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pathological typing combined with molecular markers, breast cancer pathological diagnosis new era
According to the latest global cancer burden data in 2020, the number of new cases of breast cancer in the world has reached 2.26 million, replacing lung cancer and becoming the most common malignant tumor in the world, and the number of deaths ranks first among women in the world. This reflects that the overall treatment status of breast cancer is still not optimistic. At the same time, breast cancer is a malignant tumor with high molecular heterogeneity, and pathological typing and molecular markers are a conventional diagnosis method.
Therefore, at the 25th National Clinical Oncology Conference and 2022 CSCO Academic Annual Meeting, Professor Liu Yueping from , the Fourth Hospital of Hebei Medical University, focused on teaching the key points of pathological diagnosis in the precise diagnosis and treatment of breast cancer. In order to facilitate the learning of clinical and pathologists, this article will summarize and overview the main contents. Application of the clinical markers of
as we are familiar with, ER, PR, HER-2 and Ki-67 are now used in clinical typing and belong to the most widely used group of immune markers. Only a brief introduction is given to their interpretation. In addition, other indicators will be described one by one.
ER/PR
In 2010, ASCO/CAP issued the ER/PR immunohistochemistry test guide and updated it in 2020, clearly pointing out that the proportion of ER immunoresponse staining in tumor cells in breast cancer specimens is ≥10%, defined as positive; between 1%-9%, defined as weakly positive ; <1%>
HER-2
HER-2 detection currently refers to the "Guidelines for HER-2 Detection for Breast Cancer (2019 Edition)" and the "Expert Consensus on Clinical Diagnosis and Treatment of Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer (2021 Edition)". The specific content has been reported before. It should be noted that the "Chinese Society of Clinical Oncology (CSCO) Breast Cancer Diagnosis and Treatment Guidelines 2022" defines HER2 IHC (+) or (++) and FISH negative as low expression of HER-2, and is used to guide the application of a new generation of anti-HER-2 ADC drugs.
HER-2 low expression interpretation points
Ki-67
When considering Ki-67 IHC to guide breast cancer treatment, the consensus opinions and suggestions given by the IKWG working group are:
1.Ki-67 is a persistent biomarker , how to choose its threshold is crucial;
2.Ki-67 IHC in ER-positive, HER-2-negative T1-T2, N0-N1 stage patients, when Ki-67 ≤5% or Ki-67≥30%, it can assist in determining whether to assist chemotherapy and predict prognosis;
3.Ki-67 IHC in ER-positive, HER-2-negative T1-T2, N0-N1 stages, when Ki-67 ≤5% or Ki-67 ≥30% can assist in determining whether to assist chemotherapy and predict prognosis;
3.Ki-67 When the IHC is in the 5%-30% range, there is a large variation between observers/laboratorys. It is recommended to test for more genes. At the same time, there must be a strict quality assessment and control system to ensure the effectiveness of the analysis.
Breast Cancer Tumor Infiltrating Lymphocytes (TILs) Evaluation
TILs Evaluation is significantly related to better prognosis of TNBC and HER2+ breast cancer, with grade IB evidence; in St Gallen in 2019 and WHO breast tumors, triple-negative breast cancer should be routinely diagnosed; in the 2021 European Society of Oncology Annual Meeting (ESMO), it was pointed out that 30% was recommended as a threshold for phase 1 TNBC adjuvant chemotherapy decisions, and in PD-L1-positive advanced TNBC and HER-2+ breast cancer, it was recommended to express the 5% or 10% TILs threshold to define "immunely enriched" tumors.
Breast cancer tumor infiltration lymphocytes evaluation
PD-L1
Since clinical research adopts the accompanying diagnostic development model of "one drug, one assay", different clinical drugs target different PD-L1 IHC detection platforms, including SP263 (tumor cells), SP142 (tumor cells, immune cells ), 22C3 (tumor cells), 28-8 (tumor cells), etc. Therefore, different PD-L1 scoring systems will inevitably cause heterogeneity.
PD-L1 as the main marker - how should pathological reports be conducted?
Note:
1. Confirm that tumor cells are clearly stained with PD-L1
When magnification is 20 times, tumor cells with clear membrane staining must have: partial or complete staining; staining of any intensity.
2. Confirm PD-L1 staining is tumor-related mononuclear inflammatory cells. Due to the high nucleoplasm ratio in immune cells, cell membrane and cytoplasm staining are usually difficult to distinguish. Cell membrane and/or cytoplasm staining of MICs were counted.
3. Tumor-associated mononuclear inflammatory cell range
adjacent MICs are defined as being in the same 20× field of view as the tumor. MICs that are not directly related to tumor response should be excluded, and macrophages and histocytes are considered to be homogeneous cells.
20×Rules: To identify those monocytes considered adjacent to the tumor, the edges of the tumor mass or tumor nests are placed in the center of the 20× field of view.
Changes in the corresponding marker in the metastasis
Bone metastasis decalcification
For harder specimens, pathologists often need to perform decalcification treatment, but the application of decalcification fluid will damage the tissue's antigen . Therefore, it is necessary to choose the appropriate decalcification solution and decalcification time based on the actual situation.
Acid decalcification solution: often nitric acid and hydrochloric acid, destroy nucleic acid, has an impact on molecular detection and has a certain impact on immunohistochemical detection.
EDTA decalcification solution: has little impact on FISH and DNA/RNA detection.
EDTA-formalin combines decalcification and fixation. It is recommended that bone transfer specimens should be fully fixed before decalcification, and should be fixed in formalin for at least 1 h. Then EDTA decalcification/fixation time is related to tissue size, thickness, and texture, but it needs to be between 6-72 h. Changes in metastatic markers of
(avoid using bone metastasis )
With the advancement and development of medical science and technology, especially the rapid development of NGS technology, leading a major change in precise treatment of breast cancer, more and more tumor mutation driver genes are gradually being explored. At present, the molecular tumor expert group (MTB) model is gradually becoming popular in clinical practice, which can propose a more accurate patient-centered personalized clinical diagnosis and treatment model.
However, there is still a long way to go in the precise diagnosis and treatment of breast cancer. In the future, scientists, medical workers and pharmaceutical companies will need to work closely together to contribute to the precise treatment and marker research of breast cancer.
This article is first published: Medical community pathology channel
Author: No. 4
Editor: Sweet
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