title: E-cadherin expression in sporadic gastric cancer from Mexico: exon 8 and 9 deletions are infrequent events associated with poor survival.
abstract: Aberrant expression and mutation of E-cadherin is frequent in gastric carcinoma (GC) especially of the diffuse type. The frequency of CDH1 (gene encoding E-cadherin) mutation in populations with high incidence of diffuse GC and its prognostic significance is unknown. One hundred seventy-seven gastrectomies from Mexican mestizo patients with intestinal (53), mixed (55), or diffuse (69) GC were included. In addition, 101 endoscopic biopsies from patients with GC not subjected to surgery were analyzed. Immunohistochemistry against wild-type E-cadherin (clone 36) and against 2 mutation-specific antibodies (MSA) recognizing mutant CDH1 lacking exon-8 (del 8) or exon-9 (del 9) were performed. Staining was correlated with histotype, tumor node metastasis stage, and follow-up. Abnormal or absent E-cadherin expression (clone 36) was identified in 84% GC, predominantly in diffuse or mixed tumors (P = 0.004) in advanced stages (P = 0.003). No survival differences at 1 and 2 years were observed among patients showing normal, abnormal, or absent wild type E-cadherin expression. Overall reactivity with the MSA was observed in 10 (5.6%) patients who were treated with surgery. In 140 patients, dead from the disease or alive with the disease, the survival at 1 and 2 years was 37% versus 17% and 14% versus 0 for patients without and with del 8/9 positivity, respectively (log rank P = 0.01). Biopsies from patients with inoperable-GC (101) rendered 5 (4.95%) with del 8 or 9 immunoreactivity. Abnormal E-cadherin expression is frequent in GC. However, exon 8 or 9 deletions were observed in only 5.3% tumors in this series from Mexico, at a lower rate than previously published, but associated with a worse prognosis.
authors.affiliation: Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. agamboad@quetzal.innsz.mx
authors.forename: Armando
authors.initials: A
authors.lastname: Gamboa-Dominguez
authors.forename: Claudia
authors.initials: C
authors.lastname: Dominguez-Fonseca
authors.forename: Yanin
authors.initials: Y
authors.lastname: Chavarri-Guerra
authors.forename: Roberto
authors.initials: R
authors.lastname: Vargas
authors.forename: Edgardo
authors.initials: E
authors.lastname: Reyes-Gutierrez
authors.forename: Dan
authors.initials: D
authors.lastname: Green
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Birgit
authors.initials: B
authors.lastname: Luber
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Becker
authors.forename: Ingrid
authors.initials: I
authors.lastname: Becker
authors.forename: Heinz
authors.initials: H
authors.lastname: Höfler
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D002237:Carbohydrate Dehydrogenases / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008800:Mexico; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality*; D016019:Survival Analysis
chemical_list: D015820:Cadherins; D002237:Carbohydrate Dehydrogenases; C019859:cellobiose-quinone oxidoreductase