[Analysis of the work of the Immunohistochemical Quality Control Center of the Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia in 2023].

The article demonstrates a detailed analysis of the results of the rounds of quality control of immunohistochemical studies conducted by the Central Committee of the Immunohistochemical Quality Control Center of the Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia in 2023. Typical shortcomings and errors in the immunohistochemical examination of various tumors have been identified and ways to eliminate them are given. Particular attention is paid to defining a panel of standard breast cancer markers and eliminating the shortcomings of immunohistochemical examination of markers of accompanying diagnosis.

[Comparative immunohistochemistry study of different antibodies clones for detection of breast cancer markers (estrogen receptor, progesterone receptor, HER2/neu, Ki-67)].

Objective: A comparative study of detection of breast cancer markers (estrogen receptors, progesterone receptors, HER2/neu, Ki-67) by immunohistochemical method with antibodies produced by PrimeBioMed (Russia) and antibodies produced by Roche Ventana (USA).

Material And Methods: Surgical specimens and biopsies from 37 patients with invasive breast cancer were used. Sections were stained with antibodies of clones ER SP1 and GM030, PR 1E2 and PBM-5B8, HER2/neu 4B5 and PBM-46A6, Ki-67 30-9 and GM010.

Prognostic and predictive role of immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide. The traditional classification of CRC is based on pathomorphological and molecular characteristics of tumor cells (mucinous, ring-cell carcinomas, ), analysis of mechanisms of carcinogenesis involved (chromosomal instability, microsatellite instability, CpG island methylator phenotype) and mutational statuses of commonly altered genes (KRAS, NRAS, BRAF, APC, ), as well as expression signatures (CMS 1-4). It is also suggested that the tumor microenvironment is a key player in tumor progression and metastasis in CRC.

[Assessment of HER2 status of carcinomas of various localizations].

A detailed description of the methodological aspects of the evaluation of HER2-status in carcinomas of such localizations as the mammary gland, pancreas, salivary glands, stomach, colon, endometrium, bladder, lungs is presented. Approaches and criteria for assessing HER2 status from methodological and clinical points of view are analyzed. The data are systematized in tables for use in practical diagnostic work.

[Predictive markers of immunotherapy in cervical cancer].

Objective: Study of PD-L1 expression in squamous and adenosquamous cell cervical cancer (CC) by immunohistochemical (IHC) method, assessment of the relationship between PD-L1 tumor status and its clinical and morphological characteristics, TILs, MSI/dMMR, and HPV tumor status.

Material And Methods: Surgical material was obtained from 41 patients with CC, on which the expression of PD-L1, proteins of the MMR system and p16 was studied by the IHC method, the TILs index was determined.

Results: Positive PD-L1 status was found in 51.

[Updated CAP guidelines for determining molecular biological subtypes of breast cancer].

Updated 2023 guidelines from the College of American Pathologists (CAP) on immunohistochemical detection of human epidermal growth factor receptor type 2 (HER2), receptors of estrogen (ER) and progesterone (PgR), and the cell proliferation marker Ki-67 in breast cancer are presented. Attention is drawn to the emergence of two new terms «ER Low Positive» and «HER2 Low» to characterize tumors with low expression of estrogen receptors and HER2.

[External quality control of immunohistochemical studies in pathomorphology: tasks, problems, solutions, development prospects].

In 2022, the Quality Control Center for Immunohistochemical Studies of the Russian Medical Academy of Continuing Professional Education conducted 12 rounds of markers for breast, lung, prostate, bladder cancer with the participation of 83 laboratories. For the first time, a round was held to control the method of hybridization in the diagnosis of breast cancer, and a digital round. Typical problems in carrying out immunohistochemical studies in oncomorphology have been identified and the importance of participation of laboratories in external control has been shown.

[Investigation of the mutational status of the FGFR3 gene in urothelial bladder carcinoma].

Objective: To study the somatic mutational status of the gene in urothelial bladder cancer (BC) and evaluate its relationship with the clinical and morphological characteristics of the tumor, deficiency of the DNA mismatch repair (dMMR), PD-L1 tumor status, and immunohistochemical (IHC) expression of the p16 protein.

Material And Methods: Surgical material of 40 patients with BC, on which the mutational status of the gene was studied using the molecular genetic method, as well as the MMR status, PD-L1 and p16 expression by the IHC method.

Results: mutations, such as G370C, S249C, S371C/Y373C, R248C, were detected in 35.

[Microsatellite instability and DNA mismatch repair deficiency detection in tumors of various sites].

Microsatellite instability, which is caused by a deficiency in the DNA unpaired nucleotide repair system, is an important pathogenetic event for some tumors. In addition, the detection of this molecular feature becomes an independent prognostic factor in the course of the disease and a predictor for the appointment of therapy with immune checkpoint inhibitors. Immunohistochemistry is a reliable and available method for detecting a deficiency in the DNA mismatch repair system, and it has recommended as a screening for hereditary syndromes associated with microsatellite instability.

The Ring Study: an international comparison of PD-L1 diagnostic assays and their interpretation in non-small cell lung cancer, head and neck squamous cell cancer and urothelial cancer.

PD-L1 immunohistochemistry has been approved as a diagnostic assay for immunotherapy. However, an international comparison across multiple cancers is lacking. This study aimed to assess the performance of PD-L1 diagnostic assays in non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC) and urothelial cancer (UC).

[Results of the work of the Russian Medical Academy of Continuous Professional Education Center for quality control of immunohistochemical studies for 2019-2021].

In 2019-2021 the Russian Medical Academy of Continuous Professional Education Center for quality control of immunohistochemical studies conducted rounds on the most used tumour markers of various localizations. The deficiencies in the conduct of immunohistochemical studies were identified and the importance of the participation of medical organizations in measures to improve the quality control of immunohistochemical studies in oncomorphology was shown.

[Pathomorphological alterations in the kidneys in acute and chronic alcohol intoxication].

The literature review presents data on pathomorphological changes in the kidneys in acute and chronic alcohol intoxication. A lack of consensus among researchers on the direct toxic damage to renal tissue by ethanol is demonstrated. Analysis of the literature showed that the issue of attributing microscopic changes detected in the kidneys to characteristic or specific signs remains controversial.

[Reed nevus and cutaneous melanoma in children: an immunohistochemical study].

Unlabelled: Certain difficulties arise in the differential diagnosis between Reed nevus that is common in children and adolescents and cutaneous melanoma that is extremely rare in patients of this age group. In addition to the classical histological examination, an immunohistochemical test for marker proteins is carried out to improve the accuracy of the diagnosis of pigmented skin neoplasms.

Objective: To evaluate the suitability of a set of proteins (cyclin D1, p16, and HLA class I antigens) in the differential diagnosis of Reed nevus and cutaneous melanoma in children and adolescents.

[The use of intralaboratory and external quality control of immunohistochemical studies to improve the detection of estrogen and progesterone receptors].

Immunohistochemical study of breast cancer has been practiced for several decades; however, the standardization of this process has not yet been achieved, despite substantial advances in methodology. The paper presents practical guidelines and standards for testing breast carcinomas, which can be used as day-to-day control of the work of an immunohistochemistry laboratory. It considers the concept of external quality control in the immunohistochemical detection of estrogen (ER) and progesterone (PR) receptors, as well as the problems of harmonization in the immunohistochemical analysis of breast carcinomas, by using the nuclear biomarkers, such as ER and PR, as an example.

[Immunohistochemical study of MSI markers in breast cancer].

Objective: To investigate the expression of microsatellite instability (MSI) markers, which is detected by an immunohistochemical technique, and to compare the expression with the PD-L1 status in luminal B, HER2-negative and triple-negative breast cancer.

Material And Methods: The investigation included tumors from 40 patients with triple-negative and luminal B, HER2-negative subtypes. Immunohistochemical study was performed using Ventana antibodies: anti-MLH1 (clone M1), anti-MSH2 (clone G219-1129), anti-PMS2 (clone A16-4), and anti-MSH6 (clone SP93).

[The role of the immunohistochemical marker p40 in the differential diagnosis of adenocarcinoma and nonkeratinizing squamous cell cancer of the lung].

Lung cancer is one of the main causes of cancer death. It is a heterogeneous group of malignant neoplasms, the treatment tactics for which directly depends on tumor morphology and genetic characteristics. However, the pathomorphological differential diagnosis of adenocarcinoma and squamous cell cancer of the lung is difficult in some cases and an immunohistochemical (IHC) study is needed to verify these tumors; moreover, the IHC panel should include both squamous cell and pneumocyte markers.

[Epidemiology and diagnosis of mutations in the ALK gene in patients with non-small cell lung cancer in the Moscow region].

Aim Of Study: To determine a diagnostic algorithm for detecting translocation of the gene and its frequency in the Moscow region.

Materials And Methods: During the priod between 2014 and 2018 (inclusive), 488 patients without activating mutations in the gene in the Moscow region were tested. To detect translocation of the ALK gene, fluorescence hybridization (FISH) methods, an immunohistochemical method, and, in some cases, a polymerase chain reaction were used.

[The first experience of PD-L1 testing of triple negative breast cancer with marker SP142 in Russia].

Aim Of Study: To evaluate the pecularities of PD-L1 expression in triple negative breast cancer (TNBC) in the Russian population.

Materials And Methods: For 7 months, within a scientific study of the Russian Society of Clinical Oncology (RUSSCO), we determined the PD-L1 status of 58 patients with TNBC. In each case, an immunohistochemical study was performed in a closed Ventana Bench Mark Ultra automatic stainer using a closed protocol with rabbit monoclonal antibodies Ventana PD-L1 SP142 and Opti View DAB IHC Detection Kit with Opti View Amplification Kit.

Agreement between PDL1 immunohistochemistry assays and polymerase chain reaction in non-small cell lung cancer: CLOVER comparison study.

The goal of the CLOVER study was to perform a pairwise comparison of four tests based on the same patient population with non-small cell lung cancer (NSCLC): three validated PDL1 immunohistochemistry (IHC) assays (Ventana SP142, Ventana SP263, Dako 22C3) and one PCR test. Four hundred seventy-three NSCLC samples were obtained from a biobank and were stained using PDL1 IHC assays. Four trained pathologists independently evaluated the percentage of tumor cells (TC) and immune cells (IC) that stained positive at any intensity.

[Immunohistochemical study of the MSI phenotype of urothelial bladder cancer].

Objective: To investigate the MSI phenotype of urothelial bladder cancer (BC) by immunohistochemistry (IHC) and to assess its relationship to the prognostic factors of the disease and PD-L1 status of BC.

Material And Methods: Using the surgical and biopsy materials obtained from 50 patients with BC during examination and treatment, the investigators studied the MSI phenotype by IHC. A system was proposed to assess the IHC expression of MSI proteins, by taking into account the intensity of nuclear staining and the area occupied by tumor cells with stained nuclei.

[Updated 2018 ASCO/CAP recommendations on the definition of human epidermal growth factor receptor type 2 (HER2) in breast cancer].

A summary of the updated recommendations of the 2018 American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP), devoted to testing type 2 human epidermal growth factor receptor (HER2) in breast cancer.

[Role of clustered HER2/neu amplification as a marker for a special sensitivity to neoadjuvant anti-HER2 therapy with trastuzumab in patients with stage II-III breast cancer].

Objective: To evaluate the influence of clinical and morphological factors and HER2 copy numbers on pathologic complete response (pCR) rates in patients with HER2-positive stage II-III breast cancer (BC).

Material And Methods: Treatment results were studied in 73 patients with HER2-positive Stage II-III BC, who received treatment at the N.N.

[HER2/neu gene amplification as a mechanism of clonal heterogeneity in breast cancer].

Objective: To estimate the heterogeneity of HER2/neu gene amplification in HER2/neu-positive breast cancer (BC).

Material And Methods: Fluorescence in situ hybridization (FISH) assay was used to estimate HER2/neu gene amplification and HER2/CEP17 ratios in BC samples with an immunohistochemical evaluation of HER2/neu2+ expression. The results were interpreted according to the 2018 ASCO/CAP guidelines.

[The expression of EMMPRIN and the matrix metalloproteinase MMP-1 in the cervix uteri and corpus uteri in cervical squamous cell carcinoma].

Objective: To investigate the features of expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the matrix metalloproteinase MMP-1 in the cervix uteri and corpus uteri in cervical squamous cell carcinoma (CSCC).

Material And Methods: The investigation was conducted using the surgical material obtained after hysterectomy in patients diagnosed as having CSCC. RT-PCR, immunohistochemistry (IHC), and enzymatic assays were used.

[Study of the PD-L1 status in breast cancer, by using the SP142 monoclonal antibody, and the prospects for determining treatment policy].

Objective: To investigate the expression of programmed death ligand 1 (PD-L1) in triple-negative and luminal B, HER2-negative breast cancer, by using the SP142 antibody and to assess the association of the PD-L1 status with prognosis for patients.

Material And Methods: The study was conducted using surgical materials (full sections) obtained from 72 patients. The sections were stained with the SP142 PD-L1 antibody.