PMID- 20216378
OWN - NLM
STAT- MEDLINE
DCOM- 20100415
LR  - 20220316
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 34
IP  - 4
DP  - 2010 Apr
TI  - Accurately assessing her-2/neu status in needle core biopsies of breast cancer 
      patients in the era of neoadjuvant therapy: emerging questions and considerations 
      addressed.
PG  - 575-81
LID - 10.1097/PAS.0b013e3181d65639 [doi]
AB  - BACKGROUND: Emerging data show that patients with operable, HER-2/neu 
      overexpressed/amplified breast carcinomas have significantly better responses 
      (more frequently obtaining pathologic complete response and greater percent 
      disease-free survival) when treated with trastuzumab (Herceptin) simultaneously 
      with neoadjuvant chemotherapy than with chemotherapy alone. With the increasing 
      use of neoadjuvant therapies, clinicians require information on biomarkers 
      including HER-2/neu status at the time of needle core biopsy. Concordance rates 
      between fluorescence in situ hybridization (FISH)-determined HER-2/neu status on 
      needle core biopsies and on subsequent excisional biopsies of the same tumor have 
      not been well studied. Moreover, the practice of automatically performing 
      ("reflexing") 2+ immunohistochemical (IHC) staining needle core biopsies for FISH 
      analysis on the same sample needs to be validated. In this study, we set out to 
      (1) determine the accuracy of HER-2/neu status as determined by FISH on needle 
      core biopsy material compared with FISH on the subsequent excisional biopsy of 
      the same tumor with special consideration of IHC 2+staining cases and (2) 
      determine the constancy of HER-2/neu status in pre-neoadjuvant and 
      post-neoadjuvant chemotherapy-treated tumor in the form of needle core biopsy and 
      excisional biopsy samples, respectively. DESIGN: 100 patients whose needle core 
      biopsies and subsequent excisional biopsy samples were pathologically evaluated 
      at our institution were studied. For each patient, unstained sections from both 
      specimens were prepared and used for IHC or FISH. IHC was carried out using the 
      HercepTest kit (DAKO, Carpinteria, CA). Parallel unstained slides were used to 
      carry out FISH (dual probe, Vysis). Statistical analyses were carried out on the 
      resulting data generated after interpretation. RESULTS: The concordance rate 
      between FISH results determined on the needle core biopsy and subsequent 
      excisional biopsy of the same tumor was 86% (kappa=0.56, P=2x10). If equivocal 
      FISH cases (> or =1.8 to < or =2.2 amplification ratio) in a needle core biopsy 
      or excisional biopsy specimen or both, were excluded, the concordance rate 
      increased to 95% (kappa coefficient=0.86, P=2x10). Fourteen of 100 (14%) cases 
      showed 2+ IHC staining in the needle core biopsy specimen with good concordance 
      of FISH-determined HER-2/neu status between the needle core biopsy and excisional 
      biopsy specimens (79% agreement and kappa=0.512, P=0.05). Nine, 3, and 2 cases of 
      the 14 cases were amplified, equivocal, and negative on the excisional biopsy 
      specimens, respectively. Of the 15 patients who received neoadjuvant 
      chemotherapy, 93% and 87% had no change in HER-2/neu status as determined by IHC 
      or FISH, respectively, in the excisional biopsy specimen when compared with that 
      determined on the prior core biopsy sample. CONCLUSIONS: Excellent overall 
      concordance was achieved between FISH-determined HER-2/neu status on the needle 
      core biopsy and that determined on the subsequent excisional biopsy of the same 
      tumor. These results suggest that intratumoral heterogeneity of HER-2/neu 
      assessed by FISH is not a significant confounding factor when analyzing smaller 
      sized samples. Furthermore, 79% of 2+IHC staining needle core biopsy cases showed 
      concordant FISH results in the needle core biopsy and subsequent excisional 
      biopsy specimens. Our results show good concordance, however, larger cohorts need 
      to be studied to verify this finding. HER-2/neu status remains unchanged in the 
      majority of cases when comparing pre-neoadjuvant and post-neoadjuvant 
      chemotherapy-treated specimens.
FAU - D'Alfonso, Timothy
AU  - D'Alfonso T
AD  - Department of Pathology and Laboratory Medicine-Starr, Weill Cornell Medical 
      Center, New York, NY 10065, USA.
FAU - Liu, Yi-Fang
AU  - Liu YF
FAU - Monni, Stefano
AU  - Monni S
FAU - Rosen, Paul Peter
AU  - Rosen PP
FAU - Shin, Sandra J
AU  - Shin SJ
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  - 0 (DNA, Neoplasm)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Biopsy, Needle
MH  - Breast Neoplasms/*diagnosis/genetics/metabolism/therapy
MH  - DNA, Neoplasm/analysis
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Neoadjuvant Therapy
MH  - Receptor, ErbB-2/genetics/*metabolism
MH  - Reproducibility of Results
EDAT- 2010/03/11 06:00
MHDA- 2010/04/16 06:00
CRDT- 2010/03/11 06:00
PHST- 2010/03/11 06:00 [entrez]
PHST- 2010/03/11 06:00 [pubmed]
PHST- 2010/04/16 06:00 [medline]
AID - 10.1097/PAS.0b013e3181d65639 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2010 Apr;34(4):575-81. doi: 10.1097/PAS.0b013e3181d65639.