PMID- 29923906
OWN - NLM
STAT- MEDLINE
DCOM- 20190828
LR  - 20190828
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 42
IP  - 9
DP  - 2018 Sep
TI  - Comparative Pathologic Analysis of Breast Cancers Classified as 
      HER2/neu-Amplified by FISH Using a Standard HER2/CEP17 Dual Probe and an 
      Alternative Chromosome 17 Control Probe.
PG  - 1208-1215
LID - 10.1097/PAS.0000000000001106 [doi]
AB  - At our institution, breast cancer cases that generate an equivocal HER2/neu 
      (HER2) result by fluorescence in situ hybridization (FISH) using the dual 
      HER2/chromosome enumeration probe (CEP17) are reflexed to an assay that utilizes 
      an alternative control probe (lissencephaly gene1 [LIS1] [17p13.3]/retinoic acid 
      receptor alpha [RARA] [17q21.2]). This study examines whether cancers that are 
      classified as HER2-amplified with an alternate probe are clinicopathologically 
      similar to those that are classified as such using the HER2/CEP17 probe. Reports 
      for 1201 breast cancers were reviewed, and clinicopathologic findings were 
      compared between HER2/CEP17-equivocal cases that became HER2-amplified using the 
      alternate probe (group A: n=48), HER2-amplified cases using the HER2/CEP17 probe 
      (group B: n=169), and HER2-nonamplified cases using the HER2/CEP17 probe (group 
      C: n=910). Of 1201 cases tested using the HER2/CEP17 probe, 169 (14%) were 
      HER2-amplified, 122 (10%) were equivocal, and 910 (76%) were nonamplified. 
      Additional testing with the alternative probe on the 122 equivocal cases 
      reclassified 48 (39%) of them to HER2-amplified, and such cases comprised 22% of 
      all HER2-amplified tumors. A higher proportion of tumors with HER2 copy number 
      between 5.0 and 5.9 became positive upon additional testing when compared with 
      those with a priori HER2 copy numbers between 4.0 and 4.9 (P=0.0362). Group A 
      cases, compared with group B cases, were more frequently positive for estrogen 
      receptor (97.91% vs. 72.18%, P<0.0001) and progesterone receptor (85.41% vs. 
      59.17%, P=0.0009). Most group A cases (71%) were HER2 equivocal (score 2+) by 
      immunohistochemistry, whereas most group B cases (60%) were positive (score 3+). 
      Groups A and B showed no significant differences regarding patient age, lymph 
      node status, tumor grade, histotype, and stage distribution. In summary, among 
      our HER2-amplified cohort of breast cancers, alternative probe-detected cases 
      were more frequently estrogen receptor and progesterone receptor positive than 
      HER2/CEP17-detected cases, and were more frequently discordant with HER2 
      immunohistochemistry results. These findings raise the possibility of underlying 
      biologic differences between these 2 groups, which warrants further study. 
      However, the tumors were largely comparable regarding all other clinicopathologic 
      variables. As it is unknown whether HER2-targeted therapy is truly beneficial in 
      this subgroup of patients, future clinical trials should specifically evaluate 
      this subset.
FAU - Zare, Somaye
AU  - Zare S
AD  - Department of Pathology, University of California San Diego, San Diego, CA.
FAU - Lin, Leo
AU  - Lin L
FAU - Alghamdi, Abrar G
AU  - Alghamdi AG
FAU - Daehne, Svenja
AU  - Daehne S
FAU - Roma, Andres A
AU  - Roma AA
FAU - Hasteh, Farnaz
AU  - Hasteh F
FAU - Dell'Aquila, Marie
AU  - Dell'Aquila M
FAU - Fadare, Oluwole
AU  - Fadare O
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
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  - Aged, 80 and over
MH  - Biomarkers, Tumor/*analysis/genetics
MH  - Breast Neoplasms/*genetics
MH  - Carcinoma/*genetics
MH  - Chromosomes, Human, Pair 17
MH  - Female
MH  - Gene Expression Profiling/methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Middle Aged
MH  - Receptor, ErbB-2/*analysis/genetics
MH  - Young Adult
EDAT- 2018/06/21 06:00
MHDA- 2019/08/29 06:00
CRDT- 2018/06/21 06:00
PHST- 2018/06/21 06:00 [pubmed]
PHST- 2019/08/29 06:00 [medline]
PHST- 2018/06/21 06:00 [entrez]
AID - 10.1097/PAS.0000000000001106 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2018 Sep;42(9):1208-1215. doi: 10.1097/PAS.0000000000001106.