Comparison of HER2 status between surgically resected specimens and matched biopsy specimens of gastric intestinal-type adenocarcinoma.
Author(s): Yoshida H, Yamamoto N, Taniguchi H, Oda I, Katai H, Kushima R, Tsuda H
Publication: Virchows Arch, 2014, Vol. 465, Page 145-54
PubMed ID: 24889042 PubMed Review Paper? No
Purpose of Paper
This paper compared human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) and fluorescent in situ hybridization (FISH) results in matched biopsy and resection specimens.
Conclusion of Paper
HER2 overexpression detected by IHC and HER2 amplification analyzed by FISH were observed in comparable percentages of surgically resected and biopsy specimens. Matched resection and biopsy specimens had concordant HER2 IHC scores in 57% of specimens and concordant FISH results in 72.7% of specimens. Discordance in IHC staining primarily arose from 40 specimens that were HER2 2+ or 3+ in the biopsy but HER2 0 or 1+ in the resection but a similar trend in discordance was not observed for FISH. Biopsy and resection specimens with HER2 3+ IHC staining showed FISH amplification in 94% and 89% of cases, respectively. Specimens with HER2 IHC staining of 0 or 1+ were found to have HER2 amplification by FISH in only 10% of resection specimens and 9% of biopsy specimens. Polysomy 17 occurred in 5.5% of resected specimens and 7.5% of biopsy specimens and was more common when the IHC HER2 scores was 2+ or 3+.
Studies
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Study Purpose
This study compared human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) and fluorescent in situ hybridization (FISH) results in matched biopsy and resection specimens. Two hundred and seven surgically resected intestinal-type gastric adenocarcinomas that had invaded the submucosal layer and 158 matched biopsy specimens were fixed in 10% formalin for 24 or 36 h and embedded in paraffin. Specimens were sectioned at 5µm for IHC and 4 µm for FISH analysis. IHC staining was graded as 0 (no staining in <10% of tumor cells), 1+ (faint staining in ≥10 % of tumor cells), 2+ (weak to moderate complete, basolateral, or lateral membranous staining in >10 % of tumor cells) or to 3+ (strong complete, basolateral, or lateral membranous staining in >10 % of tumor cells). HER2 was considered non-amplified when the ratio of HER2 to CEP17 FISH signals for 20 cells was less than 1.8, and considered amplified when greater than 2.2. In cases where the ratio of HER2 to CEP17 FISH signals in the first 20 cells was 1.8-2.2, an additional 20 cells were counted and a ratio of 2.0 or higher was considered positive. Cases where the CEP17 signal was greater than 3.0/cell were considered to be chromosome 17 polysomy.
Summary of Findings:
HER2 overexpression was observed in 17% (35 of 207) of surgically-resected specimens and 17% (26 of 158) of biopsy specimens. Gene amplification by FISH was observed in 31% (61 of 200) of surgically-resected specimens and in 32% (47 of 147) of biopsy specimens. Matched biopsy and resection specimens had concordant HER2 IHC staining in 57% (90 of 158) of specimens and concordant FISH results in 72.7% (104 of 143) of specimens. Discordance primarily arose from 40 specimens that were HER2 2+ or 3+ in the biopsy but HER2 0 or 1+ in the resection. The opposite (HER2 0 or 1+ in biopsy and 2+ or 3+ in the resection) was observed in only 10 specimens. A comparable number of the discordant specimens were HER2-amplified only in the biopsy but not resection specimens and HER2-amplified in the resection but not the biopsy specimen (20 versus 19). Of the specimens with HER2 3+ staining, HER2 was amplified by FISH in 94% (33 of 35) of resected specimens and 89% (23 of 26) of biopsy specimens. Specimens with HER2 IHC scores of 2+ showed HER2 amplification by FISH in 56% (14 of 25) of resected specimens and 38% (17 of 45) of biopsy specimens. Of the specimens with IHC staining scored as 0 or 1+, 10% (14 of 140) of resection specimens and 9% (7 of 76) of biopsy specimens were found to have HER2 amplification by FISH. Importantly, when cases positive for HER2 by FISH with HER2 IHC scores of 0 or 1+ were further investigated, 79% (11 of 14) of resected specimens and 86% (6 of 7) biopsy specimens were classified as low level amplification (2.0 to <3.0 HER2/CEP17). Polysomy 17 occurred in 5.5% (11 of 200) of resected specimens and 7.5% (11 of 147) of biopsy specimens and was more common in resection and biopsy specimens with IHC HER2 scores of 2+ or 3+ than those with scores of 0 or 1+ (15% versus 1.4%, P<0.0001 and 14% versus 1.3%, P=0.0037; respectively). FISH-negative polysomy 17 was found in 5 resection and 5 biopsy specimens.
Biospecimens
Preservative Types
- Formalin
Diagnoses:
- Neoplastic - Carcinoma
Platform:
Analyte Technology Platform Protein Immunohistochemistry DNA FISH Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Method of tissue acquisition Biopsy
Surgical resection
FISH Specific Technology platform IHC
Immunohistochemistry Specific Targeted peptide/protein HER2
FISH Specific Targeted nucleic acid HER2
CEP17