The impact of MYD88 and PIM1 in mature large B-cell non-Hodgkin lymphomas: Defining element of their evolution and prognosis.

Sequence studies of the entire exome and transcriptome of lymphoma tissues have identified MYD88 and PIM1 as involved in the development and oncogenic signaling. We aimed to determine the frequency of MYD88 and PIM1 mutations, as well as their expressions in conjunction with the clinicopathological parameters identified in mature large B-cell non-Hodgkin lymphomas. The ten-year retrospective study included 50 cases of mature large B-cell lymphoma, diagnosed at the Pathology Department of the Emergency County Hospital of Constanta and Sacele County Hospital of Brasov. They were statistically analyzed by demographic, clinicopathological, and morphogenetic characteristics. We used a real-time polymerase chain reaction technique to identify PIM1 and MYD88 mutations as well as an immunohistochemical technique to evaluate the expressions of the 2 genes. Patients with lymphoma in the small bowel, spleen, brain, and testis had a low-performance status Eastern Cooperative Oncology Group (P = .001). The Eastern Cooperative Oncology Group performance status represented an independent risk factor predicting mortality (HR = 9.372, P < .001). An increased lactate dehydrogenase value was associated with a low survival (P = .002). The international prognostic index score represents a negative risk factor in terms of patient survival (HR = 4.654, P < .001). In cases of diffuse large B-cell lymphoma (DLBCL), immunopositivity of MYD88 is associated with non-germinal center B-cell origin (P < .001). The multivariate analysis observed the association between high lactate dehydrogenase value and the immunohistochemical expression of PIM1 or with the mutant status of the PIM1 gene representing negative prognostic factors (HR = 2.066, P = .042, respectively HR = 3.100, P = .004). In conclusion, our preliminary data suggest that the oncogenic mutations of PIM1 and MYD88 in our DLBCL cohort may improve the diagnosis and prognosis of DLBCL patients in an advanced stage.

CMV and HIV Coinfection in Women from a Region in Eastern Europe.

(1) Background: Human cytomegalovirus (CMV) infection is one of the most frequent opportunistic infections in immunosuppressed patients. Romania has one of the highest incidences of patients living with human immunodeficiency virus (HIV) which determines an immunosuppressive state. The aim of this study was to establish the prevalence of CMV infection among women living with HIV in Southeastern Romania and also to evaluate and correlate antiretroviral therapy (ART) with CD4 level and CMV disease evolution. (2) Methods: Seventy women living with HIV from Southeastern Romania were screened for CMV infection using antigen quantification. Of these, 50 were included in the study. First, the patients filled out a questionnaire regarding social conditions and other associated diseases. Then, we explored the statistical correlations between the data and HIV status, CD4+ cell counts, viral load, and antiretroviral therapy (ART). (3) Results: Median age of the patients was 33 years. Twenty-nine cases were diagnosed with HIV after sexual life beginning and 21 before. Most of the patients had a CD4 level over 200 cells/µL. ART duration in the CD4 under 200 cells/µL group was a bit longer than that in the CD4 over 200 cells/µL group. Forty-one patients had undetectable viremia. CD4 average value in the lot of patients with undetectable viremia was 704.71 cells/µL and in the lot with detectable viremia was 452.44 cells/µL. Viremia values correlated negatively with CD4 level. A positive correlation between IgG CMV values and ART therapy length was identified. A negative significant correlation between values of IgG CMV and values of CD4 was identified. CD4 value correlated negatively with IgG CMV values and with CMV avidity. (4) Conclusions: IgG CMV values had a weak positive correlation with ART therapy length, and a negative statistically significant correlation with values of CD4. CMV avidity has a negative correlation with CD4 value.

A retrospective study of nonneoplastic and neoplastic disorders of the salivary glands.

The spectrum of major and minor salivary gland disorders varies widely. Epidemiological data on some injury categories are rare and often not up-to-date. This study aims to analyze epidemiological data using clinical, paraclinical, and histopathological parameters. Study was carried out for 5 years on the nonneoplastic and tumoral pathology of the salivary glands. Data were statistically analyzed using the appropriate parameters. Data analysis according to the biological behavior of the lesions revealed great heterogeneity. Statistically significant correlations were observed between the type of injury, age (P = .002) and gender (0.033). The environment of origin of the patients as well as the comorbidities reflected in most cases the nature of the process. Associations were also observed between the biological behavior of the lesions and the hemicranial topography (P = .019), the type of salivary gland (P = .024), and the surgical technique used (P < .001). Most cases were identified in the major salivary glands, often in the parotid. The most common diseases are represented by nonspecific chronic sialadenitis (nonneoplastic lesion), pleomorphic adenoma and Warthin tumor (benign tumors), mucoepidermoid carcinoma (malignant tumor), and squamous carcinoma (secondary tumor). They presented axial diameters between 2 to 95 mm. The most used curative technique was subtotal excision with facial nerve preservation. In conclusion, the study highlighted the main epidemiological aspects of salivary gland disorders. Some data agree with the specialty literature, and particular aspects are also observed. Therefore, this research is useful both in the medical and research fields.

NET G3 vs NEC: p53 and Rb1 Immunolabeling in High-grade Gastrointestinal Neuroendocrine Neoplasms - Is It Enough for the Differential Diagnosis?

BACKGROUND AND AIMS: High-grade gastrointestinal neuroendocrine neoplasms (GI-NENs) are divided into well-differentiated G3 neuroendocrine tumors (NETs G3) and neuroendocrine carcinomas (NECs), having identical cut-offs of proliferation, but different biomolecular origins. This translates in distinct treatment choices. Our aim was to establish if p53/Rb1 immunohistochemical status in GI-NENs with Ki67 index >20% can predict the histopathological diagnosis. METHODS: p53/Rb1 immunolabelling was performed on 42 cases of high-grade GI-NENs, diagnosed as NET G3, NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) with NEC component. Immunolabeled slides were digitally scanned, with automatic quantification of p53 and Rb1, blind to the diagnosis. RESULTS: The p53 positive percentage was stratified; two cut-offs were selected, naming the intervals as N (null, <1%), T (tumor, 1%-20%) and C (carcinoma, >20%). The Rb1 expression loss in >90% of neoplastic cells was considered mutational. NETs G3 mainly showed the T status (14/16, 87.5%), followed by N (1/16, 6.25%) and C (1/16, 6.25%); NECs and NEC components in MiNENs predominantly expressed the C status (19/26, 73.08%), followed by N (5/26, 19.23%) and T (2/26, 7.69%) (p<0.001, χ 2 =27.017). NET G3s showed positive expression for Rb1; 73.08% of NECs expressed negative Rb1 (p<0.001, χ 2 =21.351). NECs and NEC components in MiNENs showed Rb1 mutational status in 13 C cases (13/19, 68.42%), 4 N cases (4/5, 80%) and in both the T cases (p=0.002, χ 2 =11.187). CONCLUSIONS: Our results highlight the correlations between the p53/Rb1 immunostainings and the histopathological diagnosis of high-grade GI-NENs. NECs and NEC components in MiNENs showed a p53 mutational status (0% or 21-100%) and predominantly negative Rb1 expression. NETs G3 showed a p53 wild-type status (1-20%) and retained Rb1 expression. These findings suggest that the differential diagnosis of high-grade GI-NENs may benefit from p53/Rb1 immunohistochemical tests in everyday practice.

The Role of Pathogenesis Associated with the Tumor Microclimate in the Differential Diagnosis of Uterine Myocytic Tumors.

Myocytic tumors of the uterus present vast morphological heterogeneity, which makes differential diagnosis between the different entities necessary. This study aims to enrich the existing data and highlight new potential therapeutic targets regarding aspects related to the pathogenic process and the tumor microenvironment in order to improve the quality of life of women. We performed a 5-year retrospective study, including particular cases of uterine myocyte tumors. Immunohistochemical analyses of pathogenic pathways (p53, RB1, and PTEN) and tumor microclimate using markers (CD8, PD-L1, and CD105), as well as genetic testing of the PTEN gene, were performed. The data were statistically analyzed using the appropriate parameters. In cases of atypical leiomyoma, a significant association was observed between PTEN deletion and an increased number of PD-L1+ T lymphocytes. For malignant lesions and STUMP, PTEN deletion was associated with the advanced disease stage. Advanced cases were also associated with an increased mean CD8+ T cell count. An increased number of lymphocytes was associated with an increased percentage of RB1+ nuclei. The study corroborated clinical and histogenetic data, highlighting the importance of the differential diagnosis of these tumors to improve the management of patients and increase their quality of life.

Tissue and Circulating MicroRNA-31, MicroRNA-200b, and MicroRNA-200c Reflects Disease Activity in Crohn's Disease Patients: Results from the BIOMIR Study.

BACKGROUND AND AIMS: MicroRNAs (miR) have altered expression in multiple autoimmune disorders including inflammatory bowel disease. The aim of the study was to assess the tissue and circulating miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for intestinal disease activity in patients with Crohn's disease (CD). METHODS: The study included 45 patients with histopathological confirmed CD and active disease (defined as fecal calprotectin >50 µg/g and Simple Endoscopic Score (SES) of CD >3), and 21 subjects as controls for the validation cohort. Demographic and clinical data, biomarkers (fecal calprotectin), endoscopy data, the expression levels of miR-31, miR-200b, and miR-200c in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic analysis was performed to assess the miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for active CD. RESULTS: Mean fecal calprotectin was 1540±890 µg/g. Mean SES-CD was 8.9±4.2. Tissue and circulating miR- 31 were significantly correlated with fecal calprotectin (r=0.81, r=0.83, p<0.01) and with SES-CD (r=0.82, r=0.79, p<0.01). The expression level of miR-31 was significantly upregulated in CD tissue cases compared to the control tissue samples (6.24±1.57 vs. 3.70±1.44; p <0.01). Similarly, serum miR-31 expression levels in CD patients were significantly upregulated compared to the control serum samples (0.78±0.42 vs. -2.07±1.00; p<0.01). The expression levels of tissue miR-200b and miR-200c were significantly upregulated in CD tissue cases compared to the control tissue samples (-5.25±0.93 vs. -4.69±0.80, p=0.03 for miR-200b, and -0.86±0.96 vs. 0.39±0.66, p<0.01 for miR-200c). Similarly, serum miR-200b and miR-200c expression levels in CD patients were significantly upregulated compared to the control serum samples (p < 0.05). Receiver operating characteristic analysis revealed that the expression levels of the selected miRNAs could help to discriminate active CD patients from healthy controls with very good specificity and sensitivity. CONCLUSIONS: Tissue and circulating miR-31, miR-200b, and miR-200c reflect disease activity in CD patients and can be used as biomarkers for active disease.

TCF7L2, CASC8, and GREM1 polymorphism and colorectal cancer in south-eastern Romanian population.

Colorectal cancer (CRC) is a heterogeneous disease with an increasing trend and with multiple epigenetic alterations and different molecular features, a major cause of mortality and morbidity. The Wnt/ß-Catenin pathway is involved in multiple aspects of cell dynamics, architecture of developing gastrointestinal tissues, and intestinal tissue homeostasis in adults, but its aberrant activity plays an important role in every aspect of colorectal carcinogenesis. The aim of our study was to investigate the association of the TCF7L2 rs7903146, CASC8 rs6983267, and Gremlin1 (GREM1) rs16969681 polymorphism in patients with CRC without other pathologies. A case-control study conducted on 31 patients diagnosed with CRC and 30 healthy controls age and sex-matched with the patients. Real time PCR was used to determine the genotypes of rs7903146, rs698267, rs1696981. We observed no association between rs6983267 and rs16969681 polymorphism and risk of CRC and low association between TCF7L2, rs7903146, polymorphism and risk of CRC. The recessive model of the TCF7L2 rs7903146 had an OR of 1.6 (95% CI 0.058-4.414, P < .05) which means that TT genotype increased the risk and possibility of development of CRC. Our study did not confirm a significant association between TCF7L2 rs7903146, CASC8 rs6983267, and GREM1 rs16969681 with CRC, but emphasizes the possibility of existence of a high risk of CRC development in patients with TT genotype of rs7903146.

Diffuse large B cell lymphoma CD5-positive arising in an immune deficiency and immune dysregulation setting: A case report and brief review of the literature.

RATIONALE: In the era of antiretroviral therapy, lymphoma is the primary cause of cancer-related death among human immunodeficiency virus (HIV)-infected people and the most prevalent and aggressive non-Hodgkin lymphoma is diffuse large B cell lymphoma, which usually has an aggressive clinical course. CD5-positive diffuse large B cell lymphoma (DLBCL) is an insufficiently studied, relatively new entity, which accounts for 5% to 10% of the DLBCL population. The current study presents the clinicopathological features, diagnostic approach, and clinical outcomes of this HIV-related lymphoma and highlights the importance of the early diagnosis of CD5-positive DLBCL. PATIENT CONCERNS: We present a case of a 30-year-old male patient, with a medical history of HIV-positive serology and antiviral treatment, presenting with diffuse abdominal pain and symptoms related to obstruction or perforation, followed by exploratory laparotomy and surgical resection of the small intestine with other areas of involvement. The surgical specimen was morphologically evaluated and immunohistochemical stained. DIAGNOSES AND INTERVENTIONS: Histopathologic examination revealed a diffuse neoplastic proliferation of large B lymphocytes within the small intestine, lacking features of other defined types of large B cell lymphoma. The diagnosis of CD5-positive DLBCL subtype was made after immunostaining with twelve monoclonal antibodies (CD3, CD5, CD10, CD20, CD23, CD30, CD68, Cyclin D1, MUM1, Bcl2, Bcl6, and Ki-67). The expression profile of immunohistochemical markers (CD10, Bcl6, and MUM1) established the cell of origin of this case of DLBCL by using the Hans algorithm. LESSONS: The current report highlights the importance of early diagnosis of CD5-positive DLBCL because of its poor prognosis and calls attention to the critical importance to identify immunodeficiencies because doing so affects the types of treatments available. Although cell-of-origin is useful for predicting outcomes, the germinal center B cell like and activated-B cell like subtypes remain heterogeneous, with better, and worse prognostic subsets within each group.

Proteomics and genomics of a monomorphic epitheliotropic intestinal T-cell lymphoma: An extremely rare case report and short review of literature.

RATIONALE: Monomorphic epitheliotropic intestinal T-cell lymphoma, formerly known as enteropathy-associated T-cell lymphoma, is an extremely rare, aggressive peripheral extranodal T-cell lymphoma, that is infrequent in native European and Caucasian populations. The current study presents the clinicopathological features, diagnostic approach, and clinical outcomes of this rare entity of lymphoma and highlights the importance of the early diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). PATIENT CONCERNS: Main symptoms and/or important clinical findings: We present the case of a 69-year-old male patient presenting with an abdominal mass, intestinal transit disorder, and weight loss. The abdominal computed tomography (CT) revealed features suggestive of a malignancy. Following clinical and imaging investigations, surgical resection of the small intestine with other areas of involvement has been performed and further to the histopathological examination and immunohistochemical testing are mandatory. DIAGNOSES AND INTERVENTIONS: Histopathological evaluation of the tumor revealed a proliferation of medium- to large-sized monomorphic lymphocytes, with vesicular nuclei, prominent nucleoli, and a moderate amount of clear to pale eosinophilic cytoplasm, with an association of infrequent Reed-Sternberg-like cells. Immunohistochemical assessment of the aforementioned tumor using CD3, CD8, CD5, CD20, and CD30 confirmed the T cell proliferation line and the monomorphic epitheliotropic intestinal T-cell lymphoma diagnosis. LESSONS: The current report highlights the importance of early diagnosis of MEITL owing to its poor prognosis and presents histopathological features that help distinguish MEITL from inflammatory bowel diseases and less aggressive T-cell lymphomas.

Implications of Cellular Immaturity in Necrosis and Microvascularization in Glioblastomas IDH-Wild-Type.

Necrosis and increased microvascular density in glioblastoma IDH-wild-type are the consequence of both hypoxia and cellular immaturity. Our study aimed to identify the main clinical-imaging and morphogenetic risk factors associated with tumor necrosis and microvascular in the prognosis of patient survival. We performed a retrospective study (10 years) in which we identified 39 cases. We used IDH1, Ki-67 and Nestin immunomarkers, as well as CDKN2A by FISH. The data were analyzed using SPSS Statistics. The clinical characterization identified only age over 50 years as a risk factor (HR = 3.127). The presence of the tumor residue, as well as the absence of any therapeutic element from the trimodal treatment, were predictive factors of mortality (HR = 1.024, respectively HR = 7.460). Cellular immaturity quantified by Nestin was associated with reduced overall survival (p = 0.007). Increased microvascular density was associated with an increased proliferative index (p = 0.009) as well as alterations of the CDKN2A gene (p < 0.001). CDKN2A deletions and cellular immaturity were associated with an increased percentage of necrosis (p < 0.001, respectively, p = 0.017). The main risk factors involved in the unfavorable prognosis are moderate and increased Nestin immunointensity, as well as the association of increased microvascular density with age over 50 years. Necrosis was not a risk factor.

Influence of type II diabetes mellitus on postoperative complications following colorectal cancer surgery.

Diabetes mellitus (DM) promotes colorectal cancer (CRC) carcinogenesis through complex processes and is considered as an independent risk factor for cancer in general and for CRC in particular. Diabetic patients have complications in the postoperative period following CRC surgery. The aim of the present study was to explore the effect of type II DM (T2DM) on postoperative outcomes for CRC compared with non-diabetic patients. The present study analyzed the data from patients admitted to the General Surgery Department, Emergency Hospital of Constanța (Romania) diagnosed with CRC and DM compared with a control group (patients with CRC, without DM, recruited in the same period and frequency matched to cases by number, sex and age) analyzing patient comorbidities and postoperative complications. A total of 61 patients had undergone surgery for CRC and met the inclusion criteria in the present study conducted during September 2020-2021. A total of 30 patients associated T2DM. Diabetic patients have been associated with more comorbidities than non-diabetics; the age-adjusted Charlson comorbidity index score ≥6 was identified in 90% of diabetic patients compared with 45.2% of controls. Grade III Clavien-Dindo classification was observed in 13.3% diabetic patients compared with 3.2% of non-diabetic patients. Additionally, a higher rate of urinary and pulmonary complications (6.7 vs. 3.2% in controls respectively) in patients with diabetes was found. Postoperative hospitalization was prolonged in diabetic patients (P=0.042). Univariate and multivariate analyses revealed that the laparoscopic approach for diabetic patients was found to be associated with

Association of TCF7L2, CASC8 and GREM1 Polymorphisms in Patients with Colorectal Cancer and Type II Diabetes Mellitus.

BACKGROUND: The aim of the study is to explore the association between the TCF7L2 rs7903146, CASC8 rs6983267 and GREM1 rs16969681 polymorphisms in patients diagnosed with type 2 diabetes mellitus (T2DM) and colorectal cancer. METHODS: Sixty individuals were enrolled in this case-control study: thirty with colorectal cancer and type II diabetes mellitus (T2DM) and thirty healthy control individuals. Real-time PCR was used to determine the genotypes of TCF7L2 rs7903146, CASC8 rs 6983267 and GREM1 rs16969681 in patients with CRC and T2DM and in patients without T2DM and CRC. The Hardy-Weinberg equilibrium was determined in the control group for the genotype distribution of every polymorphism. RESULTS: People carrying the TT genotype of rs7903146, rs6983267 and rs1696981 had a significant association with T2DM and CRC. Moreover, the people with the TT genotype of rs1696981 had a greater risk for T2DM and CRC (OR = 7, CI 0.397-23.347). CONCLUSIONS: TCF7L2 rs7903146, CASC8 rs6983267 and GREM1 rs16969681 could be risk factors for the association of T2DM with CRC.

Characterization of the Tumor Microenvironment and the Biological Processes with a Role in Prostatic Tumorigenesis.

Prostate intratumoral heterogeneity, driven by epithelial−mesenchymal plasticity, contributes to the limited treatment response, and it is therefore necessary to use the biomarkers to improve patient prognostic survival. We aimed to characterize the tumor microenvironment (T lymphocyte infiltration, intratumoral CD34, and KI-67 expressions) by immunohistochemistry methods and to study the biological mechanisms (cell cycle, cell proliferation by adhesion glycoproteins, cell apoptosis) involved in the evolution of the prostate tumor process by flow-cytometry techniques. Our results showed that proliferative activity (S-phase) revealed statistically significant lower values of prostate adenocarcinoma (PCa) and benign prostatic hyperplasia (BPH) reported at non-malignant adjacent cell samples (PCa 4.32 ± 4.91; BPH 2.35 ± 1.37 vs. C 10.23 ± 0.43, p < 0.01). Furthermore, 68% of BPH cases and 88% of patients with PCa had aneuploidy. Statistically increased values of cell proliferation (CD34+ CD61+) were observed in prostate adenocarcinoma and hyperplasia cases reported to non-malignant adjacent cell samples (PCa 28.79 ± 10.14; BPH 40.65 ± 11.88 vs. C 16.15 ± 2.58, p < 0.05). The CD42b+ cell population with a role in cell adhesion, and metastasis had a significantly increased value in PCa cases (38.39 ± 11.23) reported to controls (C 26.24 ± 0.62, p < 0.01). The intratumoral expression of CD34 showed a significantly increased pattern of PCa tissue samples reported to controls (PCa 26.12 ± 6.84 vs. C 1.50 ± 0.70, p < 0.01). Flow cytometric analysis of the cell cycle, apoptosis, and adhesion glycoproteins with a critical role in tumoral cell proliferation, T cell infiltrations, Ki-67, and CD 34 expressions by IHC methods are recommended as techniques for the efficient means of measurement for adenocarcinoma and hyperplasia prostate tissue samples and should be explored in the future.

HPV and HIV Coinfection in Women from a Southeast Region of Romania-PICOPIV Study.

Background and Objectives: Romania faces one of the highest cervical cancer burdens in Europe though it is a preventable cancer through population screening by cytology and human papillomavirus (HPV) detection. Also, it has one of the highest incidences of human immunodeficiency virus (HIV) infection. HPV and HIV coinfection are frequently encountered. The aim of study was to establish the prevalence of HPV infection among HIV-positive women in Southeast Region of Romania, to genotype high risk HPV types -and to correlate the results with clinical data and cytological cervical lesions. Materials and Methods: 40 HIV-positive women were screened for HPV types and for cytological cervical lesions. The findings were evaluated in correlation with CD4 cell counts, HIV viral load, age at first sexual intercourse, number of sexual partners, vaginal candidiasis, and Gardnerella using statistical methods. Results: 19/40 (47.5%) women were positive for HPV types, 63.15% infected with single HPV type and 36.85% with multiple HPV types. The most frequent types were type: 31 (42.1%), 56 (31.57%), 53 (15.78%). On cytology, 34 (85%) women were found with NILM of which 38.23% were HPV-positive. Fifteen percent of women had abnormal cytology (three ASC-US, three LSIL), and all of them were HPV-positive. Through analyzing the value of CD4 count, women with CD4 count ≤ 200 cells/µL were found to be significantly more likely to be infected with HPV; meanwhile there was no correlation between the detection of HPV types and HIV viral load. Candida or Gardnerella were more often associated with HIV-positive women with HPV, than in women without HPV. Conclusions: Infection with HPV types is common among HIV-positive women in the Southeast Region of Romania and it is associated with age at the beginning of sexual life, number of sexual partners, CD4 value, vaginal candidiasis, and Gardnerella infection.

Dinosaur Tail Appendix in Trisomy 13.

BackgroundAmong the many malformations associated with trisomy 13, one of the less recognized is dinosaur tail appendix. Case report: We illustrate a dinosaur-tail appendix from an autopsy in a newborn female with trisomy 13. This malformation has a frequency between 0.014% and 3.7% in general population. Conclusion: Trisomy 13 is a relatively well-known chromosomal disorder in which dinosaur tail appendix can be found. This entity should be considered element of a complete morphological diagnosis.

Assessment of programmed death-ligand 1 receptor immunohistochemical expression and its association with tumor-infiltrating lymphocytes and p53 status in triple-negative breast cancer.

Breast cancer (BC) is the second most frequent type of cancer for both sexes combined, after lung cancer. Triple-negative BC (TNBC) molecular subtype is characterized by lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) immunoexpression or amplification and represent 10-20% of all BC cases. The issue of the present study was to analyze the associations between programmed death-ligand 1 (PD-L1) immunoexpression and distribution of stromal tumor-infiltrating lymphocytes (stTILs) combined with clinico-morphological features of patients with TNBC. Secondly, our research evaluated PD-L1 immunoexpression as a prognostic factor and its correlation with p53 immunoexpression. Thirty cases with primary TNBC without prior neoadjuvant therapy were included in this research. stTILs were identified in all cases, most of them with low distribution (66.7%). A positive immunoreaction for PD-L1 was observed in 40% of cases. The PD-L1 immunoexpression was statistically significant associated with age, pathological tumor size, lymphovascular invasion, stTILs level, the presence of cluster of differentiation 8-positive (CD8+) TILs and p53 immunoexpression. In the present study, a positive PD-L1 immunoexpression was associated with a worse distant metastasis free survival (DMFS). We also found not only that high stTILs level were associated with a better DMFS but also that there was a statistically significant association between stTILs level and PD-L1 immunoexpression. Our results bring new insights to the fine connections between tumor microenvironment and molecular changes of TNBC. It helps us to better understand these aggressive tumors to identify the more useful biomarkers for predicting the response to adjuvant therapy and can represent a method for selecting the most suitable patients for immunotherapy.

Biomarkers involved in evaluation of platelets function in South-Eastern Romanian patients with hematological malignancies subtypes.

ABSTRACT: At present, various researches presented how subtypes of hematological malignancies are related to stages of the immune response, because the activated immune system represents a promising form in cancer treatment. This study explores the relationship between the adaptive immune system (T cells), and the coagulation system (platelets, platelet membrane glycoproteins, platelets derivate microparticles) which seems to play an important role in host immune defense of patients with acute myeloblastic leukemia (AML) or B cell lymphoma (BCL), 2 of the most common hematological malignancies subtypes.Blood samples (n = 114) obtained from patients with AML or BCL were analyzed for platelet membrane glycoproteins (CD42b, CD61), glycoprotein found on the surface of the T helper cells (CD4+), protein complex-specific antigen for T cells (CD3+), platelet-derived microparticles (CD61 PMP) biomarkers by flow cytometry, and hematological parameters were quantified by usual methods.In patients with AML, the means of the percentage of the expressions of the molecules on platelet surfaces (CD61 and CD42b, P < .01; paired T test) were lower as compared to both control subgroups. The expression of cytoplasmic granules content (CD61 PMP) had a significantly higher value in patients with AML reported to controlling subgroups (P < .01; paired T test), which is suggesting an intravascular activation of platelets.The platelet activation status was presented in patients with low stage BCL because CD61 and CD42b expressions were significantly higher than control subgroups, but the expression of CD 61 PMP had a significantly decreased value reported to control subgroups (all P < .01; paired T test). T helper/inducer lineage CD4+ and T lymphoid lineage CD3+ expressions presented significant differences between patients with AML or low stage BCL reported to control subgroups (all P < .01; paired T test).Platelet-lymphocyte interactions are involved in malignant disorders, and CD61, CD42b present on platelet membranes, as functionally active surface receptors mediate the adhesion of active platelets to lymphocytes, endothelial cells, and cancer cells.

Molecular profiling of the colon cancer in South-Eastern Romania: Results from the MERCUR study.

ABSTRACT: Colorectal cancer is a heterogeneous disease with multiple epigenetic alterations and different molecular features. The molecular classification is based on 2 major distinct pathways: microsatellite stable pathway and the microsatellite instability pathway. Molecular profiling of colorectal cancer provides important information regarding treatment and prognosis. Aim of the study was to assess the frequency of microsatellite instability in colon cancer and the clinicopathological characteristics of the tumors with high level of microsatellite instability (MSI-H) in our region. The secondary outcome was to assess the frequency of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in colon cancer.The study included 129 patients with colon cancer fit for surgery. Demographic data, clinical and pathological data, immunohistochemistry staining pattern (4 mismatch repair proteins were investigated), and BRAF gene mutations were assessed. According to microsatellite instability status by polymerase chain reaction, patients were divided into 3 groups: microsatellite stable (MSS) = 108 patients, high level of microsatellite instability (MSI-H) = 15 patients and low level of microsatellite instability (MSI-L) = 6 patients. Different clinicopathological comparisons between MSS and MSI-H patients, and between MSS and MSI-L patients were performed.Microsatellite instability was found in 16.3% patients: 11.6% had MSI-H and 4.7% had MSI-L. Significantly more patients in the MSI-H group than in the MSS group were female (P = .01) and had a family history of colon cancer (P < .001). MSI-H and MSI-L groups were associated with the ascending colon location of the tumors, were mostly type G3, T2, and stage I whereas MSS tumors were mostly G2, pT3, and stage III. Overall, BRAF mutations were identified in 18/129 patients (13.9%). BRAF mutant tumors were predominantly associated with MSI-H and MSI-L tumors. Immunohistochemistry had a sensitivity of 76% and a specificity of 89% in detecting MSI tumors and an accuracy of 87.6%.The frequency of microsatellite instability in our study was 16.3%. MSI-H is a distinct molecular phenotype of colon cancer with particular features: female gender, family history of colorectal cancer, a predilection for the ascending colon, poorly differentiated, predominantly T2, and stage I. The frequency of BRAF mutations was 13.9% and mutations were more often present in the MSI tumors.

Genetic Antibiotic Resistance of Helicobacter pylori in South-Eastern Romania.

BACKGROUND AND AIM: Helicobacter pylori infection is very common worldwide, and it is associated with an important gastric pathology. Treatment of this infection is difficult and consists of the combination of two or three antibiotics. However, the rate of resistance to treatment is high. Antimicrobial resistance of Helicobacter pylori is based on its cultivation in the laboratory and testing of phenotypic susceptibility, a time-consuming, laborious method. This study aimed to detect the genetic resistance to antibiotics of Helicobacter pylori in the south-eastern region of Romania. METHODS: Ninety patients with positive rapid urease test gastric biopsy samples were tested. Genetic resistance to antibiotics (fluoroquinolone and clarithromycin) was tested by GenoType HelicoDR kit (Hain Lifescience GmbH, Germany). RESULTS: Clarithromycin resistance mutations were detected in 20% of patients, the commonest mutation in our study beeing A2147G (associated with high level of clarithromycin resistance and lower cure rates). Fluoroquinolones resistance mutations were detected in 30% of patients, and the most common mutations were D91N, D91G, and N87K. There was no correlation with patients gender or age, with the exception of fluoroquinolone resistance, which was detected more frequently in females.   Conclusions. Clarithromycin and fluoroquinolone resistance of Helicobacter pylori is moderately high in our study. There is a need for monitoring Helicobacter resistance patterns in Romania to provide data that can guide empirical treatment. This is the first published study on the genetic resistance of Helicobacter pylori in Romania.

A boy with 13.34-Mb interstitial deletion of chromosome 4p15: A new case report and review of the literature.

RATIONALE: To date, >40 cases have been described with interstitial deletions involving the 4p15 region. PATIENT CONCERNS AND DIAGNOSIS: We report a case of a 3-year-old boy with an interstitial de novo deletion of approximately 13.34 Mb in 4p15.1-15.31 having mild developmental delay and multiple minor congenital abnormalities. LESSONS: This case presents a clinical manifestation that is similar but not identical to other reported cases. In this report, we have provided a detailed description of a 3-year-old patient with an interstitial 4p deletion and mildly affected phenotype. We discuss the possible involvement of SLIT2, KCNIP4, and LGI2 in cortical development and RBPJ in skeletal abnormalities.