[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.

[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.

[Investigation of the mutational status of the FGFR3 gene in urothelial bladder carcinoma]. / Issledovanie mutatsionnogo statusa gena FGFR3 v urotelial'noi kartsinome mochevogo puzyrya.

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.

[Mucins expression in gastric cancer: connection of MUC status with clinical, morphological and prognostic characteristics of the tumor]. / Ekspressiya mutsinov v rake zheludka: svyaz' MUC-statusa s kliniko-morfologicheskimi i prognosticheskimi kharakteristikami opukholi.

OBJECTIVE: Clarification of the prognostic value and relationship of MUC-phenotypes of gastric cancer with clinical and morphological parameters. MATERIAL AND METHODS: Surgical material from 310 patients with a verified diagnosis of gastric cancer was studied. Samples were immunohistochemically stained with antibodies to MUC2, CD10, MUC5AC. The results were compared with clinical and morphological characteristics of gastric cancer and patient survival data. RESULTS: The MUC-null and MUC-mix groups significantly differ in the prevalence of subtotal/total tumors from the MUC-I group (p=0.022 and p=0.007, respectively), where there are significantly fewer such tumors. Tubular tumors were more common in the MUC-null group compared to the MUC-G (p=0.026) and MUC-mix (p=0.006) groups, and there were fewer cases with the presence of "signet-ring" cells in the MUC-null group (p=0.000). When studying the discohesive histological type, the literature data on smaller tumor sizes and a lower frequency of lymph node metastasis for MUC-G status were not confirmed, but a more frequent proximal localization of MUC-I tumors was found (p=0.003). No statistically significant differences in survival were found in the analysis of the total sample. Differences in survival were found only in discohesive cancers, where the best survival was recorded for the MUC-null group, and the worst for the MUC-mix group (p=0.022). MUC status is not an independent predictor of gastric cancer (HR=1.662, p=0.093). CONCLUSION: Between tumors with different MUC statuses, there were differences in localization and belonging to individual histological types. Significant differences in survival were found only for discohesive cancers with MUC-null and MUC-mix statuses. Separation of gastric cancers according to MUC status may have only limited predictive value in selected histological forms of cancer.

[Microsatellite instability and DNA mismatch repair deficiency detection in tumors of various sites]. / Opredelenie mikrosatellitnoi nestabil'nosti i sostoyaniya genov reparatsii nesparennykh nukleotidov DNK pri opukholyakh razlichnykh lokalizatsii.

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. This article discusses the advantages and disadvantages of this research method from the point of view of the practitioner.

[Microsatellite instability in gastric cancer is a predictor of a favorable prognosis]. / Mikrosatellitnaya nestabil'nost' v rake zheludka ­ prediktor blagopriyatnogo prognoza.

OBJECTIVE: Evaluation of the frequency of microsatellite instability in gastric adenocarcinomas in patients of the Russian Federation, determination of the relationship of microsatellite instability with clinical and morphological characteristics and the impact on the prognosis. MATERIAL AND METHODS: We used samples of surgical material from 310 patients with a verified diagnosis of gastric cancer. The age of the patients ranged from 22 to 85 years (mean 63 years). The median follow-up of patients was 83 months. Each sample was immunohistochemically stained with antibodies to microsatellite instability markers MLH1, MSH2, MSH6, and PMS2. The results were compared with the main clinical and morphological characteristics of gastric cancer and data on patient survival. RESULTS: The frequency of detection of MMR-negative tumors in the Russian population is 8.1% of all patients with gastric cancer. It was found that patients with MMR-negative gastric carcinomas are older (mean age 69 years, p=0.008). In this group predominates distal localization of tumors, type 2 according to R. Bormann classification (p=0.010), tubular histological type (p=0.010), intestinal subtype according to P. Lauren classification (p=0.003). There were no significant differences between MMR-negative and MMR-positive tumors in terms of other clinical and morphological parameters (including the stage of the tumor process). The overall median survival of patients with MMR-negative tumors was 76%, which significantly (p=0.013) exceeds that in the group of MMR-positive tumors (36%). It was found that despite significant differences in survival, MMR-status is not an significant prognostic factor in gastric cancer (HR=0.983). CONCLUSION: The established differences in patient survival make it possible to distinguish a group of MMR-negative tumors into a separate pathogenetic subtype of gastric cancer (MSI subtype) based on immunohistochemical studies. This subtype occurs predominantly in elderly patients with tubular gastric adenocarcinomas and is characterized by a favorable prognosis.

[Influence of platelets growth factors on spermatogenesis after electronic irradiation]. / Vliyanie faktorov rosta trombotsitov na spermatogenez posle oblucheniya elektronami.

BACKGROUND: The number of cases of male infertility is steadily growing every year, and therefore it is necessary to develop new methods for the diagnosis and treatment of this disease. It is known that plasma enriched with platelets, the α-granules of which contain growth factors, possesses high regenerative activity; therefore, we can expect positive results from its use for the restoration of spermatogenic epithelium. OBJECTIVE: Morphological assessment of spermatogenesis after local ß-irradiation with a dose of 8 Gy and the introduction of growth factors. MATERIAL AND METHODS: Wistar rats (n=135) were divided into groups: I - Control, II - 8IR, III - 8IR+LP-PRP+IGF, IV - 8IR+LP-PRP, and V - LP-PRP. Spermatogenesis in animals of groups II, III, and IV was inhibited by a single local irradiation with 8 Gy electrons. Then, for 11 weeks, LP-PRP was injected intraperitoneally to rats III and IV, and in group III - additionally IGF-1. The testes were examined by light microscopy, computer morphometry, micro-CT, and Western blotting. RESULTS: After irradiation, a decrease in spermatogenic epithelium and the number of germ cells was observed up to sub- and total germinal aplasia, fibrosis and an increase in the expression of caspase-3. Against the background of LP-PRP+IGF administration, the decrease in the proportion of germ cells (hypospermatogenesis) was less pronounced. CONCLUSION: The introduction of growth factors and other biologically active substances released from the α-granules of LP-PRP platelets leads to a delayed decrease in the quantitative and qualitative indicators of spermatogenesis, and the additional administration of IGF-1 enhances the regenerative processes that counteract the development of the effects of electron irradiation with a dose of 8 Gy.

[PD-L1 expression in EBV-associated gastric carcinomas]. / Ekspressiya PD-L1 v EBV-assotsiirovannom rake zheludka.

OBJECTIVE: Assessment of the incidence of PD-L1 expression in EBV-associated gastric adenocarcinomas, as well as clarification of the clinical and morphological characteristics and median survival of patients with PD-L1-positive EBV-associated gastric cancer. MATERIAL AND METHODS: Samples of surgical material from 127 patients with stomach cancer were studied. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). Expression of PD-L1 was assessed immunohistochemically (PD-L1 SP263, PD-L1 SP142). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer and median survival of patients. RESULTS: The detection rate of PD-L1 SP263 and PD-L1 SP142 in EBV-associated gastric adenocarcinoma in our sample was 100% and 76.9% respectively, thus, PD-L1 expression (SP263, SP142) is significantly more frequently detected in EBV-associated gastric carcinomas. It was found that patients with positive expression of PD-L1 in EBV-associated gastric carcinomas are younger (mean age 56.3 years for SP263 and 55.6 years for SP142), belonging to male gender. In addition, this group is dominated by proximal localization of tumors, ulcerative form of growth, tubular histological type, intermediate subtype according to P. Lauren. These characteristics do not depend on the antibody clone: positive expression of SP142 and SP 263 was detected in the same patients with a few exceptions. The overall median survival of patients with positive PD-L1 status SP263 in EBV-associated gastric carcinomas was 35 months, for patients with positive PD-L1 status SP142 - 25 months. Median survival of SP142 PD-L1 positive patients is higher than overall median survival of PD-L1 negative patients in EBV-associated gastric carcinomas. It was found that PD-L1 status in EBV-associated gastric cancer is not a significant prognostic factor. CONCLUSION: A single PD-L1 status does not significantly affect the prognosis in patients with gastric cancer, including those in the group of EBV-associated carcinomas, and can only be considered in conjunction with 'classic' clinical and morphological characteristics, primarily with the stage of the tumor process, since they determine the prognostic properties of the tumor.

[Study of gastric adenocarcinomas association with the Epstein-Barr virus-encoded small RNAs]. / Issledovanie assotsiatsii adenokartsinom zheludka s malymi virusnymi RNK virusa Epshteina­Barr.

OBJECTIVE: Assessment of the incidence of EBV-associated gastric adenocarcinomas in a sample of Russian patients, as well as clarification of the clinical and morphological characteristics and median survival of patients with EBV-associated gastric cancer. MATERIAL AND METHODS: We used samples of surgical material from 282 patients with a verified diagnosis of gastric cancer. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer. RESULTS: The detection rate of EBV-associated gastric adenocarcinoma in our sample was 9.57%. EBER-positive tumors much more often (p=0.021) belong to the intermediate type according to the P. Lauren classification (66.67%) in comparison with EBER-negative tumors (38.82%). EBER-positive tumors significantly more often (p=0.035) belong to high-grade tumors - 75.00% in comparison with EBER-negative tumors (52.13%). The overall median survival of all patients with EBER-positive tumors (53.5 months) was higher compared to the overall median survival of all patients with EBER-negative tumors - 36.5 months (p=0.5379). The median survival of patients with EBER-positive stage III tumors (30.0 months) was also higher compared to that for patients with EBER-negative tumors - 20.0 months (p=0.5622). It was found that a single EBER status is not a significant prognostic factor (HR=1.0143; CI: 0.9897-1.0196). CONCLUSION: Separately taken EBER-status is not a significant independent prognostic factor and can be considered only in conjunction with the «classical¼ clinical and morphological characteristics, primarily with the stage of the tumor process, since it is they that determine the prognostic properties of the tumor.

[Immunohistochemical study of MSI markers in breast cancer]. / Immunogistokhimicheskoe issledovanie markerov MSI pri rake molochnoi zhelezy.

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 role of the immunohistochemical marker p40 in the differential diagnosis of adenocarcinoma and nonkeratinizing squamous cell cancer of the lung]. / Rol' immunogistokhimicheskogo markera p40 pri differentsial'noi diagnostike adenokartsinomy i ploskokletochnogo neorogovevayushchego raka legkogo.

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.

[The first experience of PD-L1 testing of triple negative breast cancer with marker SP142 in Russia]. / Pervyi opyt PD-L1-testirovaniya troinogo negativnogo raka molochnoi zhelezy markerom SP142 v Rossii.

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.

[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.

[Epidemiology and diagnosis of mutations in the ALK gene in patients with non-small cell lung cancer in the Moscow region]. / Epidemiologiya i diagnostika mutatsii v gene ALK u patsientov s nemelkokletochnym rakom legkogo v Moskovskoi oblasti.

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.

[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.

[The expression of EMMPRIN and the matrix metalloproteinase MMP-1 in the cervix uteri and corpus uteri in cervical squamous cell carcinoma]. / Ékspressiia EMMPRIN i matriksnoi metalloproteinazy MMP-1 v sheike i tele matki pri tservikal'noi ploskokletochnoi kartsinome.

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. RESULTS: The high expression of EMMPRIN and MMP-1 in CSCC was found not only in cervical carcinoma, but also in the stroma and epithelium of the cervix uteri and corpus uteri outside the tumor, whereas the level of MMP-1 expression in the morphologically intact tissue was significantly lower than in the tumor, while that of EMMPRIN gene expression did not differ substantially. CONCLUSION: The expression of EMMPRIN and MMP-1 in CSCC occurs in both the tumor and the morphologically intact tissue, which may suggest that the invasive potential of tumor may increase and therefore have prognostic value.

[PD-L1 status in breast cancer]. / PD-L1-status raka molochnoi zhelezy.

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.

[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.

[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]. / Rol' klasternoi amplifikatsii gena HER2/neu kak markera 'osoboi' chuvstvitel'nosti k neoad''iuvantnoi anti-HER2-terapii trastuzumabom pri rake molochnoi zhelezy II­III stadii.

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 (T1-3N0-1) 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/m2/12 × weekly administrations of paclitaxel 80 mg/m2; 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.