title: Molecular Marker Expression Is Highly Heterogeneous in Esophageal Adenocarcinoma and Does Not Predict a Response to Neoadjuvant Therapy.
abstract: A reliable method to identify pathologic complete responders (pCR) or non-responders (NR) to neoadjuvant chemoradiation therapy (NAT) would dramatically improve therapy for esophageal cancer. The purpose of this study is to investigate if a distinct profile of prognostic molecular markers can predict pCR after neoadjuvant therapy. Expression of p53, Her-2/neu, Cox-2, Beta-catenin, E-cadherin, MMP-1, NFkB, and TGF-B was measured by immunohistochemistry in pre-treatment biopsy tissue and graded by an experienced pathologist. A pCR was defined as no evidence of malignancy on final pathology. Molecular profiles comparing responders to non-responders were analyzed using classification and regression tree analysis to investigate response to NAT and overall survival. Nineteen patients were pCRs and 34 were NRs. pCRs were more likely to be alive at follow-up than NRs (p < 0.01). Thirty-seven distinct profiles were identified. Expression of molecular markers was highly heterogeneous between patients and did not correlate with a response to NAT, survival (p = 0.47) or clinical stage (p = 0.39) when evaluated either as individual markers or in combination with other expression patterns. NAT dramatically impacts survival through a mechanism independent of known molecular markers of esophageal cancer, which are expressed in a highly heterogeneous fashion and do not predict response to NAT or survival.
authors.affiliation: Department of Surgery, Division of Gastrointestinal and General Surgery, and The Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Bronson
authors.affiliation: Department of Surgery, Division of Gastrointestinal and General Surgery, and The Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Diggs
authors.affiliation: Department of Medicine, Division of Gastroenterology, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Gene
authors.initials: G
authors.lastname: Bakis
authors.affiliation: Department of Pathology, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Gatter
authors.affiliation: Department of Surgery, Division of Gastrointestinal and General Surgery, and The Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Brett C
authors.initials: BC
authors.lastname: Sheppard
authors.affiliation: Department of Surgery, Division of Gastrointestinal and General Surgery, and The Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Hunter
authors.affiliation: Department of Surgery, Division of Gastrointestinal and General Surgery, and The Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. dolanj@ohsu.edu.
authors.forename: James P
authors.initials: JP
authors.lastname: Dolan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D059248:Chemoradiotherapy; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D015820:Cadherins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D051176:beta Catenin; D051546:Cyclooxygenase 2; D020781:Matrix Metalloproteinase 1
keywords: Esophageal cancer; Molecular marker; Neoadjuvant therapy; Oesophageal cancer; Tumor profile