Association of HER1 amplification with poor prognosis in well differentiated gastric carcinomas.
OBJECTIVE
The pattern of E-cadherin expression and the HER1/HER2 status were studied in European patients with gastric carcinomas in relation with their differentiation and prognosis.


METHODS
82 gastric carcinomas (five papillary, 52 tubular, 19 poorly cohesive and six mixed according to WHO classification) were investigated for E-cadherin distribution (normal: restricted to the membrane; abnormal: absent or cytoplasmic expression), HER1 and HER2 expression using HercepTest and amplification using fluorescent in situ hybridisation. Statistical analysis assessed the association between the markers and their correlation with clinicopathological parameters and follow-up information.


RESULTS
Abnormal E-cadherin distribution was found in 34 of the 82 gastric carcinomas (41%) (18/25 poorly cohesive or mixed (72%); 16/57 papillary or tubular type (28%)). HER1 overexpression (3+) and equivocal expression (2+) were found in five carcinomas (6%; four tubular and one poorly cohesive) and eight carcinomas (10%; six tubular and two poorly cohesive), respectively. HER2 overexpression (3+) and equivocal expression (2+) were found in seven carcinomas (8%; five papillary and two tubular) and three carcinomas (4%; three tubular), respectively. Amplification of HER1 or HER2 was detected in 14 gastric carcinomas (five papillary and nine tubular). All of them showed a normal E-cadherin distribution. In the univariate analysis, only HER1 amplification had a prognostic impact, while HER2 amplification and E-cadherin expression/distribution were not per se prognostically relevant.


CONCLUSIONS
E-cadherin immunostaining and HER1 in situ hybridisation define a group of well differentiated gastric carcinomas with poor prognosis eligible for an aggressive therapeutic approach.
EA Biometadys, Université de Nantes, , Nantes, France.
Christine
C
Kandel
François
F
Leclair
Chantal
C
Bou-Hanna
Christian L
CL
Laboisse
Jean-François
JF
Mosnier
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D015820:Cadherins; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human
CERB 2; EGFR; Gastric Cancer; Histopathology; In Situ Hybridisation