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HER-2 Immunohistochemistry (IHC), Breast With Reflex to FISH if 2+ by IHC

Test Number 483289
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CPT

88360. If reflex testing is performed, concomitant CPT codes/charges will apply.
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  • Updated on 04/14/2025

Test Details

Methodology

Immunohistochemistry (IHC)

Result Turnaround Time

4 - 5 days

Turnaround time is defined as the usual number of days from the date of pickup of a specimen for testing to when the result is released to the ordering provider. In some cases, additional time should be allowed for additional confirmatory or additional reflex tests. Testing schedules may vary.

Related Information

Use

Equivocal results by IHC should be reflexed to HER2 FISH to determine overall status. HER-2/neu overexpression is a predictor of response to certain breast cancer therapies, including targeted immunotherapies. A positive IHC result (3+) or an equivocal result with ISH amplification provides eligibility for trastuzumab (HERCEPTIN®) and trastuzumab emtansine (KADCYLA®) therapies. This test can also be used to qualify patients as HER2-low (1+ IHC or 2+/ISH-) or HER2-ultralow (any staining of the membrane in greater than 0 and less than or equal to 10% of invasive tumor cells) for fam-trastuzumab-deruxtecan-nxki (ENHERTU®) eligibility determination.

Tissues are evaluated by immunohistochemistry. Specimens demonstrating 2+ (moderate) staining for the HER-2/neu protein are evaluated for gene amplification status by FISH. In such cases, FISH provides a better indication of potential response to therapy.

Equivocal results by IHC should be reflexed to HER2 FISH to determine overall status. HER-2/neu overexpression is a predictor of response to certain breast cancer therapies, including targeted immunotherapies. A positive IHC result (3+) or an equivocal result with ISH amplification provides eligibility for trastuzumab (HERCEPTIN®) and trastuzumab emtansine (KADCYLA®) therapies. This test can also be used to qualify patients as HER2-low (1+ IHC or 2+/ISH-) or HER2-ultralow (any staining of the membrane in greater than 0 and less than or equal to 10% of invasive tumor cells) for fam-trastuzumab-deruxtecan-nxki (ENHERTU®) eligibility determination.

Special Instructions

Please direct any questions regarding this test to oncology customer service at 800-345-4363.

Limitations

Use of fixatives other than 10% neutral-buffered formalin or fixation times less than six hours or more than 72 hours may not yield reliable results. Decalcification procedures may negatively affect antigenicity and DNA quality.

Use of fixatives other than 10% neutral-buffered formalin or fixation times less than six hours or more than 48 hours may not yield equivalent or satisfactory results.

Use of fixatives other than 10% neutral-buffered formalin or fixation times less than six hours or more than 72 hours may not yield reliable results. Decalcification procedures may negatively affect antigenicity and DNA quality.

Specimen Requirements

Specimen

Formalin-fixed, paraffin-embedded (FFPE) tumor

Volume

One paraffin block or seven unstained, positively-charged tissue slides cut at 4 to 5 microns and dried for one hour at 60°C.

Container

Paraffin block transport pouch or slide mailer

Collection Instructions

Specimen should be fixed in 10% neutral-buffered formalin. Time from tissue acquisition to fixation should be as short as possible. Fixation time should be between six and 72 hours according to ASCO/CAP guidelines.

Specimen should be fixed in 10% neutral-buffered formalin. Fixation time should be between six and 72 hours according to ASCO/CAP guidelines; however, the package insert indicates optimum fixation time between 18 and 24 hours.

Specimen should be fixed in 10% neutral-buffered formalin. Time from tissue acquisition to fixation should be as short as possible. Fixation time should be between six and 72 hours according to ASCO/CAP guidelines.

Storage Instructions

Maintain specimen at room temperature.

Causes for Rejection

Tumor other than breast tumor

References

Modi S, Jacot W, Yamashita T, Petukhova MN, Agafonov SV, Itkin GP. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. PubMed 35665782

PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody [package insert]. Roche Diagnostics; Jan 29, 2025.

Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018 Jul 10;36(20):2105-2122. PubMed 29846122

 
Dybdal N, Lieberman G, Anderson S, et al. Determination of HER2 gene amplification by fluorescence in situ hybridization and concordance with the clinical trials immunohistochemical assay in women with metastatic breast cancer evaluated for treatment with trastuzumab. Breast Cancer Res Treat. 2005 Sep; 93(1):3-11.16184453
Mass RD, Press M, Anderson S, et al. Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab. Clin Breast Cancer. 2005 Aug; 6(3):240-246.16137435
Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018 Jul 10;36(20):2105-2122.29846122

Modi S, Jacot W, Yamashita T, Petukhova MN, Agafonov SV, Itkin GP. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. PubMed 35665782

PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody [package insert]. Roche Diagnostics; Jan 29, 2025.

Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018 Jul 10;36(20):2105-2122. PubMed 29846122

 

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
483289 HER-2 IHC With Reflex To FISH 480529 HER-2/neu (C-erbB-2) 18474-7
483289 HER-2 IHC With Reflex To FISH 480458 Scoring Guide 19147-8
483289 HER-2 IHC With Reflex To FISH 480382 Comment 77202-0
483289 HER-2 IHC With Reflex To FISH 480383 Fixation Time N/A
483289 HER-2 IHC With Reflex To FISH 480387 Fixative N/A
483289 HER-2 IHC With Reflex To FISH 480241 Director Review 72486-4
Order Code483289
Order Code NameHER-2 IHC With Reflex To FISH
Order Loinc
Result Code480529
Result Code NameHER-2/neu (C-erbB-2)
UofM
Result LOINC18474-7
Order Code483289
Order Code NameHER-2 IHC With Reflex To FISH
Order Loinc
Result Code480458
Result Code NameScoring Guide
UofM
Result LOINC19147-8
Order Code483289
Order Code NameHER-2 IHC With Reflex To FISH
Order Loinc
Result Code480382
Result Code NameComment
UofM
Result LOINC77202-0
Order Code483289
Order Code NameHER-2 IHC With Reflex To FISH
Order Loinc
Result Code480383
Result Code NameFixation Time
UofM
Result LOINCN/A
Order Code483289
Order Code NameHER-2 IHC With Reflex To FISH
Order Loinc
Result Code480387
Result Code NameFixative
UofM
Result LOINCN/A
Order Code483289
Order Code NameHER-2 IHC With Reflex To FISH
Order Loinc
Result Code480241
Result Code NameDirector Review
UofM
Result LOINC72486-4
Reflex Table for HER-2/neu (C-erbB-2)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 483297 HER-2/neu Gene Amplification 483298 HER-2/neu Gene Amplification 31150-6
Reflex 1
Order Code483297
Order NameHER-2/neu Gene Amplification
Result Code483298
Result NameHER-2/neu Gene Amplification
UofM
Result LOINC31150-6
Reflex Table for HER-2/neu (C-erbB-2)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 483297 HER-2/neu Gene Amplification 483299 HER-2/CEP17 Ratio 49683-6
Reflex 1
Order Code483297
Order NameHER-2/neu Gene Amplification
Result Code483299
Result NameHER-2/CEP17 Ratio
UofM
Result LOINC49683-6
Reflex Table for HER-2/neu (C-erbB-2)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 483297 HER-2/neu Gene Amplification 483328 Avg Num Her-2 signals/nucleus: 74860-8
Reflex 1
Order Code483297
Order NameHER-2/neu Gene Amplification
Result Code483328
Result NameAvg Num Her-2 signals/nucleus:
UofM
Result LOINC74860-8
Reflex Table for HER-2/neu (C-erbB-2)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 483297 HER-2/neu Gene Amplification 483329 Avg Num CEP17 probes/nucleus: 74861-6
Reflex 1
Order Code483297
Order NameHER-2/neu Gene Amplification
Result Code483329
Result NameAvg Num CEP17 probes/nucleus:
UofM
Result LOINC74861-6
Reflex Table for HER-2/neu (C-erbB-2)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 483297 HER-2/neu Gene Amplification 483332 Number of Tumor Cells Counted: 62361-1
Reflex 1
Order Code483297
Order NameHER-2/neu Gene Amplification
Result Code483332
Result NameNumber of Tumor Cells Counted:
UofM
Result LOINC62361-1
Reflex Table for HER-2/neu (C-erbB-2)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 483297 HER-2/neu Gene Amplification 483334 Number of Observers: N/A
Reflex 1
Order Code483297
Order NameHER-2/neu Gene Amplification
Result Code483334
Result NameNumber of Observers:
UofM
Result LOINCN/A
Reflex Table for HER-2/neu (C-erbB-2)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 483297 HER-2/neu Gene Amplification 483336 Scoring Criteria 19147-8
Reflex 1
Order Code483297
Order NameHER-2/neu Gene Amplification
Result Code483336
Result NameScoring Criteria
UofM
Result LOINC19147-8
Reflex Table for HER-2/neu (C-erbB-2)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 483297 HER-2/neu Gene Amplification 483003 Director Review N/A
Reflex 1
Order Code483297
Order NameHER-2/neu Gene Amplification
Result Code483003
Result NameDirector Review
UofM
Result LOINCN/A