Dual gain of HER2 and EGFR gene copy numbers impacts the prognosis of carcinoma ex pleomorphic adenoma.
We investigated the potential roles of HER2 and EGFR and evaluated their prognostic significance in carcinoma ex pleomorphic adenoma (CXPA). We analyzed HER2 and EGFR overexpression status using immunohistochemistry (IHC) and gene copy number gain by chromogenic in situ hybridization (CISH) in 50 cases of CXPA (40 ductal-type and 10 myoepithelial-type CXPAs). Salivary duct carcinoma was the most common histologic subtype of malignant component (n = 21). Immunohistochemistry positivity and chromogenic in situ hybridization positivity were closely correlated in both HER2 and EGFR. HER2 CISH positivity (mostly gene amplification) and EGFR CISH positivity (mostly gene high polysomy) were present in 19 (40%) and 21 (44%) cases, respectively, and were each significantly correlated with poor outcome (P = .0009 and P = .0032, respectively). Dual gain of HER2 and EGFR gene copy numbers was present in 11 cases (23%) and was the most aggressive genotype. HER2 CISH positivity was more frequently present in ductal-type CXPAs (47%) than in myoepithelial-type CXPAs (10%), whereas the prevalence of EGFR CISH positivity was similar in both histologic subtypes (42% and 50%, respectively). Our results suggest that HER2 and EGFR gene copy number gains may play an important role in the progression of CXPA, in particular ductal-type CXPAs. HER2 CISH-positive/EGFR CISH-positive tumors may be the most aggressive subgroup in CXPA. The molecular subclassification of CXPA based on the HER2 and EGFR status may be helpful for prognostic prediction and decisions regarding the choice of therapeutic strategy.
Department of Anatomic Pathology, Graduate of School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
Toshimitsu
T
Nishijima
Department of Anatomic Pathology, Graduate of School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
Hidetaka
H
Yamamoto
Department of Otorhinolaryngology, Hamanomachi Hospital, Fukuoka 810-8539, Japan.
Takafumi
T
Nakano
Department of Otorhinolaryngology, Graduate of School of Medical Science, Kyushu University, Fukuoka 821-8582, Japan.
Torahiko
T
Nakashima
Department of Pathology, National Kyushu Cancer Center, Fukuoka 811-1347, Japan.
Ken-ichi
K
Taguchi
Department of Head and Neck Surgery, National Kyushu Cancer Center, Fukuoka 811-1347, Japan.
Muneyuki
M
Masuda
Department of Pathology, Hamanomachi Hospital, Fukuoka 810-8539, Japan.
Jun-ichi
J
Motoshita
Department of Otorhinolaryngology, Graduate of School of Medical Science, Kyushu University, Fukuoka 821-8582, Japan.
Shizuo
S
Komune
Department of Anatomic Pathology, Graduate of School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: oda@surgpath.med.kyushu-u.ac.jp.
Yoshinao
Y
Oda
D008949:Adenoma, Pleomorphic / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D056915:DNA Copy Number Variations; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology
D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human
Carcinoma ex pleomorphic adenoma; Chromogenic in situ hybridization; EGFR; HER2; Salivary gland tumor