[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.

[Study of FGFR2 status in gastric cancer by immunohistochemistry and fluorescent in situ hybridization]. / Izuchenie statusa FGFR2 pri rake zheludka metodami immunogistokhimii i flyuorestsentnoi gibridizatsii in situ.

BACKGROUND: Assessment of FGFR2 status in gastric cancer is an important task, without clarification of which it is impossible to identify a cohort of patients in whom the best response to treatment with anti-FGFR2 drugs could be obtained. OBJECTIVE: To conduct a comparative analysis of the expression and amplification of the FGFR2 gene in gastric cancer in primary tumors and metastases in the lymph nodes. MATERIAL AND METHODS: FGFR2 status was studied in 61 patients with stage III gastric adenocarcinoma using an immunohistochemical method (Abcam clone EPR24075-418, R&D clone 98706, Santa Cruz clone C-8, Abcam clone 1G3) and FISH. RESULTS: The antibody Abcam clone EPR24075-418 was found satisfactory for the immunohistochemical study of FGFR2. FGFR2 expression was detected in 26 (43%) cases, amplification in 5 (8%) cases. Amplification of FGFR2 in 4 cases out of 5 was accompanied by the expression of 3+, in 1 case - 2+. Discordance between FGFR2 expression in primary tumor and lymph node metastases was revealed in 13 (21%) cases. CONCLUSION: Clone EPR24075-418 showed the best result in assessing the expression of FGFR2: the correlation with FISH results in reaction 3+ was 100%. Due to the high heterogeneity of FGFR2 expression, it is recommended to either examine the material of the primary tumor and metastasis, or evaluate a large volume of the primary tumor.

[Gastric cancer with impaired DNA unpaired nucleotide repair system]. / Rak zheludka s narusheniem sistemy reparatsii nesparennykh nukleotidov DNK.

This article presents a case of successful treatment of inoperable gastric cancer with impaired mismatched nucleotide repair system (dMMR/MSI-H) in a 72-year-old patient. In view of age, somatic status and the presence of comorbidity, it was decided to prescribe anti-PD-1 therapy in the 1st line of treatment. Currently, after a 2-year course of treatment, the patient is in stable remission.

[Hormone-associated properties and plasticity of omental fat: the relation with clinical-morphological features of endometrial cancer in patients with different obesity phenotypes].

The authors aimed to compare expression of UCP1, aromatase (CYP19), markers of macrophage infiltration (CD68, CD163), omentin and PTEN in omental fat of endometrioid or non-endometrioid endometrial cancer (EC) patients with signs of standard (SO) or metabolically healthy obesity (MHO) by immunohistochemical (IHC) or real-time PCR methods. Totally 57 omental fat samples collected during surgery in EC pts (average age 60.1) were studied. According to IHC data, statistically significant decrease in expression of aromatase and CD68 was revealed in omental fat of MHO patients. Expression of UCP1 demonstrated an inclination to decrease in the same group, simultaneously showing correlation with clinical stage of EC. According to real time PCR data, omentin expression displayed tendency to an increase with increase in body mass index (whole group), clinical stage of EC (in SO subgroup) and serum omentin level (MHO subgroup). No any difference in studied omental fat parameters was discovered between patients with endometrioid and non-endometrioid EC. Thus, omental fat properties in EC patients are associated with obesity phenotype and not with histologic subtype of this cancer. Apparently, the features of omental fat depot characteristic for visceral adipose tissue at least are equal to its attributes as a brown fat compartment. Decrease, according to IHC info, of the estrogen biosynthesis and macrophagal infiltration in omental fat of EC patients with MHO phenotype may indicate additional mechanisms for more favorable in this case clinical course of uterine body cancer. Supported by RFBR grant 15-04-00384.

[The immunohistochemical features of ovarian serous adenocarcinoma cells, which determine a disease course and survival rates in patients].

OBJECTIVE: To study a relationship of survival rates to the expression of major genes (p53, PTEN, COX2, pRb and others) involved in the pathogenesis of ovarian cancer. SUBJECTS AND METHODS: The trial enrolled 23 patients with Stages III-IV ovarian serous adenocarcinoma. Of them, 11 patients showed a long overall survival (median 50 ± 2.5 months), 12 did a short one (14.5 ± 0.7 months). Ovarian adenocarcinomas were high- and low-grade in 20 (87%) and 3 (13%) cases, respectively. RESULTS: Estimating the relationship of the expression of the examined markers and the prognosis of the disease showed that the expression of p53 and Rb was more common in the patients with a short overall survival (median 14.5 versus 50 months; p = 0.03; p = 0.04). CONCLUSION: The expression of mutant p53 protein and that of retinoblastoma (Rb) gene protein are poor prognostic factors for ovarian serous adenocarcinoma.

[A case of Richter's syndrome].

The paper provides a morphological and immunohistochemical account of diffuse large B-cell lymphoma developing in a patient with chronic lympholeukemia--Richter's syndrome. There is a mismatch between the histological and cytological structure of a tumor in the bone marrow and lymph node.

[Positron emission tomography with 18F-FDG compared with proliferative activity of tumor cells in different subtypes of non-Hodgkin lymphoma].

In the course of this study we determined the ability of positron emission tomography (PET) with the 18F-FDG to detect non-hodgkin lymphoma lesions, assess their proliferative activity and differentiate aggressive tumors from indolent. Tracer uptake in lymphoma was evaluated semiquantitatively by calculation of standardized uptake values (SUV). It was compared with tumor grade and proliferation fraction determined by Ki-67 staining. In patients with indolent lymphoma, mean SUV was 2.5 +/- 0.6. In patients with aggressive lymphoma a significantly higher 18F-FDG uptake was observed (mean SUV was 8.1 +/- 1.3). Linear regression analysis indicated significant correlation of 18F-FDG uptake to biopsy samples proliferation fraction in patients with diffuse large B-cell lymphoma (r = 0.55, p = 0.05) and indolent non-Hodgkin's lymphoma (r = 0.7, p < 0.05). In this clinical study 18F-FDG uptake correlates with the aggressiveness of malignant lymphomas and with biopsy samples proliferative activity.

[The diffuse type of giant cell tumors of the tendon sheaths].

The authors give a morphological and immunohistochemical description of diffuse giant cell tumors of the tendon sheath, which differ in the composition of neoplastic cells. Immunohistological detection of CD68, HAM56, CD45, and lysozyme is of crucial importance in the differential diagnosis with malignant soft tissue tumors. Attention is drawn to the high proliferative activity of tumor cells; the Ki-67 index is as high as 40% in occasional portions, which may give a misimpression of malignancy.

[The place of dendritic cells in the microenviroment in Hodgkin's lymphoma].

Dendritic cells (DCs) are the least studied microenvironment elements in Hodgkin's lymphoma (HL). Ninety-five lymph nodes were morphologically and immunohistochemically studied in patients with classical HL. The authors found CDla- and langerin-positive DCs in the presence of T lymphocytes, which were localized in the close proximity to neoplastic Reed-Sternberg cells (RSCs). There were also CD23-positive follicular DCs, which were typically located at the periphery of tumor foci, in the areas of residual follicular structures, were surrounded by B lymphocytes and were rarely associated with RSCs. There were two morphologically distinct groups among the CD 1a- and langerin-positive DCs; one had developed cytoplasmic processes, which formed a network around the RSCs (probably a more mature/functionally active form); the other had round cells with short cytoplasmic processes, loosely distributed around the neoplastic cells (a less mature/active form). The function and role of CD1a- and langerin-positive DCs in HL call for further investigation. The topographic closeness of these DCs to RSCs suggests that these cells play a considerable role in the pathogenesis of HL.

[Monophasic angiomyolipoma (PEComa) of the liver].

The paper provides a morphological and immunohistochemical description of hepatic angiomyolipoma in a 29-year-old woman. Microscopically, it is a tumor with trabecular and diffuse growth patterns, which consists of polygonal cells with pleomorphic nuclei and extensive cytoplasm accumulated around the nucleus. Immunohistochemical study is of crucial importance in making the diagnosis. The tumor cells coexpress smooth muscle actin and the melanin markers: HMB-45, melan A, and MITF. The proliferative activity of the tumor is very low (Ki-67 index < 1%). According to the present views, angiomyolipoma belongs to perivascular epithelioid cell tumors (PEComas).

[Malignant vulvar soft tissue myoepithelioma].

The authors describe a case of malignant vulvar soft tissue myoepithelioma in a 41-year-old woman. Microscopically, epithelioid and spindle cells were located in the myxoid stroma. Tumor cells co-expressed pan-cytokeratin, EMA, and cytokeratin 18, vimentin, protein S100, and smooth muscle actin. The tumor was found to have a very high proliferative activity (Ki-67 was as high as 80%). The disease was fulminant with a fatal outcome 4 months after the occurrence of the first symptoms of the tumor.

[Epitheliod hemangioendothelioma of the lung].

The authors give a morphological and immunohistochemical description of epitheliod hemangioendothelioma of the lung in two women aged 62 and 74 years. Evident neovascularization capacity, a significant tumor cell intracytoplasmic lumen frequently packed with red blood cells, and positive immunohistochemical reactions to endothelial antigens are of prime importance in making its diagnosis.

[Galectin-3 in diagnosis of thyroid cancer].

Fourty patients with thyroid nodules were examined. Benchmarking study of FNA results, histology reports and immunohistochemistry of Galectin-3 expression were performed. Galectin-3 is a highly sensitive oncomarker for papillary carcinoma of thyroid gland: sensitivity--100%, specificity--71%, diagnostic value--85%.