Fluorescence in situ hybridization gene amplification analysis of EGFR and HER2 in patients with malignant salivary gland tumors treated with lapatinib.
BACKGROUND
Gene amplification status of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2) were analyzed and correlated with clinical outcome in patients with progressive malignant salivary glands tumors (MSGT) treated with the dual EGFR/Her2 tyrosine kinase inhibitor lapatinib.


METHODS
Fluorescence in situ hybridization (FISH) analysis for both EGFR and HER2 gene amplification was performed successfully in the archival tumor specimens of 20 patients with adenoid cystic carcinomas (ACC) and 17 patients with non-ACC, all treated with lapatinib.


RESULTS
For ACC, no EGFR or HER2 amplifications were detected. For non-ACC, no EGFR gene amplifications were detected but 3 patients (18%) were HER2 amplified and all had stained 3+ for both EGFR and HER2 by immunohistochemistry (IHC) in their archival specimens. Two of these patients had time-to-progression (TTP) durations of 8.3 months and 18.4 months, respectively. Interestingly, patients with low and high HER2/chromosome-specific centromeric enumeration probe (CEP) 17 ratio had a prolonged TTP than those with moderate ratios for both ACC and non-AAC subtypes.


CONCLUSIONS
HER2 to CEP17 FISH ratio may predict which patients with MSGT have an increased likelihood to benefit from lapatinib. The finding of HER2:CEP17 ratio as a predictive marker of efficacy to lapatinib warrants further investigation.
Vidal
Laura
L
Princess Margaret Hospital Phase II Consortium, Toronto, Canada.
Tsao
Ming S
MS
Pond
Gregory R
GR
Cohen
Ezra E W
EE
Cohen
Roger B
RB
Chen
Eric X
EX
Agulnik
Mark
M
Hotte
Sebastien
S
Winquist
Eric
E
Laurie
Scott
S
Hayes
D Neil
DN
Ho
James
J
Dancey
Janet
J
Siu
Lillian L
LL
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007262:Infusions, Intravenous; D000077341:Lapatinib; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases