Template:Immunohistochemistry evaluation of invasive breast cancer: Difference between revisions

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HER2 can also be evaluated by fluorescence ''in situ'' hybridization (FISH), either initially or in case of borderline/equivocal immunohistochemistry.<ref name=HER2-FISH>Mikael Häggström, MD. Adapted from: {{cite journal| author=Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS | display-authors=etal| title=Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. | journal=J Clin Oncol | year= 2018 | volume= 36 | issue= 20 | pages= 2105-2122 | pmid=29846122 | doi=10.1200/JCO.2018.77.8738 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29846122  }}</ref> It usually uses ''chromosome enumeration probe 17'' (CEP17) to count the amount of chromosomes, the HER2/CEP17 ratio reflects any amplification of HER2 as compared to the number of chromosomes.
HER2 can also be evaluated by fluorescence ''in situ'' hybridization (FISH), either initially or in case of borderline/equivocal immunohistochemistry.<ref name=HER2-FISH>Mikael Häggström, MD. Adapted from: {{cite journal| author=Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS | display-authors=etal| title=Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. | journal=J Clin Oncol | year= 2018 | volume= 36 | issue= 20 | pages= 2105-2122 | pmid=29846122 | doi=10.1200/JCO.2018.77.8738 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29846122  }}</ref> It usually uses ''chromosome enumeration probe 17'' (CEP17) to count the amount of chromosomes, the HER2/CEP17 ratio reflects any amplification of HER2 as compared to the number of chromosomes.
[[File:HER2 FISH algorithm.svg|thumb|400px|center|Algorithm for HER2 on FISH.<ref name=HER2-FISH/>]]
{| class="wikitable" align=center
|+ Classification of HER2 by fluorescence ''in situ'' hybridization (FISH)<ref name=HER2fish>Mikael Häggström, MD. Reference: {{cite journal| author=Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS | display-authors=etal| title=Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. | journal=J Clin Oncol | year= 2018 | volume= 36 | issue= 20 | pages= 2105-2122 | pmid=29846122 | doi=10.1200/JCO.2018.77.8738 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29846122  }}</ref>
|-
|rowspan=2 colspan=2| 
! colspan="2" | HER2/CEP17 ratio
|-
! ≥2.0
! <2.0
|-
! rowspan="2" | Average HER2 copy number per cell
! ≥4.0
| HER2 positive
| Additional work-up required<ref name=HER2fish group=note>If additional work-up is required by FISH study, see source article for detailed algorithms:<br>{{cite journal| author=Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS | display-authors=etal| title=Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. | journal=J Clin Oncol | year= 2018 | volume= 36 | issue= 20 | pages= 2105-2122 | pmid=29846122 | doi=10.1200/JCO.2018.77.8738 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29846122  }}
|-
! <4.0
| Additional work-up required<ref name=HER2fish group=note/>
| HER2 negative
|}


===Biomarker retesting===
===Biomarker retesting===

Revision as of 12:31, 5 October 2022

Immunohistochemistry

Ki-67 index

File:Positive immunohistochemistry of KI-67 in invasive breast cancer.jpg
Ki-67 in an invasive breast cancer: cancer nuclei are stained (brown). There is tumor cell positivity in 70% of the cells (Ki-67 labelling index = 70%).
File:Counting Ki-67 index in immunohistochemistry.jpg
To count as Ki-67 positive, a nucleus should:
- Not be located in stroma.
- Be at least half within the field of view.
- Be large enough.
Otherwise, even weakly positive nuclei count as positive.

Ki-67 index is mainly relevant in those with stage T1-T2, N0-N1, to determine if chemotherapy is needed (if Ki67 is >30% rather than <5%).[1]

Ki-67 index is most feasibly quantified by a hot spot method,[note 1] Hot spots are areas in which Ki-67 staining is particularly higher relative to the adjacent tumor areas.[2] Usually, the invasive edge of a tumor is a hot spot.[2] When a tumor had several hot spots, the “hottest” spot is selected.[2] Aim to count at least 500 cells in each case, but this is not always possible in cases with low tumor cell density and small tumor size.[2] Also aim to include at least three high-power (×40 objective) fields. Count a nucleus as “positive” if there is any definite brown staining in the nucleus of an invasive breast cancer cell, above the surrounding background in the cytoplasm and extracellular matrix.[3] If a comparisons must be made between core biopsies and sections from an excision, evaluation of the latter should be across the whole tumor.[1] Only nuclear staining counts. Staining intensity of a positive nucleus is not relevant.[1]

HER2

Immunohistochemistry
Score[4][5] Pattern[6] Status[4][5]
0 Either:[6]
  • No staining observed.
  • Incomplete membrane staining that is faint or barely perceptible and within ≤10% of the invasive tumor cells
 HER2 negative
(not present)
1+ Incomplete membrane staining that is faint or barely perceptible and within >10% of the invasive tumor cells.[6]
2+ Weak to moderate complete membrane staining observed in >10% of tumor cells.[6] Borderline/Equivocal
3+ Circumferential membrane staining that is complete, intense, and in >10% of tumor cells.[6] HER2 positive

Micrographs showing each score:[7]

  • 0
    0
  • 1+
    1+
  • 2+
    2+
  • 3+
    3+

HER2 can also be evaluated by fluorescence in situ hybridization (FISH), either initially or in case of borderline/equivocal immunohistochemistry.[8] It usually uses chromosome enumeration probe 17 (CEP17) to count the amount of chromosomes, the HER2/CEP17 ratio reflects any amplification of HER2 as compared to the number of chromosomes.

Classification of HER2 by fluorescence in situ hybridization (FISH)[9]
HER2/CEP17 ratio
≥2.0 <2.0
Average HER2 copy number per cell ≥4.0 HER2 positive Additional work-up requiredCite error: Closing </ref> missing for <ref> tag

In breast cancer metastases, retest estrogen and progesterone receptors, and HER2 in the following circumstances:[10]

  • If the status of the primary tumor is unknown or negative for ER/PR and/or HER2
  • If the primary tumor is heterogeneous for ER/PR expression
  • If the metastatic progression is unusual for the tumor characteristics
  • If the relapse is unexpectedly early or late
  • If unusual metastasis location
  • If the initial test was performed more than 10 years ago
  • If the testing turnaround time are relatively short (to reduce potential delays in patient management by retesting)

Notes

  1. ↑ Besides from a hot spot method of Ki67 counting, there is also a IKWG global average method which is more comprehensive. However, the inter-observer difference between the hot spot method and the 'IKWG global average is not statistically significant, and has not shown any significant difference in clinical outcome (theoretically, the area of highest Ki-67 proliferative index is probably most likely to correlate with malignant transformation and risk of metastasis, making the hot spot both more straightforward and clinically relevant than a global average).
    - Reference and instructions for the     IKWG global average method: Dowsett, M.; Nielsen, T. O.; A'Hern, R.; Bartlett, J.; Coombes, R. C.; Cuzick, J.; Ellis, M.; Henry, N. L.; et al. (2011). "Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group ". JNCI Journal of the National Cancer Institute 103 (22): 1656–1664. doi:10.1093/jnci/djr393. ISSN 0027-8874. 

Main page

References

  1. ↑ 1.0 1.1 1.2 Dowsett, M.; Nielsen, T. O.; A'Hern, R.; Bartlett, J.; Coombes, R. C.; Cuzick, J.; Ellis, M.; Henry, N. L.; et al. (2011). "Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group ". JNCI Journal of the National Cancer Institute 103 (22): 1656–1664. doi:10.1093/jnci/djr393. ISSN 0027-8874. 
  2. ↑ 2.0 2.1 2.2 2.3 Coleman, William B.; Jang, Min Hye; Kim, Hyun Jung; Chung, Yul Ri; Lee, Yangkyu; Park, So Yeon (2017). "A comparison of Ki-67 counting methods in luminal Breast Cancer: The Average Method vs. the Hot Spot Method ". PLOS ONE 12 (2): e0172031. doi:10.1371/journal.pone.0172031. ISSN 1932-6203. 
  3. ↑ . Ki67-QC international working group: whole section scoring protocol (global method). International Ki67 in Breast Cancer Working Group (2018-11-29).
  4. ↑ 4.0 4.1 . IHC Tests (ImmunoHistoChemistry). Breastcancer.org. Last modified on October 23, 2015
  5. ↑ 5.0 5.1 "Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications ". Molecular Biology International 2014: 852748. 2014. doi:10.1155/2014/852748. PMID 25276427. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 2018 ASCO/CAP guidelines:
    - . Figure 1. Algorithm for evaluation of human epidermal growth factor receptor 2 (HER2) protein expression by immunohistochemistry (IHC) assay of the invasive component of a breast cancer specimen.. College of American Pathologists: Homepage. Retrieved on 2022-09-12.
    - Ahn S, Woo JW, Lee K, Park SY (2020). "HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation. ". J Pathol Transl Med 54 (1): 34-44. doi:10.4132/jptm.2019.11.03. PMID 31693827. PMC: 6986968. Archived from the original. . 
  7. ↑ Nitta H, Kelly BD, Padilla M, Wick N, Brunhoeber P, Bai I (2012). "A gene-protein assay for human epidermal growth factor receptor 2 (HER2): brightfield tricolor visualization of HER2 protein, the HER2 gene, and chromosome 17 centromere (CEN17) in formalin-fixed, paraffin-embedded breast cancer tissue sections. ". Diagn Pathol 7: 60. doi:10.1186/1746-1596-7-60. PMID 22647525. PMC: 3487810. Archived from the original. . 
    - "This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)"
  8. ↑ Mikael Häggström, MD. Adapted from: Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS (2018). "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 36 (20): 2105-2122. doi:10.1200/JCO.2018.77.8738. PMID 29846122. Archived from the original. . 
  9. ↑ Mikael Häggström, MD. Reference: Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS (2018). "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 36 (20): 2105-2122. doi:10.1200/JCO.2018.77.8738. PMID 29846122. Archived from the original. . 
  10. ↑ Penault-Llorca F, Coudry RA, Hanna WM, Osamura RY, Rüschoff J, Viale G (2013). "Experts' opinion: Recommendations for retesting breast cancer metastases for HER2 and hormone receptor status. ". Breast 22 (2): 200-202. doi:10.1016/j.breast.2012.12.004. PMID 23352656. Archived from the original. . 

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