Template:Immunohistochemistry evaluation of invasive breast cancer

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Immunohistochemistry

Ki-67 index

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%).
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]

Biomarker retesting

((If the previous biopsy was negative for ER and PR receptors, and the patient has undergone neoadjuvant chemotherapy before excision, then retest ER/PR on the excision.))[note 2]

In breast cancer metastases, retest estrogen and progesterone receptors, and HER2 in the following circumstances:[8]

  • 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. 
  2. Retesting ER/PR on any excision with previously negative ER/PR on biopsy on a patient having received neoadjuvant therapy has no scientific support nor opposition.
    - William M Sikov, MD, FACP, FNCBCJudy C Boughey, MD, FACSZahraa Al-Hilli, MD, FACS, FRCSI. General principles of neoadjuvant management of breast cancer. UpToDate.

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. 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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