Immunohistochemical detection of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in formalin-fixed breast carcinoma cell block preparations: correlation of results to corresponding tissue block (needle core and excision) samples.
Author(s): Kinsella MD, Birdsong GG, Siddiqui MT, Cohen C, Hanley KZ
Publication: Diagn Cytopathol, 2013, Vol. 41, Page 192-8
PubMed ID: 22611048 PubMed Review Paper? No
Purpose of Paper
This paper compared immunohistochemical (IHC) status of estrogen receptor (ER, esr), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2/neu) and fluorescent in situ hybridization (FISH)-detected amplification of Her2 in formalin-fixed cell block and surgical specimens.
Conclusion of Paper
ER, PR, and Her2 status in cell block and surgical specimens were 92%, 78%, and 76% concordant; respectively. The cell block was collected at a metastasis and the surgical specimen at the primary location in all four cases of ER discrepancy, in nine of 11 cases of PR discrepancy, and in 11 of 13 cases of Her2 discrepancy. Interestingly, there was no trend in the discrepancies with the positive and negative results occurring at a similar frequency in the cell block and surgical specimens and when Her2 IHC status was equivocal in one specimen type and negative in the other, no Her2 amplification was found in either specimen by FISH.
Studies
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Study Purpose
This study compared ER, PR, and Her2 IHC status and Her2 amplification by FISH in formalin-fixed cell block and surgical specimens. Staining results were compared between CB (fine needle aspiration) specimens and matched surgical specimens (excision or CNB) from 50 patients with primary (9) or metastatic breast cancer (41). In all cases, the FNA was obtained first and immediately fixed for 6 h or more in 10% NBF. After initial diagnosis but before treatment, surgical specimens (19 CNB and 31 excision specimens) were fixed for at least 6 h in 10%NBF. CNB and CB specimens were fixed immediately and the surgical excision specimens were stored for up to 3 h before fixation. Her2 was considered amplified when the ratio of Her2 to CEP-17 was greater than 2.2 and was considered equivocal with a ratio of 1.8-2.2.
Summary of Findings:
The ER status was concordant between the CB and the surgical specimen in 46 of 50 cases (92%, P<0.0001). In all four discrepant cases, the CB was obtained from a metastasis and the surgical specimen from the primary tumor. Two of the four discordant cases were ER positive in the surgical specimen, but negative in the CB and the other two cases were ER negative in the surgical specimen but positive in the cell block.
PR status was concordant between the CB and the surgical specimens in 39 of 50 cases (78%, P=0.0021), with nine of the discrepant cases sampled at different sites (CB from metastasis and surgical from primary tumor). Of the discrepant cases, five were negative in the cell block and positive in the surgical specimen and six were positive in the cell block but negative in the surgical specimen.
Her2 status by a combination of FISH and IHC was concordant in 37 of 50 cases (72%, P=0.0020). Two cases of discrepancy were considered major (one positive, one negative) and 11 minor (positive or negative in one and equivocal in other). In both cases with a major discrepancy in findings and in 10 of 11 cases with a minor discrepancy, the CB was from a metastatic site. The major discrepancies observed included one case where the CB was positive and one where it was negative. Her2 did not show amplification in either specimen by FISH when the surgical specimen was positive but the CB was negative, but Her2 amplification was equivocal in both specimens when the CB was positive and the surgical specimen was negative. The minor discrepancies included one positive in CB and one positive in the surgical specimen where the matched specimen was equivocal and for both cases, Her2 amplification by FISH was positive in both specimens. The remaining 11 minor discrepancies included five cases that were negative in the surgical specimens but equivocal in the CB and six cases that were negative in the cell block but equivocal in the surgical specimens. Interestingly, in all 11 of these cases FISH was negative in the specimen judged equivocal by IHC.
Biospecimens
Preservative Types
- Formalin
Diagnoses:
- Neoplastic - Carcinoma
Platform:
Analyte Technology Platform DNA FISH Protein Immunohistochemistry Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Immunohistochemistry Specific Targeted peptide/protein Her2
ER
PR
Biospecimen Acquisition Method of tissue acquisition Core needle biopsy
Fine needle aspiration
Surgical resection
Biospecimen Acquisition Biospecimen location Primary tumor
Metastasis
FISH Specific Targeted nucleic acid Her2
CEP-17