[Comparative immunohistochemistry study of different antibodies clones for detection of breast cancer markers (estrogen receptor, progesterone receptor, HER2/neu, Ki-67)]. / Sravnitel'noe issledovanie antitel razlichnykh klonov dlya vyyavleniya markerov raka molochnoi zhelezy (retseptorov estrogenov, progesterona, HER2/neu, Ki-67) immunogistokhimicheskim metodom.

OBJECTIVE: A comparative study of detection of breast cancer markers (estrogen receptors, progesterone receptors, HER2/neu, Ki-67) by immunohistochemical method with antibodies produced by PrimeBioMed (Russia) and antibodies produced by Roche Ventana (USA). MATERIAL AND METHODS: Surgical specimens and biopsies from 37 patients with invasive breast cancer were used. Sections were stained with antibodies of clones ER SP1 and GM030, PR 1E2 and PBM-5B8, HER2/neu 4B5 and PBM-46A6, Ki-67 30-9 and GM010. RESULTS: There was a high positive and significant correlation between the immunohistochemistry results and antibodies of the clones ER-SP1 and GM030, PR1E2 and PBM-5B8, HER2/neu4B5 and PBM-46A6, Ki-67 30-9 and GM010. CONCLUSION: The study showed the possibility of using antibodies of clones GM030, HER2/neu 4B5, PBM-46A6, GM010 (PrimeBioMed) on the Ventana Bench Marck Ultra automatic immunostainer using the detection system UltraView Universal DAB Detection Kit.

[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.

[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.

[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.

[External quality control of immunohistochemical studies in pathomorphology: tasks, problems, solutions, development prospects]. / Vneshnii kontrol' kachestva immunogistokhimicheskikh issledovanii v patomorfologii: zadachi, problemy, puti resheniya, perspektivy razvitiya.

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.

[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.

[Results of the work of the Russian Medical Academy of Continuous Professional Education Center for quality control of immunohistochemical studies for 2019-2021]. / Itogi raboty Tsentra kontrolya kachestva immunogistokhimicheskikh issledovanii FGBOU DPO «RMANPO¼ za 2019­2021 gg.

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

[Pathomorphological alterations in the kidneys in acute and chronic alcohol intoxication]. / Patomorfologicheskie izmeneniya v pochkakh pri ostroi i khronicheskoi alkogol'noi intoksikatsii.

The literature review presents data on pathomorphological changes in the kidneys in acute and chronic alcohol intoxication. A lack of consensus among researchers on the direct toxic damage to renal tissue by ethanol is demonstrated. Analysis of the literature showed that the issue of attributing microscopic changes detected in the kidneys to characteristic or specific signs remains controversial. Some authors identify several characteristic microscopic patterns in the kidney tissue in alcohol intoxication: thickening of glomeruli basal membranes, narrowing of glomerular capsule tubular lumen. Fatty dystrophy of the proximal tubules is most often indicative of concomitant conditions related to alcohol intoxication, such as ketoacidosis. In alcohol intoxication, some changes in the kidneys occur variably, such as dyscirculatory, dystrophic, pigmentary, necrotic, and autolytic changes. Data on the causes of their occurrence are often contradictory from different authors. The authors of this review believe that this issue can be resolved using up-to-date histochemical, immunohistochemical, and morphometric test methods.

[Reed nevus and cutaneous melanoma in children: an immunohistochemical study]. / Nevus Rida i melanoma kozhi u detei. Immunogistokhimicheskoe issledovanie.

Certain difficulties arise in the differential diagnosis between Reed nevus that is common in children and adolescents and cutaneous melanoma that is extremely rare in patients of this age group. In addition to the classical histological examination, an immunohistochemical test for marker proteins is carried out to improve the accuracy of the diagnosis of pigmented skin neoplasms. OBJECTIVE: To evaluate the suitability of a set of proteins (cyclin D1, p16INK4a, and HLA class I antigens) in the differential diagnosis of Reed nevus and cutaneous melanoma in children and adolescents. MATERIAL AND METHODS: Three samples of pigmented skin neoplasms were taken during surgical treatment in patients at the Blokhin National Medical Research Center of Oncology: two samples of Reed nevus (from a 9-year-old girl and a 15-year-old boy) and a sample of cutaneous melanoma that had developed in an 8-year-old boy. The materials were presented by paraffin blocks. Immunohistochemical staining was performed using antibodies against cyclin D1, p16INK4a, and HLA class I antigens. RESULTS: Differences were found between nevus and melanoma in the expression of all three markers. Thus, the nuclear expression of cyclin D1, a proliferation activator, occurred in some cells in the nevus samples and in the vast majority of cells in the melanoma samples. The nuclear expression of the cell cycle inhibitor p16INK4a was dramatically reduced in melanoma compared to nevus. HLA class I antigens were detected on the surface of individual nevus cells, but were completely absent on the membranes and in the cytoplasm of melanoma cells, which could promote the evasion of this tumor from the body's immunological supervision. CONCLUSION: Immunohistochemical test for the proteins cyclin D1, p16INK4a, and HLA class 1 antigens is a promising approach to differentially diagnosing between Reed nevus and cutaneous melanoma in children and adolescents.

[The use of intralaboratory and external quality control of immunohistochemical studies to improve the detection of estrogen and progesterone receptors]. / Primenenie vnutrilaboratornogo i vneshnego kontrolya kachestva immunogistokhimicheskikh issledovanii dlya uluchsheniya vyyavleniya retseptorov estrogenov i progesteronov.

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

[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.

[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.

[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.

[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.

[HER2/neu gene amplification as a mechanism of clonal heterogeneity in breast cancer]. / Amplifikatsiia gena HER2/neu kak mekhanizm vozniknoveniia klonal'noi geterogennosti pri rake molochnoi zhelezy.

OBJECTIVE: To estimate the heterogeneity of HER2/neu gene amplification in HER2/neu-positive breast cancer (BC). MATERIAL AND METHODS: Fluorescence in situ hybridization (FISH) assay was used to estimate HER2/neu gene amplification and HER2/CEP17 ratios in BC samples with an immunohistochemical evaluation of HER2/neu2+ expression. The results were interpreted according to the 2018 ASCO/CAP guidelines. BC samples with HER2/neu gene amplification (n = 25) was evaluated for variability in HER2/neu amplification and HER2/CEP17 ratios in 20 tumor cells counted using the FISH assay. RESULTS: Significant intratumoral variability was found in the HER2/neu gene copy number and HER2/CEP17 ratios. HER2/neu-negative cells (5-15%) were present in 28% of the examined samples found to be HER2/neu positive. The HER2/neu gene copy number and HER2/CEP17 ratios for these tumors were statistically significantly lower than those in the group in which all the counted cells were characterized by HER2/neu amplification: 6.25 (95% CI 4.3-12.45; p=0.0166) and 2.37 (95% CI 2.06-3.43; p=0.0076), respectively. The threshold value of HER2/CEP17, at which cells without amplification were detected in HER2/neu-positive tumors, was 2.5. CONCLUSION: HER2/neu gene amplification in BC is extremely variable both within a single tumor and between the tumors of the same biological subtype. Amplification heterogeneity is statistically significantly more common in HER2/neu-positive BC with a HER2/CEP17 ratio <2.5 and may affect the outcome of the disease and also be important in the choice of treatment policy.

[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.

[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.