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.

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.

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 in situ 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.

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.

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 51.2% of the studied CC samples. In the study sample, the level of PD-L1 expression depended on the severity of lymphoid infiltration of the tumor (p=0.038), it was shown that a positive PD-L1 status of CC can be expected with a TILs value greater than or equal to 50%. The age of the patients, the histological variant of the tumor, the pT and pN stage, the presence of lymphovascular invasion, and the HPV status did not statistically significantly affect the level of PD-L1 expression, however, there was an association between the PD-L1 status and the grade of CC malignancy (p=0.027). The presence of the MSI/dMMR phenomenon was detected in a small percentage of carcinomas (4.9%), the PD-L1 status of these tumors was determined as positive.CONCLUSION:A positive PD-L1 status is determined in a significant number of cases of CC, regardless of most of the studied clinical and morphological characteristics; there is a statistically significant relationship between PD-L1 expression and the degree of tumor differentiation and TILs. It has been shown that CC with the MSI/dMMR phenomenon is characterized by a positive PD-L1 status. The authors consider it necessary to study the expression of PD-L1 in patients with cervical carcinomas in order to determine the possibility of prescribing personalized therapy with immune checkpoint inhibitors.

OBJECTIVE:To study the somatic mutational status of the FGFR3 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 FGFR3 gene was studied using the molecular genetic method, as well as the MMR status, PD-L1 and p16 expression by the IHC method.RESULTS:FGFR3 mutations, such as G370C, S249C, S371C/Y373C, R248C, were detected in 35.0% of the studied BC samples. FGFR3 status did not depend on the gender and age of patients, as well as on the degree of tumor lymphoid infiltration (TILs). Statistically significant differences were found in the analysis of FGFR3 status depending on the histological structure and degree of tumor differentiation, as well as on the pT stage. The FGFR3 status of BC was not associated with the IHC expression of the studied proteins of the MMR system, as well as with the PD-L1 status. Higher levels of PD-L1 expression were demonstrated by BC tumor cells, in which no aberrations in FGFR3 were detected. There was no significant association between p16 status and the presence of FGFR3 mutations, but for FGFR3-positive carcinomas, the basal pattern of p16 staining by IHC was noted.CONCLUSION:A positive somatic mutational status of the FGFR3 gene was statistically significantly more common in the group of papillary low-grade non-muscle-invasive BC, demonstrating basal p16 IHC staining. In the study sample, there was no statistically significant relationship between the FGFR3 status of BC and gender and age differences, TILs, MMR status, PD-L1 status (SP142 and 22C3), and p16 status. The results of the study indicate the need to determine the FGFR3 status in patients with BC for further prescription of personalized therapy.

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.

Among the prominent medical scientists of our country, George Vladimirovich Shor, an outstanding Russian pathologist, Doctor of Medicine (1903), Professor (1913), Honored Scientist of the RSFSR (1933), deserves a worthy place.

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). MSI was assessed according to the standard criteria.RESULTS:The PD-L1-positive status was present in 14 (35%) of the 40 patients. Moreover, MSI-H was detected in only 1 (2.50%) case. The two-year survival rate was 87.5%; it should be noted that the median survival rate was not reached either in the study sample or in the groups divided according to PD-L1 and MSI statuses. The overall survival rate for patients with MSI was 75% (3/4).CONCLUSION:The first comparative study of the expression of PD-L1 and immunohistochemical MSI markers, which has been conducted on a small sample, fails to draw unambiguous conclusions, but shows the need to investigate this phenomenon on large samples and by using genetic methods.

The paper presents the life and career of Aleksander Aleksandrovich Bogomolets, outstanding pathophysiologist of the country; famous statesman and public figure; founder of a large scientific school; Academician and Vice-President of the USSR Academy of Sciences; Academician of the UkrSSR Academy of Sciences; Academician of the BelSSR Academy of Sciences; Academician of the USSR Academy of Medical Sciences; Honored Scientist of the RSFSR and UkrSSR; USSR State Prize Winner, and Hero of Socialist Labor.

The paper presents the life and creative career of Professor Alexander Alexandrovich Vasiliev, MD, a prominent Russian pathologist, one of the organizers of Red Army postmortem service, team physician.

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. Fifty surgical and biopsy specimens underwent morphological and IHC studies using antibodies against p40, p63, CK5/6, CK7, and TTF1. In this investigation, p40 showed a higher specificity than another squamous cell differentiation marker, such as p63; this confirms the data that it is advisable to use the marker p40 to verify squamous cell lung carcinoma. If there is a small amount of material for an IHC study in the differential diagnosis of adenocarcinoma from squamous cell cancer of the lung, the optimal solution is to limit the IHC panel to two markers, such as p40 and TTF1.

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.RESULTS:An analysis of the results of an IHG study of MSI protein expression revealed a high direct correlation between the nuclear staining intensity of tumor cells and the percentage of tumor area occupied by the latter. The lack/decrease of the expression of the studied proteins was associated with the stage (T) and the presence of a high-grade tumor. The heterogeneous expression of the studied proteins (PMS2, MLH1, and MSH6) was noted to be 10, 30, and 40%, respectively.CONCLUSION:A high direct correlation was observed between the nuclear staining intensity of tumor cells and the percentage of the area occupied by the latter. There was a relationship between the lack and/or decrease of the expression of MSI proteins (mainly PMS2 and MLH1 and to a lesser extent MSH6) and the grade of BC, as well as stage T; there was a tendency to decrease the expression of the studied proteins in the area of invasive tumor growth, which confirms the prognostic role of MSI proteins. The most pronounced heterogeneity of IHC expression was noted with MSH6; the least one was seen with PMS2. There was a predominance of high-grade surface carcinomas (T1) among the heterogeneously stained tumors. In the case of positive PD-L1 status, there was decreased PMS2 and MLH1 expression and pronounced MSH6 expression; no significant relationship was found due to the small number of these cases. The authors consider it necessary to conduct further studies of the relationship between the MSI phenotype and the PD-L1 status of BC.

Introduction.The goal of the CLOVER study performed by the Russian Society of Clinical Oncology, was a pairwise comparison of three validated PD-L1 immunohistochemical (IHC) tests (Ventana SP142, Ventana SP263, Dako 22C3) in the patient population with non-small cell lung cancer (NSCLC). This study is the first large Russian comparative study to evaluate PD-L1 expression levels using immunohistochemistry methods.Materials and methods.The study was conducted on 473 NSCLC samples from Biobank. The IHC tests were carried out with 3 antibody clones. Four trained pathologists independently evaluated the percentage of positively stained tumor cells (TC) and immune cells (IC). To assess the correlation of TC and IC between different runs and the prognostic values of one test for another, a concordant analysis was used.Results.The number of PD-L1‑positive cells (≥1 %) was higher among IC compared with TC in all three IHC tests. Pearson correlation coefficients (PCC) for TCs were 0.71, 0.87, and 0.75 for 22C3 / SP142, 22C3 / SP263 and SP263 / SP142, respectively. PCC values for ICs were 0.45, 0.61, and 0.68 for the same pairs. A high coincidence of positive and negative results (>91 %) was obtained between the staining with antibodies 22C3 and SP263 of immunooncological agents in the 1st line.Conclusions.The highest correlation between IHC tests was obtained by pairwise comparison of 22C3 and SP263. Clone 22C3 can be considered as a substitute for SP263 in the first-line treatment of NSCLC. Clone SP142 showed weaker expression in TC and IC compared to the other two tests in patients with non-small cell lung cancer.

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. RESULTS Positive PD-L1 status in TNBC was detected in 37.93% of cases. Almost all tumors had an expression level of up to 10%. Only 5.17% of cases showed ligand expression on tumor cells. CONCLUSIONS According to the results of the first experience of testing PD-L1 in TNLM in Russia, it was possible to obtain data comparable to the same data of large international studies. RUSSCO's information and logistic support allows making this analysis available to all citizens of the country.

AIM OF STUDY:To determine a diagnostic algorithm for detecting translocation of the ALK 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 EGFR gene in the Moscow region were tested. To detect translocation of the ALK gene, fluorescence in situ hybridization (FISH) methods, an immunohistochemical method, and, in some cases, a polymerase chain reaction were used.RESULTS:Revealed ALK gene rearrangement in a population of patients with lung adenocarcinoma amounted to an average of 7.6% of cases. With this, the main method that we used was immunohistochemical method, applicable in more than 80% of cases. The use of other methods for verification of abnormalities in the ALK gene was found necessary in rare cases (3.3%).CONCLUSIONS:Using the algorithm presented in the article, it was possible to detect ALK gene rearrangement in a population of patients with lung adenocarcinoma in the Moscow region in an average of 7.6% of cases.

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.RESULTS:Differences were found in the detection rates of the PD-L1-positive status in the primary tumor and regional metastasis (primary tumor in 26 (36.1%) cases and metastasis in 18 (47.4%) of the 38 cases). By and large, the PD-L1-positive status was less common in the patients receiving neoadjuvant chemotherapy (25.8% versus 53.7%); however, it should be noted that the PD-L1-positive status was more often detected in those who had a higher residual cancer burden (RCB) (RCB-III versus RCB-II).CONCLUSION:Considering the findings, it is necessary to clarify the status of not only a primary focus, but also clinically significant metastases, especially if the primary tumor has yielded a negative result. The patients with disease progression who receive standard therapy regimens may have a chance for a good result when using PD-1/PD-L1 blockers. At the same time, the association of the PD-L1 status with RCB may affect the choice of adjuvant treatment policy.

Background. Urothelial cancer ranks 7th and 17th of all the malignant tumors in males and females, respectively. Development of new immunotherapeutic drugs provides new possibilities in treatment of such patients, especially the patient population in whom platinum‑based therapy is contraindicated. Administration of immunooncology drugs requires determination of PD-L1, for which various diagnostic systems are used. The question regarding correlation of results of determination of PD-L1 expression remains of concern.Materials and Methods. The study was performed on 100 samples of surgical and biopsy samples of urothelial cancer. Two clones of 22C3 and SP142 with corresponding detection systems were used for the study. PD-L1 expression was assessed in tumor and immune cells.Results. The study demonstrated a high correlation of negative PD-L1 tumor status determined using both diagnostic agents (92 % and 97 %) and low correlation of results of positive PD-L1 status (67 % and 43 %).Conclusions. Thus, if a negative result of PD-L1 status of urothelial cancer is obtained using any of the diagnostic agents studied, repeated test with the other antibody is not required. If positive status is obtained in one test, the patient may have a negative status in the other test, which allows recommending a repeated testing in borderline cases using a test, recommended for the medicinal product untended for treatment.

Background.  Urothelial cancer ranks 7th and 17th of all the malignant tumors in males and females, respectively. Development of new immunotherapeutic drugs provides new possibilities in treatment of such patients, especially the patient population in whom platinum‑based therapy is contraindicated. Administration of immunooncology drugs requires determination of PD-L1, for which various diagnostic systems are used. The question regarding correlation of results of determination of PD-L1 expression remains of concern. Materials and Methods.  The study was performed on 100 samples of surgical and biopsy samples of urothelial cancer. Two clones of 22C3 and SP142 with corresponding detection systems were used for the study. PD-L1 expression was assessed in tumor and immune cells. Results.  The study demonstrated a high correlation of negative PD-L1 tumor status determined using both diagnostic agents (92 % and 97 %) and low correlation of results of positive PD-L1 status (67 % and 43 %). Conclusions.  Thus, if a negative result of PD-L1 status of urothelial cancer is obtained using any of the diagnostic agents studied, repeated test with the other antibody is not required. If positive status is obtained in one test, the patient may have a negative status in the other test, which allows recommending a repeated testing in borderline cases using a test, recommended for the medicinal product untended for treatment.