Human epithelial growth factor receptor 2 (HER2) status in primary and metastatic esophagogastric junction adenocarcinomas.
Differences in human epithelial growth factor receptor 2 dysregulation in primary solid tumors and metastases may (at least partially) explain human epithelial growth factor receptor 2-targeted therapeutic inconsistencies. Human epithelial growth factor receptor 2 status was tested in a series of 47 radically treated consecutive esophagogastric junction adenocarcinomas (male/female, 38/9; mean age, 67.9 years) in both primary cancers and paired synchronous nodal metastases. None of the patients received neoadjuvant therapy. For each case, 2 nonadjacent tissue samples from primary esophagogastric junction adenocarcinoma and 2 different metastatic nodes were considered (188 tissue samples in all). Human epithelial growth factor receptor 2 status was assessed by immunohistochemistry (PATHWAY-HER2/neu [4B5]; Ventana Medical Systems, Milan, Italy) and dual chromogenic in situ hybridization (duoCISH; DAKO, Glostrup, Denmark). Immunohistochemistry staining scores were nil in 22 tumors (47%), 1 (21%) in 10, 2 (13%) in 6, and 3 (19%) in 9. Human epithelial growth factor receptor 2 gene amplification (25.5%) was associated with more differentiated phenotype (Fisher exact test, P = .039) and advanced tumor stage (Fisher exact test, P = .015). Significant agreement was observed between human epithelial growth factor receptor 2 protein expression (immunohistochemistry) and human epithelial growth factor receptor 2 gene's amplification (chromogenic in situ hybridization) (κ = 0.84, P < .001). Both immunohistochemistry and chromogenic in situ hybridization documented an excellent intratumor agreement in human epithelial growth factor receptor 2 status (κ = 0.75, P < .001; κ = 0.88, P < .001, respectively). Human epithelial growth factor receptor 2 status was comparable in primary versus metastatic nodal cancers by both immunohistochemistry and chromogenic in situ hybridization (Cohen Φ, both P < .001). In esophagogastric junction adenocarcinomas, human epithelial growth factor receptor 2 status (as assessed by immunohistochemistry and/or chromogenic in situ hybridization) is virtually unaffected by intratumor variability; it is consistent with findings in nodal metastases, and it reliably identifies patients with esophagogastric junction adenocarcinoma eligible for anti-human epithelial growth factor receptor 2 therapy.
Department of Medical Diagnostic Sciences and Special Therapies (Pathology and Cytopathology Unit), University of Padova, 35100 Padova, Italy.
Matteo
M
Fassan
Kathrin
K
Ludwig
Marco
M
Pizzi
Carlo
C
Castoro
Vincenza
V
Guzzardo
Mariangela
M
Balistreri
Giovanni
G
Zaninotto
Alberto
A
Ruol
Luciano
L
Giacomelli
Ermanno
E
Ancona
Massimo
M
Rugge
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004943:Esophagogastric Junction / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human