Back to Clinical Case Reviews

Assessing HER2 IHC with edge artifacts

Case contributed by Gary Tozbikian, MD

The importance of reporting discrete HER2 IHC scores

Gary Tozbikian

MD

Case details

Age
48
Gender
Female

Tumor grade
3
Primary/metastatic breast cancer
Primary
Type of breast cancer
Invasive breast carcinoma of no special type (ductal)
Hormone receptor status
ER: Positive (90%, strong intensity)
PR: Positive (40%, moderate intensity)
HER2 by IHC
Equivocal (2+)
HER2 by FISH:
Negative (not amplified)
HER2/CEP17 ratio = 1.3, HER2/cell = 3.4
Pre-analytic variables and technical issues
None
Specimen type in primary setting:
Core needle biopsy

In this case, the HER2 IHC of a core needle biopsy specimen from an invasive breast carcinoma showed signs of edge artifact. Initial HER2 IHC was 2+, FISH negative. However, due to the presence of the artifact, repeat testing was performed. Repeat testing confirmed a HER2 IHC score of 2+ and negative FISH. This case will highlight the importance of avoiding HER2 IHC interpretation in areas with edge artifacts, and if extensive in amount to repeat testing if possible.* Core needle biopsy specimens in particular are prone to certain artifacts such as edge artifact and can make interpretation of these cases challenging.¹

Case summary

A core needle biopsy was performed on a 48-year-old female with a history of primary invasive breast carcinoma. HER2 IHC and FISH testing performed at an outside institution, revealed an IHC score of 2+ and negative FISH. However, it was observed that there was a significant edge artifact present on the sample.

The case was sent for consultation, and due to the presence of this significant edge artifact, HER2 IHC and FISH tests were repeated.

What is edge artifact?

The term “edge artifact” is used to describe a staining pattern where there is focal strong staining present along the tissue edges or in regions where tissue is disrupted due to an unequal distribution of assay reagents.¹ Edge artifacts can be caused by inconsistent fixation, the tissue drying out or lifting around the edges.²

Edge artifacts should be ignored during assay interpretation to avoid false-positive results.¹ Tissue samples, particularly core needle biopsies, with significant edge artifact should be excluded from evaluation, and consideration should be given to repeating the test on a different sample.³

Figure 1. The initial HER2 IHC slide (IHC 2+, 5X).

View whole slide image

What does the HER2 IHC staining indicate?

In the original HER2 IHC slide (Figure 1), most tumor cells show complete, circumferential membrane staining, ranging from moderate to strong intensity. However, there is a considerable edge artifact present in the core biopsy, with an appreciable variation in staining; where staining is highly concentrated at the peripheral edges of the tissue and diminishing in intensity towards the center of the tissue.

Figure 2. The repeat HER2 IHC slide (IHC 2+, 5X).

View whole slide image

Repeat HER2 IHC testing (Figure 2) did not display the edge artifact shown previously, and instead shows a staining pattern that is consistent with HER2 IHC 2+, with most of the tumor cells showing complete, circumferential membranous staining with a weak-to-moderate intensity. Reflex HER2 FISH was negative.

Discussion

It is important to be aware of artifacts that may hinder HER2 IHC interpretation, and can suggest problems with specimen processing and indicate poor quality staining.^1,3 It is recommended to avoid interpreting HER2 IHC in cases with extensive edge artifacts.⁴ In such cases, repeat testing on a different block or specimen may be helpful.³ Certain sample types such as core needle biopsies are particularly prone to edge artifacts, so it is important to be mindful when evaluating these specimens.¹

Considerations:

“Edge artifact” is the presence of focal strong staining along the tissue edges, and is common in core needle biopsy specimens¹

Tissue samples with significant edge artifact should be excluded from evaluation, and consideration should be given to repeating the test on a different sample³

More guidance on how to approach similar challenging breast cancer cases can be found in the e-learning series titled Interpreting HER2 in breast cancer: A full spectrum of possibilities, found in the Breast Tumors Resources.

*These practice considerations represent the opinions of the Breast Pathology Faculty. Members of the Breast Pathology Faculty have been contracted as paid advisors through Daiichi Sankyo and AstraZeneca and have received compensation for their time.

CEP17, chromosome enumeration probe 17; ER, estrogen receptor; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; PR, progesterone receptor.

1. Hicks DG and Schiffhauer L. Laboratory Medicine 2011;42(8):459-467. 2. VENTANA anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. Roche. 2022. 3. Wolff AC, et al. J Clin Oncol 2013;31(31):3997-4013. 4. Wolff AC, et al. J Clin Oncol. 2007;25(1):118-145.

Did you find this content useful?
Help us get it right next time by liking this article

Explore more Clinical Case Reviews

View all

In this series of articles, the Pathology Faculty share their experience with complex clinical cases and highlight practices that help to aid consistency in HER2 IHC scoring.

Assessing HER2 IHC with cytoplasmic staining

In this case, the HER2 IHC on a segmental mastectomy specimen from a primary invasive ductal carcinoma showed an unusual cytoplasmic staining pattern.

by Savitri Krishnamurthy, MD

The importance of reporting discrete HER2 IHC scores

In this case, the patient presented with primary breast cancer classified as HER2-negative.

by Marilyn Bui, MD, PhD

Interpreting HER2 IHC with an extensive in situ component

In this case, there was an extensive in situ component present along with the invasive carcinoma, and HER2 IHC scores were discordant between the two.

by Hannah Wen, MD, PhD

Assessing HER2 IHC with edge artifacts

Gary Tozbikian

MD

Case details

Age

Gender

Tumor grade

Primary/metastatic breast cancer

Type of breast cancer

Hormone receptor status

HER2 by IHC

HER2 by FISH:

Pre-analytic variables and technical issues

Specimen type in primary setting:

Case summary

What is edge artifact?

Figure 1. The initial HER2 IHC slide (IHC 2+, 5X).

What does the HER2 IHC staining indicate?

Figure 2. The repeat HER2 IHC slide (IHC 2+, 5X).

Discussion

Considerations:

Explore more Clinical Case Reviews

Assessing HER2 IHC with cytoplasmic staining

In this case, the HER2 IHC on a segmental mastectomy specimen from a primary invasive ductal carcinoma showed an unusual cytoplasmic staining pattern.

The importance of reporting discrete HER2 IHC scores

In this case, the patient presented with primary breast cancer classified as HER2-negative.

Interpreting HER2 IHC with an extensive in situ component

In this case, there was an extensive in situ component present along with the invasive carcinoma, and HER2 IHC scores were discordant between the two.

Quick Links

Breast Cancer Links

Gastric Cancer Links

About Us

Legal

What is a Daiichi Sankyo Company or AstraZeneca authorized person?

Assessing HER2 IHC with edge artifacts

Gary Tozbikian

MD

Case details

Patient information

Age

Gender

Case information

Tumor grade

Primary/metastatic breast cancer

Type of breast cancer

Hormone receptor status

HER2 by IHC

HER2 by FISH:

Pre-analytic variables and technical issues

Specimen type in primary setting:

Case summary

What is edge artifact?

Figure 1. The initial HER2 IHC slide (IHC 2+, 5X).

What does the HER2 IHC staining indicate?

Figure 2. The repeat HER2 IHC slide (IHC 2+, 5X).

Discussion

Considerations:

Explore more Clinical Case Reviews

Assessing HER2 IHC with cytoplasmic staining

In this case, the HER2 IHC on a segmental mastectomy specimen from a primary invasive ductal carcinoma showed an unusual cytoplasmic staining pattern.

The importance of reporting discrete HER2 IHC scores

In this case, the patient presented with primary breast cancer classified as HER2-negative.

Interpreting HER2 IHC with an extensive in situ component

In this case, there was an extensive in situ component present along with the invasive carcinoma, and HER2 IHC scores were discordant between the two.

Quick Links

Breast Cancer Links

Gastric Cancer Links

About Us

Legal

What is a Daiichi Sankyo Company or AstraZeneca authorized person?