HER2 intratumoral heterogeneity analyses by concurrent HER2 gene and protein assessment for the prognosis of HER2 negative invasive breast cancer patients.
HER2 gene-protein assay (GPA) is a new method for the simultaneous evaluation of HER2 immunohistochemistry (IHC) and HER2 dual in situ hybridization (DISH) on single tissue sections of breast cancer. We investigated the presence of HER2 gene and protein discrepancy and HER2-heterogeneity using HER2-GPA. HER2 status was analyzed for the correlation between the presence of HER2-heterogeneity and patient prognosis. Consecutive 280 invasive breast cancer were examined. Statuses of HER2 protein and gene were evaluated in whole tumor sections of HER2 GPA slides. HER2 protein and gene combination patterns were classified to six phenotypic and genotypic types for each case, as well as at individual cell levels: (A) IHC and DISH positive; (B) IHC positive and DISH negative; (C) IHC equivocal and DISH positive; (D) IHC equivocal and DISH negative; (E) IHC negative and DISH positive; and (F) IHC and DISH negative. The presence of HER2-heterogeneity was determined by the existence of at least two of six types within one tumor. HER2-IHC positive patients had significantly worse survival than IHC negative patients and HER2-DISH positive patients had significantly worse survival than DISH negative patients. HER2 IHC negative and DISH positive patients had significantly worse recurrence-free survival than IHC and DISH negative patients. In the HER2 IHC and DISH negative group, the HER2 heterogeneous group had significantly worse survival than the nonheterogeneous group. Notably, among triple negative breast cancer (TNBC), the HER2 heterogeneous group had significantly worse survival than the nonheterogeneous group. Our study suggests that the presence of HER2-heterogeneity might be a prognostic factor in HER2 negative breast cancer patients, especially in TNBC.
Division of Breast Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, Japan.
Sasagu
S
Kurozumi
Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ, 85755, USA.
Mary
M
Padilla
Department of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan. mkurosumi@cancer-c.pref.saitama.jp.
Masafumi
M
Kurosumi
Division of Breast Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, Japan.
Hiroshi
H
Matsumoto
Division of Breast Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama, Japan.
Kenichi
K
Inoue
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi-city, Gunma, Japan.
Jun
J
Horiguchi
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi-city, Gunma, Japan.
Izumi
I
Takeyoshi
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi-city, Gunma, Japan.
Tetsunari
T
Oyama
Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ, 85755, USA.
Jim
J
Ranger-Moore
Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ, 85755, USA.
D Craig
DC
Allred
Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ, 85755, USA.
Eslie
E
Dennis
Ventana Medical Systems, Inc., 1910 East Innovation Park Drive, Tucson, AZ, 85755, USA.
Hiroaki
H
Nitta
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis
D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
Breast cancer; Gene-protein assay; HER2; Intratumoral heterogeneity; Trastuzumab