PMID- 31192864
OWN - NLM
STAT- MEDLINE
DCOM- 20200409
LR  - 20200409
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 43
IP  - 9
DP  - 2019 Sep
TI  - Estrogen Receptor-positive Ductal Carcinoma In Situ Frequently Overexpresses HER2 
      Protein Without Gene Amplification.
PG  - 1221-1228
LID - 10.1097/PAS.0000000000001300 [doi]
AB  - Overexpression of human epidermal growth factor receptor 2 (HER2) protein is well 
      known to be more frequent in ductal carcinoma in situ (DCIS) than in invasive 
      ductal carcinoma (IDC). However, the reasons for this difference are poorly 
      understood. On the basis of the high frequency of estrogen receptor-positive 
      (ER+) and HER2-positive (HER2+) DCIS, we hypothesized that this tumor type 
      overexpresses HER2 protein without gene amplification and retrospectively 
      investigated the HER2/neu gene status of 71 ER(+)HER2(+) DCIS, surgically removed 
      during the 2007 to 2017 period, employing fluorescence in situ hybridization 
      (FISH). To compare HER2 protein expressions between in situ and invasive 
      components of individual tumors, 86 pT1mi/1a IDC with predominantly in situ 
      disease were also examined. Furthermore, for comparison of FISH status between in 
      situ and coexisting invasive components, another patient cohort, 78 FISH-positive 
      IDC cases, were employed. To elucidate biological differences among DCIS with 
      various combinations of ER and HER2 protein expressions, we also analyzed public 
      microarray data of mRNA. HER2 gene amplification was observed in 35% of ER(+) and 
      HER2 protein-overexpressing specimens, significantly lower than the 94% in 
      ER-negative (ER-) and HER2 protein-overexpressing specimens (P<0.001). HER2 
      protein expression was decreased in the invasive component as compared with 
      coexisting in situ portions in 40% of individual tumors, whereas the FISH status 
      of these 2 components was well preserved. Moreover, ER(+) and HER2 
      protein-overexpressing DCIS showed significantly higher hypoxia-inducible 
      factor-1alpha protein expression than the ER(+) and HER2 protein-nonoverexpressing 
      tumors (P=0.016). We revealed that ER(+) and HER2 protein-overexpressing DCIS, 
      especially ER-high tumors, frequently overexpress HER2 protein without gene 
      amplification. Our data may provide novel insights for understanding the biology 
      of DCIS.
FAU - Horimoto, Yoshiya
AU  - Horimoto Y
AD  - Departments of Breast Oncology.
AD  - Pathology and Oncology.
FAU - Terao, Takako
AU  - Terao T
AD  - Human Pathology, Juntendo University School of Medicine.
FAU - Tsutsumi, Yuko
AU  - Tsutsumi Y
AD  - Human Pathology, Juntendo University School of Medicine.
FAU - Tanabe, Masahiko
AU  - Tanabe M
AD  - Department of Breast and Endocrine Surgery, The University of Tokyo Hospital.
FAU - Mogushi, Kaoru
AU  - Mogushi K
AD  - Intractable Disease Research Center, Graduate School of Medicine, Juntendo 
      University, Tokyo, Japan.
FAU - Hlaing, May Thinzar
AU  - Hlaing MT
AD  - Pathology and Oncology.
FAU - Sasaki, Ritsuko
AU  - Sasaki R
AD  - Departments of Breast Oncology.
FAU - Saeki, Harumi
AU  - Saeki H
AD  - Pathology and Oncology.
FAU - Okazaki, Misato
AU  - Okazaki M
AD  - Departments of Breast Oncology.
FAU - Sonoue, Hiroshi
AU  - Sonoue H
AD  - Human Pathology, Juntendo University School of Medicine.
FAU - Arakawa, Atsushi
AU  - Arakawa A
AD  - Human Pathology, Juntendo University School of Medicine.
FAU - Saito, Mitsue
AU  - Saito M
AD  - Departments of Breast Oncology.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Breast Neoplasms/genetics/*metabolism/pathology
MH  - Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology
MH  - Female
MH  - Gene Amplification
MH  - Genes, erbB-2
MH  - Humans
MH  - Middle Aged
MH  - Receptor, ErbB-2/*biosynthesis
MH  - Receptors, Estrogen/metabolism
EDAT- 2019/06/14 06:00
MHDA- 2020/04/10 06:00
CRDT- 2019/06/14 06:00
PHST- 2019/06/14 06:00 [pubmed]
PHST- 2020/04/10 06:00 [medline]
PHST- 2019/06/14 06:00 [entrez]
AID - 10.1097/PAS.0000000000001300 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2019 Sep;43(9):1221-1228. doi: 10.1097/PAS.0000000000001300.