[Updated CAP guidelines for determining molecular biological subtypes of breast cancer]. / Obnovlennye rekomendatsii CAP po opredeleniyu molekulyarno-biologicheskikh podtipov raka molochnoi zhelezy.

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 Positive¼ and «HER2 Low¼ to characterize tumors with low expression of estrogen receptors and HER2.

[Assessment of HER2 status of carcinomas of various localizations]. / Opredelenie HER2-statusa kartsinom razlichnykh lokalizatsii.

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]. / Prediktivnye markery immunoterapii v rake sheiki matki.

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.

[Immunohistochemical study of the MSI phenotype of urothelial bladder cancer]. / Issledovanie MSI-fenotipa urotelial'nogo raka mochevogo puzyria immunogistokhimicheskim metodom.

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.

[Study of the PD-L1 status in breast cancer, by using the SP142 monoclonal antibody, and the prospects for determining treatment policy]. / Issledovanie PD-L1-statusa raka molochnoi zhelezy s ispol'zovaniem monoklonal'nogo antitela SP142 i perspektivy dlia opredeleniia lechebnoi taktiki.

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.

[Updated 2018 ASCO/CAP recommendations on the definition of human epidermal growth factor receptor type 2 (HER2) in breast cancer]. / Obnovlennye rekomendatsii 2018 g. ASCO/CAP po opredeleniiu retseptora épidermal'nogo faktora rosta cheloveka 2-go tipa (HER2) pri rake molochnoi zhelezy.

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.

[Smooth muscle tumors of uncertain malignant potential]. / Gladkomyshechnye opukholi s neopredelennym zlokachestvennym potentsialom.

OBJECTIVE: To investigate microsatellite instability in smooth muscle tumors of uncertain malignant potential and to compare the results with clinical and morphological data. SUBJECT AND METHODS: Histological and immunohistochemical studies were conducted in 26 patients aged 30-63 years (mean age, 37 years) with leiomyomatosis; which revealed intravenous leiomyomatosis in 20 cases, metastasizing leiomyoma in 2, disseminated peritoneal leiomyomatosis in 3, and smooth muscle tumor of uncertain malignant potential in 1 case. Microsatellite instability was studied by fragment analysis on a genetic analyzer using a test system of six markers: D10S1146, D10S218, D10S24, D10S1213, D3S1295, and D9S942. RESULTS: Microsatellite repeat changes characteristic of leiomyosarcomas (heterozygosity loss and/or microsatellite instability in at least one locus studied) were found in 6 patients; all were clinically and morphologically diagnosed as having intravenous leiomyomatosis. In 3 of these 6 cases, leiomyomatosis was accompanied by metastases to the lungs and spread to the peritoneum; heart damage was noted in 2 cases. The data analysis did not allow identification of any significant clinical and morphological criteria for this group. CONCLUSION: Leiomyomatosis is not a transitional form from benign leiomyoma to leiomyosarcoma, as evidenced by the difference in the status of molecular markers. Analysis of molecular genetic changes in DNA from tumor tissue samples cannot categorically clarify the nature of the disease by identifying the signs of genetic instability; however, there is a need for further accumulation of experience in studying tumors of this group and in identifying the possible association with disease prognosis.

[Fatty acid synthase in the diagnosis of prostate neoplasms]. / FASN v diagnostike novoobrazovanii predstatel'noi zhelezy.

The differential diagnosis of benign and malignant changes in the prostate presents still definite difficulties; the antibody panel existing for these purposes is imperfect. Fatty acid synthase (FASN) is an androgen-regulated enzyme required for de novo lipogenesis. A number of studies have noted increased expression of the gene encoding this protein in tumors and precancerous lesions of different locations. AIM: Тo estimate the diagnostic value of analyzing the expression of FASN in prostate neoplasias. MATERIAL AND METHODS: Surgical specimens were selected for study from 71 patients with prostate cancer during radical prostatectomy. An immunohistochemical method was used to analyze FASN expression. RESULTS: The expression of FASN was observed to be moderate or intensive in adenocarcinoma and high-grade prostatic intraepithelial neoplasia (hPIN) in all the study samples while 2 cases showed none and weak expression of AMACR. In benign lesions, the expression of this protein was identified only in 3 cases and it was characterized by a low-intensity staining. CONCLUSION: The study has shown that the high frequency of FASN expression in hPIN and cancer and no expression in most structures of benign hyperplasia make it possible to use this protein as an additional marker in the differential diagnosis of prostatic neoplasms.

[Procedure for intraoperative material examination in breast cancer after neoadjuvant therapy to estimate residual cancer burden using the RCB system].

Currently, neoadjuvant therapy has been shown to be effective in treating HER2-positive breast cancer; the development and assessment of novel medications and therapy regimens are being continued. A tumor response to the treatment is the most important factor in planning adjuvant therapy. The use of different systems to evaluate a therapeutic effect gives rise to significant differences in estimating the rate of complete morphological regression according to the results of performed therapy. The paper describes a procedure to estimate cancer burden using the RCB system. This procedure is highly reproducible and recommended by the 2015 European Society for Medical Oncology Clinical Practice Guidelines for the management of primary breast cancer.

[Estimation of the diagnostic potential of APOD, PTOV1, and EPHA4 for prostatic neoplasms]. / Otsenka diagnosticheskogo potentsiala APOD, PTOV1 i EPHA4 dlya novoobrazovanii predstatel'noi zhelezy.

Prostate cancer is one of the most frequently detected malignancies in men. The gold standard for its diagnosis is morphological examination; at the same time the differential diagnosis of adenocarcinoma, high-grade prostatic intraepithelial neoplasia (HGPIN), and benign conditions that are able to mimic the malignancies is tremendously difficult in a number of cases, this being so, the hyperdiagnosis rate of HGPIN requiring mandatory repeat biopsy is as high as 24%. The currently available differential diagnostic panel of antibodies is imperfect, which necessitates a search for novel markers. AIM: to estimate the diagnostic and prognostic value of the expression of PTOV1, APOD, and EPHA4 in prostatic neoplasias. MATERIAL AND METHODS: A total of 90 samples from prostate cancer patients who had undergone radical prostatectomy were examined. The presence of adenocarcinoma and HGPIN was verified by immunohistochemical tests using antibodies to AMACR (P504S) and high molecular weight cytokeratin 34ßE12 in serial sections. The latter were also used to immunohistochemically analyze the expression of PTOV1, APOD, and EPHA4. RESULTS: APOD expression was noted in 76% of cases of both adenocarcinomas and HGPIN, in 4% in only cancer, and in 7% in only HGPIN. All the study samples showed a considerable decrease in PTOV1 expression in cancer and HGPIN compared to morphologically normal glands. Three samples also exhibited no PTOV1 expression in a number of morphologically normal glands. No difference was found in the expression of EPHA4 in morphologically normal glands, HGPIN, or cancer. CONCLUSION: The high rate of APOD expression in HGPIN and cancer, as well as the absence of its expression in the vast majority of morphologically normal glands allows the use of this protein as an additional marker in the differential diagnosis of prostatic neoplasms. The emerging trends in the difference of PTOV1 expression in morphologically normal prostate tissue, HGPIN, and cancer call for further investigations with a larger sample.

[A new WHO classification of prostate tumors]. / Novaya klassifikatsiya VOZ opukholei predstatel'noi zhelezy.

The paper reviews the 2016 WHO classification of prostate tumors, notes the alterations made, and describes approaches to the diagnosis of cancer types and grades. It also gives original photomicrographs from the authors' collection. The main alterations were as follows: - The types of prostate adenocarcinoma were added by pleomorphic giant-cell carcinoma; oncocytic (8290/3) and lymphoepithelial (8082/3) carcinomas were excluded. - Grade III prostatic intraepithelial neoplasia (PIN) was substituted for high grade PIN (8148/2). - Intraductal carcinoma (8500/2) was added. - Basal cell adenoma (8147/0) was excluded. - Carcinoids were referred to as low-grade neuroendocrine tumors according to the current terminology; large cell neuroendocrine cancer (8013/3) was added. - Paraganglioma (8613/3) and neuroblastoma (9500/3) were excluded. Stromal tumors were grouped with mesenchymal neoplasms. -Malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, chondroma, and hemangiopericytoma were excluded. - Synovial sarcoma (9040/3), inflammatory myofibroblastic tumor (8825/1), osteosarcoma (9180/3), undifferentiated pleomorphic sarcoma (8802/3), solitary fibrous tumor (8815/1), and malignant solitary fibrous tumor (8815/3) were added. The section of lymphoproliferative diseases was extended. The tumors of unknown origin included paraganglioma and neuroblastoma from a group of neuroendocrine tumors. The TNM staging was completely consistent with the 2010 AJCC version.

[A new classification of ovarian tumors].

In 2014, the WHO published a new classification of ovarian tumors. Modifications refer to all nosological entities, touching on epithelial tumors to a greater extent. The performed studies and the accumulated experience could reveal new mechanisms for the pathogenesis of epithelial neoplasms, identify a new morphological group of seromucinous tumors, and make changes in the grading system for serous carcinomas. The paper discusses the changes made in the 2014 WHO classification of ovarian tumors, by describing their nosological entities and comparing it with the previous revision.

[Diagnostic value of estimation of ERG expression in prostate adenocarcinoma and high-grade prostatic intraepithelial neoplasia].

OBJECTIVE: to estimate the diagnostic and prognostic value of analyzing the abnormal overexpression of the chimeric protein ERG, encoded by the chimeric gene TMPRSS2/ERG, in prostatic neoplasias. MATERIAL AND METHODS: A total of 100 prostate adenocarcinoma samples were examined. The presence of tumor and high-grade prostatic intraepithelial neoplasia (hPIN) was verified by immunohistochemical tests using anti-P504S and anti-34ßE12 antibodies in serial sections; RT-PCR was employed to analyze the chimeric transcript TMPRSS2/ERG in 30 prostate adenocarcinoma samples. RESULTS: ERG expression was noted in 46% of the adenocarcinomas and in 21% of hPIN. Eight (8%) patients were observed to have heterogeneous ERG expression: the marked reaction in some tumor portions was concurrent with its complete absence in others. Furthermore, there was ERG expression in all cases of intraductal (noninvasive) carcinoma (the foci of intraductal carcinoma were assessed as atypical cribriform lesions by light microscopy). The prognostic value of ERG expression could not be determined at the current stage of the investigation. CONCLUSION: The relatively low rate of ERG-positive hPIN counts in favor of the limited role of this marker in the differential diagnosis of hPIN. ERG in combination with P504S and 34ßE12 is an informative marker for the differential diagnosis of hPIN with intraductal carcinoma.

[Intravascular leiomyomatosis].

Intravenous leiomyomatosis is a rare disease from a group of tumors with the indefinite grading potential. The paper describes two cases of intravenous leiomyomatosis with its detailed morphological pattern, molecular genetic findings, and a brief literature review. Losses of heterozygosity of microsatellite repeats thatwere located on chromosome 10 in 10q22.1 and common in uterine leiomyosarcomas were found in both cases. Investigations of the morphological and biological characteristics of leimyomatosis are important to clarify the key molecular mechanisms underlying the development of this nosological entity and to determine etiopathogenetic relationships between intravenous leiomyomatosis and other uterine smooth muscle neoplasms.

[New approaches to the classification, grading, and prognosis of renal cell carcinoma].

Renal cell carcinoma is a heterogeneous group of tumors. Frequent revisions of its histological classification and TNM staging system complicate the retrospective studies of large patient groups and hamper the estimation of survival rates and quality of life for patients. Due to improving therapeutic possibilities, the problems of the staging, morphological diagnosis, grading, and determination of prognostic factors of renal cell carcinomas have assumed a particular significance. Despite the long-term history of studies dealing with renal cell carcinoma, there is no general agreement among specialists at to these issues. The paper reviews the recent International Society of Urological Pathology Consensus held in Vancouver in March 2013.

[Metanephric adenoma of the kidney].

The paper describes metanephric adenoma, a rare adenoma, diagnosed in a patient 20 years after surgery. It provides a histological description of the tumor and a concise review of the literature.

[Prognostic value of the expression of adhesion molecules for non-clear-cell variants of renal cell carcinoma].

The prognostic value of the expression of the adhesion molecules CD44, EMA, and E-cadherin was studied using surgical specimens of 105 renal cell carcinomas (54 papillary, 39 chromophobic, and 12 clear-cell ones). Stages 3-4 tumors showed hyperexpression of all the above proteins (the distribution was estimated by chi2 and Fisher's exact tests). Furthermore, CD44 was found to be an independent unfavorable factor to predict renal cell carcinoma: with its hyperexpression, the 5-year estimated survival rate decreased by 52% (Kaplan-Meier method; p = 0.018). The expression of EMA and E-cadherin was significantly associated with the stage and, to some extent, grade of tumor differentiation; however, it is necessary to study more observations to define the prognostic role of these proteins.

[Prognostic factors of renal cell carcinoma].

The crucial predictor of renal cell carcinoma (RCC) is a clinical stage, although the significance of this parameter isn 't confirmed for all histological types of carcinomas. It remains unknown what factors ensure the sensitivity of the tumor to chemotherapy and why metastasis is accompanied by the development of resistance to therapy. The data about the prognosis of RCC rare variants are extremely scarce. Ubiquitin-dependent proteolysis plays an important role in the development of RCC, but the prognostic significance of this signal way's proteins is poorly understood. In order to find out significant factors for prognosis of RCC clinical course it's necessary to use the complex spectrum of tumor growth regulation factors and genetic tests.

[Current views of the molecular mechanisms of gastric cancer progression].

The available technologies have expanded our knowledge about the mechanisms of oncoprogression. Studies of the Wnt signaling pathway in the neoplastic cells could identify new promising markers in assessing the course and prognosis of this disease. beta-catenin as a key protein of the Wnt pathway is involved in the regulation of tumor proliferative activity and in the processes of epithelial-mesenchymal transformation, by regulating E-cadherin metabolism and affecting the close contacts of the gastric epithelium. A competitive interaction between P-cadherin and beta-catenin without forming reasonably close contacts is another cause of impaired intercellular interactions and tumor metastases. Claudin-1 expression in the tumor pool as a marker of invasion requires further investigations. Traditional markers of proliferation and apoptosis, such as Ki-67, p53, and bcl-2, may be further used to estimate the rate of tumor growth.