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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.

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.

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.

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.

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

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.

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.

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.

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.

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 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.

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. Blokhin National Medical Research Center of Oncology in 2015 to 2018. Treatment included neoadjuvant chemotherapy (NACT) with HER2-blockade and radical surgery followed by the evaluation of a pathologic response in the primary tumor and regional lymph nodes. The patients` age varied from 29 to 71; its median was 51.5; 45.2% of patients had primary operable stages (T 1 -3N 0-1 ) and 54.8% had locally advanced tumors. All the patients had grade 2-3 anaplasia; luminal HER2-positive BC was diagnosed in 41.4% of patients; hormone-negative tumors were seen in 58.9%; 91.5% of patients had Ki-67 ≥20% in 75.3% of patients, preoperative systemic therapy included anthracycline-containing regimens (4AC + 4 x paclitaxel 175 mg/m 2 /12 × weekly administrations of paclitaxel 80 mg/m 2 ; trastuzumab therapy was simultaneously performed with the administration of taxanes in the standard regimen) and anthracycline-free regimen TCH ± Pertuzumab regimen in 24.7% of cases. After NACT patients underwent surgery (radical mastectomy in 78.1%, breast-sparing treatment in 21.9%) with the assessment of morphological findings. Biopsy specimens obtained before the treatment was restudied; HER2 amplification was detected using a Dako HER2 IQFISH pharmDx kit according to its instruction and the 2018 ASCO/CAP guidelines. In 87.1% of cases, the HER2-positive status corresponded to the first category of the 2018 ASCO/CAP criteria for HER2-positive BC; clustered HER2 amplification was found in 30.1% of cases. The authors analyzed the frequency of bpCR and tpCR attainment by various clinical and morphological factors, as well as the impact of a HER2 amplification level on pCR rates., Results: A breast pCR (bpCR) was achieved in 57.4% patients; bpCR and lymph node CR (lnCR) were noted in 48.9% patients. The rates of bpCR significantly depended on female age, chemotherapy regimen, addition of Pertuzumab, and HER2 copy number. That of bpCR in women less than 35 years of age, in those aged 36-50 years, and in those aged older than 50 years was 22.2, 57.7 and 71.9%, respectively (p=0.026). The maximum bpCR rate observed with the TCH±P regimen was 80.0%, that with anthracycline-containing regimes was 52.8% (p=0.045), and the addition of Pertuzumab increased complete response rates up to 88.9% (that with Trastuzumab was 54.2% (p=0.049). The relationship of bpCR rates to the detection of cluster amplification turned out to be highly significant (81% in its detection and 48.9% in its absence (p=0.013). In addition, clustered HER2 amplification was the only significant predictive factor for complete regression in the primary tumor and lymph nodes: in its presence, the tpCR rate reached 68.8% versus 38.7%., Conclusion: Clustered amplification of the HER2 gene is the most significant factor of sensitivity to anti-HER2 therapy for Stage II-III BC, and is associated with the maximum rate of both bpCR and total pCR. Further study of this factor may assist in optimizing the treatment algorithm for HER2 + BC.

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.

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.

Objective: To investigate the expression of PD-L1 in triple-negative and luminal B, HER2-negative breast carcinoma and to assess the association of the tumor PD-L1 status with the prognosis of the disease., Subject and Methods: The PD-L1-status of primary tumor was studied in 72 patients with breast cancer, by using an immunohistochemical method., Results: Differences were found in the incidence of carcinomas with PD-L1 expression in tumor cells depending on the molecular genetic type: there was a positive PD-L1 status in luminal B, HER2-negative tumors in 4 (14.81%) of 27 cases and in triple-negative tumors in 17 (37.78%) of 45 cases. An analysis of tumors after neoadjuvant therapy revealed a positive PD-L1-status in tumor cells in 1 of 18 patients with a moderate residual tumor load and in 6 of 13 with a high residual tumor load (5.56 and 46.15%, respectively), as estimated by the RCB system., Conclusion: The positive PD-L1 status in triple-negative breast cancer was determined more than 2 times as frequently as in luminal B, HER2-negative breast cancer (37.78 and 14.81%). There was a considerable correlation between the high residual tumor load and the positive tumor PD-L1 status.

Breast cancer (BC) is a heterogeneous tumor, the biological characteristics of which vary with its growth and progression. Information on key tumor receptors (ER, PR, HER2, and Ki-67) is the basis for individualizing the diagnostic and treatment algorithm at all BC stages; however, the feasibility of biopsy of distant metastases and the re-testing of the biological subtype of BC in its suspected progression are being actively discussed in clinical practice. This review presents an update on the features of metastasis in different biological BC subtypes and assesses the clinical and prognostic role of biopsy of distant metastases in the lung, bones, liver, and brain. It shows the frequency of discordance in receptor status between primary and recurrent tumors at different sites of metastases, as well as the impact of changes in receptor status on survival rates in different biological BC subtypes. The relevance of performing biopsies in BC progression is shown to be beyond question, because it makes it possible to confirm the fact that the disease progresses, to re-test the biological subtype of recurrent BC, and to find new targets that allow the most effective drug treatment regimens to be used.

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.

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.

Unlabelled: Non-small cell lung cancer (NSCLC) is a main group of lung malignancies. Epigenetic changes are as important as genome structural changes in carcinogenesis. MicroRNA (miRNA) is a class of non-coding single-stranded RNAs that play an important role in the regulation of matrix RNA (mRNA) translation and degradation. MicroRNA expression changes occur in many cancers. According to the field cancerization theory, tumor-adjacent histologically normal tissue takes part in tumor progression by triggering cell transformation. The important clinical implication is that the fields may serve as the basis for a recurrence after surgery. Thus, the aim of our study was to determine the expression levels of miRNAs let-7a, miR-155, and miR-205 in tumor and tumor-adjacent apparently normal tissues to evaluate these changes as potential prognostic markers in NSCLC patients., Methods: The expression of miRNAs let-7a, miR-155, and miR-205 in tumor and tumor-adjacent apparently normal tissues at 2 and 5 cm was determined by real-time PCR with subsequent quantification using a 2-ΔΔСt method. The findings were then analyzed to reveal possible associations with clinical and morphological parameters, such as age, cancer stage, and tumor grade., Results: The expression of miRNA let-7a was found to be significantly lower in tumor than that in tumor-adjacent apparently normal tissue at 2 and 5 cm. In groups of patients older than 63 years with Stage III-IV NSCLC, the expressions of microRNA let-7a and miR-155 in tumor tissue were substantially lower than that in the adjacent normal tissue. Beyond that point, patients with high-grade tumors had also a significantly lower expression of miRNA let-7a in relatively adjacent apparently normal tissue., Conclusion: The findings suggest that miRNA let-7a and miR-155 may be used as poor prognostic markers for patients with NSCLC.

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.

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 34βE12 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.

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-34βE12 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 34βE12 is an informative marker for the differential diagnosis of hPIN with intraductal carcinoma.

The paper presents historical information and literature data on lymphoepitheliomas and lymphoepithelioma-like tumors at various sites. It considers the specific features of their histological structure, a differential diagnostic series, and immunohistochemical markers and gives brief information on treatment and prognosis. The paper depicts a clinical case of lymphoepithelioma-like bladder carcinoma in an 80-year-old woman.

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.

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.

The paper reviews the literature on primary paratesticular tumors. It describes the classification, brief characteristics of liposarcomas and the morphological pattern of the tumor with an immunohistochemical profile. A clinical case of differentiated liposarcoma of the spermatic cord with myxoid and rhabdomyoblastic differentiation is depicted in a 61-year-old man.

According to current views, high-grade prostatic intraepithelial neoplasia is the most likely precursor of prostate adenocarcinoma. This review gives the latest data of genetic, proteomic, and morphological analyses of this neoplasia and touches upon the probems that might arise when searching for new markers for differential diagnosis and prognosis estimation.

Objective: To determine the HER2 status of gastric adenocarcinomas, by using biopsy and intraoperative specimens., Subjects and Methods: Immunohistochemistry and in situ hybridization were used to examine the HER2 status of 346 gastric cancer biopsy and intraoperative specimens., Results: The study conducted on a large Russian sample of 346 patients showed a positive HER2 status in 10.7% of the examined specimens. Intestinal-type adenocarcinomas exhibited a positive HER2 status in 21.4% of the cases. Comparative analysis of the HER2 status in the biopsy and intraoperative specimens indicated that there were differences in the determination of the tumor HER2 status in less than 1% of the examined specimens. The remaining found differences (14.7%) failed to change the tumor HER2 status and to affect the choice of a treatment regimen., Conclusion: The performed investigation has demonstrated that the tumor HER2 status determined in the biopsy specimen significantly reflects the molecular biological properties of gastric cancer and may be clinically used to determine indications for the use of targeted drugs.

Objective: To study tubal morphological changes in different diseases of the female reproductive system and to assess its role in the histogenesis of ovarian cancer., Material and Methods: Surgical materials from 77 patients were examined. In all cases, the uterine tubes were studied totally. According to morphological and clinical diagnoses, the materials obtained from the patients were divided into a few groups including, among other conditions, high-grade ovarian cancer, benign ovarian neoplasms, malignancies of other female reproductive organs, etc. Serous tubal intraepithelial carcinoma (STIC), tubal epithelial dysplasia, and other changes were assessed in each case., Results: In high-grade serous carcinoma (HGSC), there were precancer changes as dysplasia and STIC in the macroscopically intact uterine tubes in 30% of cases. The uterine tubes and ovaries were synchronously involved in 50% of cases. Such changes were absent in the fallopian tubes when the ovaries exhibited low-grade serous carcinoma, a borderline tumor or high-grade carcinoma of another histological form different from HGSC. In other malignancies of the female reproductive system, dysplasia and STIC were identified in 5 (10.9%) of 46 cases in the total examination of the uterine tubes., Conclusion: The findings support the tubal origin hypothesis for HGSC. The investigation clearly demonstrated the need for a total examination of the fallopian tubes not only in tumor lesions of the ovaries and other sites (corpus and cervix uteri, breast), but also during tumor-unassociated surgery.

The paper deals with the unification of requirements for coding the causes of death in circulatory system diseases, by taking into account the recently updated ICD-10 and the Consensus of the Expert Council Task Force on Pathological Anatomy, Ministry of Health of the Russian Federation (27 February 2014).

This report presents the initial results of the first Russian molecular epidemiological study of melanoma. The investigation included 1035 patients with stage IIIB-IV melanoma residing in various regions of Russia. Sequencing of BRAF gene revealed mutation in 627 (60.6%) tumors; c.1799T > A (p.V600E) substitution was detected in 563 cases, and other mutations in 64 melanomas. Frequency of BRAF alterations was significantly higher in patients of younger age (< 50 years: 72.9%; > or = 50 years: 57.1%; p = 0.00003). 710 melanomas included in the study were located in sun non-exposed regions of the skin; this category of tumors was characterized by the highest occurrence of BRAF mutations (63.9%). In conclusion, more than a half of Russian patients with advanced melanoma are potential candidates for the treatment of kinase inhibitors of mutated BRAF.

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.

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.

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.

The classification of tumors of the breast was revised and considerably modified in 2012. The main modifications were applied to epithelial tumors. The clinical types of breast cancer were identified. These were inflammatory and bilateral carcinomas. No substantial amendments were made in the classification of mesenchymal tumors. This paper discusses the new WHO classification of tumors of the breast, 2012, by describing the histological forms and immunohistochemical profile of neoplasms in detail. Its dissimilarities from the previous edition are given. The systems for evaluating medical pathomorphism are detailed.

Non-small cell lung cancer (NSCLC) comprises 80% of all lung cancers and is characterized by multiple genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI). The aim of the study was to analyze of molecular-genetic alterations in tumor and tissue surrounding the tumor to determine genetic features of different histological types of NSCLC and its possible associations with clinicopathological parameters of patients. A microsatellite analysis of chromosomal regions 12p23.3, 2q35, 3p14.2, 3p22.2, 3p26.3, 9p22.1, 17p13.3 was performed. The frequency of genetic alterations in NSCLC was 50% in average. LOH/MSI in the tumor surrounding tissue at 2 and 5 cm. from tumor was not detected. There were statistically significant associations between LOH and/or MSI and the tumor stage, its histological type and smoking status. The found genetic alterations can be used as molecular markers of squamous cell lung cancer in difficult diagnostic cases and appraised as prognostic markers.

Benign metastasizing leiomyoma (ICD.0 8898/1) is a rare phenomenon characterized by multiple benign smooth muscle tumors (metastases) in the organs and tissues of patients with uterine leiomyoma without evidence for another tumor process. This tumor should be differentiated from leiomyosarcoma, at the same time account must be taken of the fact that its morphological criteria are not always effective. Molecular genetic testing is a more accurate method that allows valid differentiation of leiomyoma from leiomyosarcoma. Genetic testing is used to estimate losses of heterozygosity and microsatellite instability, which are characteristic of leiomyosarcoma only. The paper describes a clinical case of benign metastasizing leiomyoma in a 54-year-old patient with uterine myoma and pelvic lymph node metastasis. Molecular genetic testing was carried out using the samples obtained from primary uterine leiomyoma, morphologically altered ovarian tissue, and lymph node metastasis to determine the common origin of tumors in the uterus and lymph node and to reveal the benign or malignant nature of these neoplasms. Despite the fact that the term "benign metastasizing leiomyoma" is widely accepted in the world literature, neither these tumors nor metastases have morphological or genetic signs of malignancy so we consider the term "systemic leiomyomatosis" to better reflect the essence of this process.

The objective of the investigation whose results are given in the paper was to compare a few HER2 testing techniques (immunohistochemistry, fluorescence in situ hybridization, and silver in situ hybridization) for adenocarcinomas of the stomach and esophagogastric junction. Different antibody clones and in situ hybridization kits were comparatively analyzed. Recommendations for the use of different testing methods and for the interpretation of their results are given.