Molecular and clinical differences between adenocarcinomas of the esophagus and adenocarcinomas of the cardia

P. Taniere, MD,a,b, G. Martel-Plancheb, M-L Chambonnièrea, E. Taranchonb, J-Y Scoazeca, MD, P.Hainautb, PhD

a Edouard Herriot Hospital, Lyon, France, bInternational Agency for Research on Cancer, Lyon, France.

AIM Adenocarcinomas of the esophagus (ADCE) and adenocarcinomas of the cardia (ADCC) are often grouped into a single pathological entity. Using strict criteria to distinguish between these lesions, we have investigated differences in TP53 mutations, MDM2 amplification and cytokeratin (CK) expression. We also report on alterations of beta catenin end E-cadherin molecules in ADCE. METHODS DNA was extracted from tumor areas of paraffin-embedded sections in 28 ADCC and 35 ADCE. TP53 mutations were detected by TTGE and identified by sequencing. MDM2 amplification was assessed by differential PCR. Expression of CKs 7, 13 and 20 was examined by immunohistochemistry (IHC). In ADCE, beta-catenin and E-cadherin expression was studied by IHC and beta-catenin gene mutations in exon 3 were screened. RESULTS ADCC and ADCE differed in the prevalence of TP53 mutations (31% versus 50%) and of MDM2 amplification (19% versus 4%) and in the pattern of CKs expression. Abnormal expression of E-cadherin and beta catenin was often correlated and was observed in 70-80% of ADCE. Mutation in beta-catenin (exon 3) was detected in 10% of the cases, and was inversely correlated with TP53 mutation. CONCLUSION ADCE and ADCC differ in the prevalence of TP53 mutations, MDM2 amplifications and in the patterns of cytokeratin expression, supporting the notion that ADCC and ADCE are distinct pathological entities. Moreover, adhesion molecules are frequently altered in ADCE, and mutations of beta-cqtenin may represent an alternative to TP53 mutations in esophageal carcinogenesis

KEY WORDS: cardia, esophagus, adenocarcinoma, beta-catenin cytokeratin.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Diagnostic Markers.