Negative Bcl-2 Research Articles

Association of Cellular Cannibalism with Immunohistochemical Expression of CD31, CD68 and BCL2 in Oral Squamous Cell Carcinoma: An Observational Study.

Cellular cannibalism (CC) is a prime metabolic event to determine the aggressive potential of oral squamous cell carcinoma (OSCC). However, the etiology and mechanism behind this degradation are still ambiguous. The aim of the study was to explore the etiopathogenetic mechanism behind CC, along with its association with degree of differentiation, angiogenic, phagocytic and antiapoptotic activity in OSCC. Seventy-three tissue sections of various histological grades of OSCC were retrieved from departmental archives and scanned for cannibalistic cells. Immunohistochemical analysis using CD31, CD68, and BCL2 was performed. The data obtained were analyzed using Chi-square, Spearman's correlation test and multiple regression analysis (p < 0.05). CCs were present significantly in various grades of OSCC (p < 0.00). Immunohistochemical analysis revealed a significant difference in CD68, BCL2 (p < 0.05 in both), and CD31 (p < 0.001) expression with CC. The internalized cells showed positivity for CD68 and negativity for BCL2. Regression analysis revealed that tumor grade, CD31 and BCL2 immunoreactivity were significant predictors of frequency of CC. The association of CC with degree of differentiation, CD31, CD68, and BCL2 expression could predict the biological behavior of OSCC and might serve as a promising histopathological parameter in future.

Uterine smooth muscle tumors of uncertain malignant potential: a retrospective evaluation of clinical pathology and immunohistochemistry features

BackgroundUterine smooth muscle tumor of uncertain malignant potential (STUMP) is a group of uterine smooth muscle tumors which cannot be classified as a subtype of leiomyoma or leiomyosarcoma. Diagnosis, prognosis, and treatment of these tumors are challenging due to recurrence, potential of malignancy, and metastasis.MethodsA retrospective cohort study was conducted in southern Iran during 2011 to 2020. We included records of 21 patients with STUMP and 24 patients with leiomyoma by simple randomized sampling in the tertiary health care centers in Shiraz, southern Iran. Slides were reviewed by an expert pathologist for examining mitosis, necrosis, and atypia, and also proper blocks were selected for immunohistochemistry (IHC) staining.ResultsFrom 45 participants, 21 (46.7%) and 24 (53.3%) patients were in the STUMP and normal leiomyoma groups, respectively. Odds ratio and 95% confidence interval (OR (95% C.I)) of pathologic size in the range of 5–10 cm was significantly higher in the STUMP group compared with normal leiomyoma. (CI: 7.22 (1.44–36.22)). Additionally, hyaline necrosis 0.05 (0.0-0.91), mild to moderate atypia 0.02 (0.0-0.4), moderate to severe atypia 0.01 (0.0-0.22), focal atypia 0.01 (0-0.26) and diffuse atypia 0.01 (0-0.26) were significantly fewer in normal leiomyoma compared to the STUMP group. Negative P16 0.01 (0.0007-0.24) and negative Bcl2 0.22 (0.06–0.81) were significantly higher in the normal leiomyoma group compared with the STUMP group. The cut-off points for predicting STUMP were 2.5% (sensitivity = 62% and specificity = 100%) and 45% (sensitivity = 43% and specificity = 96%) for P16 and bcl2, respectively.ConclusionThe category and management of STUMP continues to progress. The diagnosis for STUMP mainly depends on the histopathological manifestations. No single IHC marker such as P53, P16, and Bcl-2 has proved robust enough in separating STUMP from other leiomyoma variants; however, according to our study, we suggest combination use of P16 and Bcl-2 (cut off 2.5 and 45%, respectively) to distinguish equivocal cases of STUMP.

Advanced Pediatric-Type Follicular Lymphoma, Consequences of a Late Presentation in a Resource-Poor Setting: Case Report and Literature Review

AbstractPediatric-type follicular lymphoma (PFL) is a rare, nonaggressive, slow-growing (indolent), non-Hodgkin lymphoma that is typically seen in males as a localized disease with excellent outcomes. It is largely different from follicular lymphoma (FL). Few published studies on PFL are case series in developed nations. We report on a patient with advanced PFL, a 14-year-old female with 5-year history of neck swellings, abdominal distension for a month, and pericardial effusion, among others. The swellings waxed and waned; and involved all the peripheral lymph nodes. Tuberculosis (TB) GeneXpert and human immunodeficiency virus (HIV) screening were negative. She received anti-TB drugs prior to presentation in our hospital where nodal histopathology showed effaced architecture with diffuse follicles and abundant blastoid cells as well as negative CD5 and BCL2, and positive CD10 and CD20. Diagnosis of PFL (stage 3) was made. She completed six courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone and is well 9 months after therapy. The PFL usually presents with stage 1 or 2 disease unlike in the index female case that was also complicated by effusion and ascites due to late presentation. It responded to chemotherapy and has not reoccurred; in contrast to classic FL and reactive follicular hyperplasia (RFH) which should be differentiated from PFL. Although RFH can be caused by TB or HIV, they are not causes of malignant lymphadenopathy. Physicians should be aware of PFL which may present in high clinical stages, but still retain its good prognosis, for the purposes of counseling.

Nintedanib reduces corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice by increasing the expression of β3 and β6 integrins

Background: Pulmonary fibrosis is a progressive lung disorder that occurs by lung injury and scarring of the lung tissue. This injury makes the lung thickened and stiff causing difficulty to breathe. Corticosteroid resistance pulmonary fibrosis is a major health problem. Bleomycin is an anti-cancer agent, it induces pulmonary fibrosis resistance to corticosteroid therapy, this study aimed to determine the effectiveness of nintedanib (NIN) a tyrosine kinase inhibitor on corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice. Methods: Sixty albino male adult mice were used in this study. The mice were divided into five groups (n=12) at random. control group, the BLM group received a single dose of bleomycin (BLM); 2U/kg by endotracheal instillation, the BLM+MP group received bleomycin and methylprednisolone (MP) 10mg/kg/day by gastric gavage, BLM+NIN group received BLM and NIN, 60mg/kg/day by gastric gavage and the combined treatment group received BLM, NIN, and MP. All groups were sacrificed after the last dose of treatment on day 7 (acute stage) and day 28 (chronic stage). The lung tissues were obtained for biochemical analysis, gene expression, and histopathological examination at the end of the experiment. Results: After 7 days of treatments, BLM+NIN and BLM + NIN + MP groups showed a significant (P&lt;0.05) decrease in the contents of interleukin-2, interleukin-4, interferon-gamma, tumor necrosis factor-alpha, Malondialdehyde with an increase in the glutathione content in lung tissue compared to MP group. Also, they showed a significant decrease in the lung water content compared to the BLM group treated with MP. After 28 days, both NIN groups showed a significant reduction in hydroxyproline, and transforming growth factor beta (β) contents in the lung tissues compared to the MP group, and they showed a positive effect on the expression of β3 and β6 integrins compared to the negative effect of the MP group. Upon histopathology examination, the BLM+NIN group and BLM + NIN + MP groups showed significant improvement compared to the MP group by hematoxylin and eosin (H and E) and Masson’s trichrome stains. Immunohistochemical staining revealed negative BCL-2 expression in the cytoplasm of bronchiolar epithelium in BLM+NIN and BLM + NIN + MP groups after 7 and 28 days of treatment. Morphometric studies of lung tissue showed significant improvement in pathological changes induced by BLM in the BLM+NIN group and BLM + NIN + MP groups. Conclusion: Altogether, our data indicate that NIN overcame corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice mainly by decreasing TGF-β and improving the expression of β3 and β6 integrins.

Hypoxia-induced autophagy in triple negative breast cancer: association with prognostic variables, patients’ survival and response to neoadjuvant chemotherapy

Autophagy is a cellular response to diverse stresses within tumor microenvironment (TME) such as hypoxia. It enhances cell survival and triggers resistance to therapy. This study investigated the prognostic importance of HIF-1α and miR-210 in triple negative breast cancer (TNBC). Also, we studied the relation between beclin-1 and Bcl-2 and their prognostic relevance in triple negative breast cancer. Furthermore, the involvement of hypoxia-related markers, beclin-1 and Bcl-2 in mediating resistance to neoadjuvant chemotherapy (NACT) in TNBC was evaluated. Immunohistochemistry was performed to evaluate HIF-1α, beclin-1 and Bcl-2 expression whereas, miR-210 mRNA was detected by quantitative reverse transcription PCR (q-PCR) in 60 TNBC patients. High HIF-1α expression was related to larger tumors, grade III cases, positive lymphovascular invasion, advanced stage, high Ki-67 and poor overall survival (OS). High miR-210 and negative Bcl-2 expression were related to nodal metastasis, advanced stage and poor OS. High beclin-1 was associated with grade III, nodal metastasis, advanced stage and poor OS. Also, high beclin-1 and negative Bcl-2 were significantly associated with high HIF-1α and high miR-210. High HIF- 1α, miR-210 and beclin-1 as well as negative Bcl-2 were inversely related to pathologic complete response following NACT. High beclin-1 and lack of Bcl-2 are significantly related to hypoxic TME in TNBC. High HIF-1α, miR-210, and beclin-1 expression together with lack of Bcl-2 are significantly associated with poor prognosis as well as poor response to NACT. HIF-1α and miR-210 could accurately predict response to NACT in TNBC.

Prognostic value of combining E-cadherin, p53, Bcl-2 and Bcl-xL expression and survival in Tunisian colorectal adenocarcinoma patients.

Colorectal cancer (CRC) is a commonhealth issue worldwide with an extremely low survival rate after relapse. This study aims to evaluate the immunohistochemical expression of p53, E-cadherin, Bcl-2 and Bcl-xL and find a potential correlation between these markers, clinicopathological factors and overall survival of colorectal cancer patients. Marker expression was immunohistochemically determined in 105 patients with colorectal adenocarcinoma from southern Tunisia, followed by statistical analysis. Positivity rate of nuclear p53, membranous E-cadherin and cytoplasmic Bcl-2 - Bcl-xL was 85.71%, 76.47%, 59.8%, and 85.71% respectively. Spearman correlation showed that p53 was significantly and positively related to E-cadherin, Bcl-2, Bcl-xL and distant metastasis. A positive significant correlation between E-cadherin and anti-apoptotic proteins was also seen. Membranous E-cadherin expression was significantly and negatively associated to poor prognosis factors including lymph node metastasis, lymph invasion, venous invasion and distant metastasis. Bcl-2 expression was significantly correlated to distant metastasis. Multivariate analysis showed a significant association between dependent variable E-cadherin and covariates including differentiation, lymph invasion, venous invasion, distant metastasis, Bcl-2 and Bcl-xL. Poor 3-years OS and 5-years OS were significantly related to p53, Bcl-2 expression and E-cadherin loss. Positive E-cadherin combined with negative p53 and Bcl-2 as well as double-positive for E-cadherin and Bcl-xL were associated to best overall survival. Although each protein can be an independent prognostic factor, Simultaneous E-cadherin, p53, Bcl-2, Bcl-xL expression could be a crucial prognostic and overall survival marker to CRC patients. Multivariate analysis confirmed a positive correlation between membranous E-cadherin loss and colorectal cancer severity.

Lymphoid hyperplasia with a polyp form of the gallbladder macroscopically mimicking carcinoma

Lymphoid hyperplasia is a type of tumor-like hyperplasia of lymphoid tissue. There have been few reports on lymphoid hyperplasia of the gallbladder. Here, we report a case of lymphoid hyperplasia with a polyp form of the gallbladder macroscopically mimicking carcinoma. Liver dysfunction was diagnosed in a 75-year-old woman who presented with a gallbladder mass measuring 20mm during an annual health checkup. Antibody tests for infectious diseases were positive for anti-HBs and anti-HBc antibodies. Accordingly, a laparoscopic cholecystectomy was performed. Macroscopically, the mass was a papillary/sessile tumor (29 × 25mm) located in the fundus of the gallbladder. Histologically, the tumor was accompanied by an erosion on a portion of the surface layer, while the remaining epithelium showed regenerative changes and mild hyperplasia. No atypia was observed in the constituent epithelium. Hyperplasia of the polarized lymphoid follicles was observed in the interstitium, and tingible body macrophages were scattered in the germinal center. Immuno-histologically, the germinal center showed CD20 positivity, weak CD10 positivity, Bcl-2 negativity, and a high Ki-67 index (MIB-1). These findings suggested that the proliferating lymphoid follicles were reactive rather than neoplastic. Therefore, we diagnosed the patient with lymphoid hyperplasia of the gallbladder and chronic cholecystitis.

Expression of Friend Leukemia Integration-1 (Fli-1) and the Apoptosis Regulator B Cell Lymphoma-2 (BCL-2) in Gastric Carcinoma; an Immunohistochemical Study

ABSTRACT Fli-1 regulates multiple biological functions in different cancers particularly Ewing sarcoma and leukemias. There are controversial reports regarding function and prognostic significance of Fli-1 in epithelial cancer including gastric carcinoma (GC). No previous reports examined relationship between Fli-1 and BCL-2 in GC. This study aimed to investigate the expression of Fli-1 and BCL-2 in GC and expected the prognostic significance of their expression. Study was carried out on 88 gastric specimens (58 GC and 30 chronic gastritis cases). Immunohistochemical staining for Fli-1 and BCL-2 was done. There was significant lower Fli-1 and BCL-2 expression in GC than chronic gastritis. Advanced tumor stage showed significant relation with both low Fli-1 expression and negative BCL-2 expression. There was significant direct correlation between BCL-2 positivity and Fli-1 expression in GC. Cox-regression analysis showed that distant metastasis was the first independent factor affecting patients’ OS. Fli-1 could act as tumor-suppressor protein involved in GC carcinogenesis. In addition, both Fli-1 and BCL-2 may be used as good prognostic markers in GC. The direct correlation between BCL-2 and Fli-1 expression could potentiate Fli-1 and BCL-2 as therapeutic targets in GC, acting together to inhibit cellular proliferation.

RBM10 Regulates Tumor Apoptosis, Proliferation, and Metastasis.

The RNA-binding motif protein 10 (RBM10) is involved in alternative splicing and modifies mRNA post-transcriptionally. RBM10 is abnormally expressed in the lung, breast, and colorectal cancer, female genital tumors, osteosarcoma, and other malignant tumors. It can inhibit proliferation, promote apoptosis, and inhibit invasion and metastasis. RBM10 has long been considered a tumor suppressor because it promotes apoptosis through the regulation of the MDM2-p53 negative feedback loop, Bcl-2, Bax, and other apoptotic proteins and inhibits proliferation through the Notch signaling and rap1a/Akt/CREB pathways. However, it has been recently demonstrated that RBM10 can also promote cancer. Given these different views, it is necessary to summarize the research progress of RBM10 in various fields to reasonably analyze the underlying molecular mechanisms, and provide new ideas and directions for the clinical research of RBM10 in various cancer types. In this review, we provide a new perspective on the reasons for these opposing effects on cancer biology, molecular mechanisms, research progress, and clinical value of RBM10.

Methylation of the NT5E Gene Is Associated with Poor Prognostic Factors in Breast Cancer.

Cluster of differentiation (CD) 73, which is encoded by the NT5E gene, regulates production of immunosuppressive adenosine and is an emerging checkpoint in cancer immunotherapy. Despite the significance of CD73 in immuno-oncology, the roles of the NT5E gene methylation in breast cancer have not been well-defined yet. Therefore, we aimed to investigate the prognostic significance of the NT5E gene methylation in breast cancer. The DNA methylation status of the NT5E gene was analyzed using pyrosequencing in breast cancer tissues. In addition, the levels of inflammatory markers and lymphocyte infiltration were evaluated. The mean methylation level of the NT5E gene was significantly higher in breast cancer than in normal breast tissues. In the analysis of relevance with clinicopathologic characteristics, the mean methylation levels of the NT5E gene were significantly higher in patients with large tumor size, high histologic grade, negative estrogen receptor expression, negative Bcl-2 expression, and premenopausal women. There was no difference in disease-free survival according to the methylation status of the NT5E gene. We found that the NT5E gene methylation was related to breast cancer development and associated with poor prognostic factors in breast cancer. Our results suggest that the NT5E gene methylation has potential as an epigenetic biomarker in breast cancer.

A Diagnostic Approach to the Identification of Burkitt-like Lymphoma With 11q Aberration in Aggressive B-Cell Lymphomas.

Rare cases of aggressive B-cell lymphomas with a morphology similar to Burkitt lymphoma (BL) present with the BL-typical immunophenotype, but lacked MYC translocation (MYC-negative Burkitt-like lymphoma: mnBLL). A proportion of those with an imbalance pattern in chromosome 11q has been designated Burkitt-like lymphoma with 11q aberration in the recent update of the World Health Organization (WHO) classification. Because of the problems in the identification of Burkitt-like lymphoma with 11q aberration, our goal was to retrospectively analyze their frequency in a cohort of "candidate" aggressive lymphomas (cohort 1, n=35) such as mnBLL (n=16), diffuse large B-cell lymphoma with similarities to Burkitt lymphoma (DLBCL-BL; n=3), high-grade B-cell lymphomas, not otherwise specified (NOS) (n=16), as well as in a cohort of MYC-negative diffuse large B-cell lymphoma NOS (cohort 2, n=62). In total, 17/33 cohort 1 cases (52%) harbored the typical 11q aberration pattern, predominantly those that had been classified as mnBLL (12/16, 75%), but also as DLBCL-BL (2/3, 67%) and high-grade B-cell lymphomas, NOS (3/14; 21%). The specimens with this typical 11q aberration pattern were usually negative for the BCL2 protein. Of interest and as a new finding, samples harboring the 11q aberration pattern were often characterized by strikingly coarse apoptotic debris within starry sky macrophages facilitating their recognition. In contrast, only 1 of 62 garden variety DLBCL, NOS was positive for the 11q aberration pattern. In 2 DLBCL-BL, a dual MYC translocation/11q aberration pattern was detected. As a diagnostic algorithm, we, therefore, propose analysis of 11q status in MYC-negative high-grade lymphomas with features of BL, especially showing BCL2 negativity and a conspicuous coarse apoptotic debris in starry sky macrophages.

Differential expression and prognostic relevance of autophagy-related markers ATG4B, GABARAP, and LC3B in breast cancer.

Previous studies indicate that breast cancer molecular subtypes differ with respect to their dependency on autophagy, but our knowledge of the differential expression and prognostic significance of autophagy-related biomarkers in breast cancer is limited. Immunohistochemistry (IHC) was performed on tissue microarrays from a large population of 3992 breast cancer patients divided into training and validation cohorts. Consensus staining scores were used to evaluate the expression levels of autophagy proteins LC3B, ATG4B, and GABARAP and determine the associations with clinicopathological variables and molecular biomarkers. Survival analyses were performed using the Kaplan-Meier function and Cox proportional hazards regression models. We found subtype-specific expression differences for ATG4B, with its expression lowest in basal-like breast cancer and highest in Luminal A, but there were no significant associations with patient prognosis. LC3B and GABARAP levels were highest in basal-like breast cancers, and high levels were associated with worse outcomes across all subtypes (DSS; GABARAP: HR 1.43, LC3B puncta: HR 1.43). High ATG4B levels were associated with ER, PR, and BCL2 positivity, while high LC3B and GABARAP levels were associated with ER, PR, and BCL2 negativity, as well as EGFR, HER2, HER3, CA-IX, PD-L1 positivity, and high Ki67 index (p < 0.05 for all associations). Exploratory multi-marker analysis indicated that the combination of ATG4B and GABARAP with LC3B could be useful for further stratifying patient outcomes. ATG4B levels varied across breast cancer subtypes but did not show prognostic significance. High LC3B expression and high GABARAP expression were both associated with poor prognosis and with clinicopathological characteristics of aggressive disease phenotypes in all breast cancer subtypes.

PD-L1 and miR-34a are Prognostic Factors for Primary Gastric Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP.

IntroductionPrimary gastric diffuse large B-cell lymphoma (GDLBCL) is a heterogeneous disease in clinicopathological features and prognosis. Programmed death ligand-1 (PD-L1) and microRNA-34a (miR-34a) play crucial roles in GDLBCL progress. The purpose of this research is to explore the clinical significance of PD-L1 and miR-34a expression in GDLBCL.Patients and MethodsThe expressions of PD-L1 and miR-34a were examined by IHC and qRT-PCR in 109 patients who were diagnosed with GDLBCL and were treated with rituximab plus cyclophosphamide, doxorubicin, prednisone vincristine and prednisone chemotherapy (R-CHOP) from January 2010 to December 2018.ResultsPD-L1 level was significantly higher in tumor tissues than adjacent non-tumor tissues (60.5%, P<0.001), while the miR-34a level was just reversed (50.5%, P<0.001), which was negatively correlated (r=−0.524, P<0.001). Notably, PD-L1-positive and miR-34a-negative expressions were significantly correlated with the advanced Lugano stage of IIE-IV stage (P<0.001 and P<0.01), elevated serumal LDH levels (P<0.001 and P<0.05), B symptoms present (P<0.001 and P<0.001), non-GCB subtype (P<0.001 and P<0.001) and negative Bcl-2 expression (P<0.05 and P<0.001). PD-L1 high and miR-34a low expression groups had more patients with IPI scores of 2 or greater (P<0.001 and P<0.05) and poor R-IPI (P<0.01 and P<0.01). The complete response rate was upregulated in patients with negative PD-L1 and positive miR-34a expression after R-CHOP treatment.DiscussionPD-L1 expression and miR-34a expression were significantly associated with clinicopathological characteristics and survival prognosis; they may serve as novel prognostic markers in GDLBCL patients who were treated with R-CHOP. Immunotherapies targeting PD-L1 and miR-34a pathway may have therapeutic potential in GDLBCL.

The tripartite interaction of phosphate, autophagy, and αKlotho in health maintenance.

Aging-related organ degeneration is driven by multiple factors including the cell maintenance mechanisms of autophagy, the cytoprotective protein αKlotho, and the lesser known effects of excess phosphate (Pi), or phosphotoxicity. To examine the interplay between Pi, autophagy, and αKlotho, we used the BK/BK mouse (homozygous for mutant Becn1F121A ) with increased autophagic flux, and αKlotho-hypomorphic mouse (kl/kl) with impaired urinary Pi excretion, low autophagy, and premature organ dysfunction. BK/BK mice live longer than WT littermates, and have heightened phosphaturia from downregulation of two key NaPi cotransporters in the kidney. The multi-organ failure in kl/kl mice was rescued in the double-mutant BK/BK;kl/kl mice exhibiting lower plasma Pi, improved weight gain, restored plasma and renal αKlotho levels, decreased pathology of multiple organs, and improved fertility compared to kl/kl mice. The beneficial effects of heightened autophagy from Becn1F121A was abolished by chronic high-Pi diet which also shortened life span in the BK/BK;kl/kl mice. Pi promoted beclin 1 binding to its negative regulator BCL2, which impairs autophagy flux. Pi downregulated αKlotho, which also independently impaired autophagy. In conclusion, Pi, αKlotho, and autophagy interact intricately to affect each other. Both autophagy and αKlotho antagonizes phosphotoxicity. In concert, this tripartite system jointly determines longevity and life span.

Combined p53 and Bcl2 Immunophenotypes in Prognosis of Vietnamese Invasive Breast Carcinoma: A Single Institutional Retrospective Analysis

Background:Aberrant of p53 and Bcl2 genes cause changes in the quantity and quality of their proteins and contribute to the pathogenesis of some cancer types including breast cancer. Expression of p53 and Bcl2 were associated to adverse clinical outcomes in breast cancer.Purpose:To predict the survival outcomes of invasive breast cancer in Vietnam, using immunohistochemical expression of p53, Bcl2 proteins.Methods:The current study was conducted on 526 breast cancer patients who had surgical operations, but had not received neo-adjuvant chemotherapy, from 2011 to 2014. The clinicopathological characteristics were recorded. Immunohistochemical staining was performed on p53, Bcl2 markers. Expression of p53 and Bcl2 were paired into different immunophenotypes for analysis with clinicopathological characteristics and survival. All breast cancer patients’ survival were analyzed by using Kaplan-Meier and Log-Rank models.Results:The presence of p53 protein was detected in 44.1%. Positive p53, and p53+Bcl2- immunophenotype were significantly associated with poorer prognostic features. In contrast, the positive Bcl2 protein accounted on 57.6%, and combination of p53-Bcl2+ were strong correlated with better clinicopathological parameters. Bcl2 positivity was observed in higher than the negative Bcl2 in the five-year OS (Overall survival) proportion (91.2 vs 79.4%, respectively) (p < 0.05). Multivariate analysis revealed that the expression of p53, Bcl2 or combinations of these 2 proteins was no longer remained as an independent prognostic variable.Conclusion:The Bcl2 positivity had a distinct OS and DFS (Disease free survival). The expression of p53 and Bcl2 are inversely correlated to clinical outcomes in breast cancer.

Prognostic Significance of BCL2 Protein in Diffuse Large Cell Lymphoma of Head and Neck; Relation to Response to Chemotherapy

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that displays a highly variable clinical outcome. It is a neoplasm of large transformed B cells with a diffuse growth pattern. DLBCL is the most common type of non-Hodgkin’s lymphoma (NHL) (31% of all cases). Approximately half of patients with DLBCL are cured with current chemotherapy regimens. The purpose of this study was to evaluate BCl2 expression in 45 patients diagnosed with DLBCL of head and neck region and correlate the level of its immunohistochemical expression with different clinicopathological variables with emphasis upon patients’ age, gender, nodal or extra-nodal location of lymphoma, patients’ response to chemotherapy, progression-free survival (PFS) and overall survival (OS). A retrospective analysis of 45 patients diagnosed to have DLBCL. A cut off value of ≥ 50% protein expression denoted BCL2 positivity. Out of 45 cases, 36 cases (80%) revealed BCL2 positive expression and 9 cases (20%) were BCL2 negative. We found statistically significant differences in BCL2 expression regarding different patients’ responses to chemotherapy, patients’ OS and PFS (p ≤ 0.05). No statistically significant differences in BCL2 expression regarding the patients’ Ann Arbor clinical stage, age group and tumor site (nodal or extra-nodal, p > 0.05) using the Chi-square test. BCL2 expression was analyzed in relation to 5 years OS and PFS using Kaplan Meier curves and Log Rank test for survival analysis. Cases that demonstrated BCL2 positivity revealed shortened OS and PFS with highly statistically significant differences among the studied variables (p = 0.000). We also found that patients who respond well to the chemotherapeutic regimen had negative BCL2 expression, the differences were statistically significant (p = 0.015). In conclusion, BCL2 expression could be considered a predictor for patients’ chemotherapeutic response, OS and PFS.

CLINICOPATHOLOGIC AND IMMUNOHISTOCHEMICAL FEATURES OF 2 CASES OF SOLITARY FIBROUS TUMOR OF THE ORAL CAVITY

Solitary fibrous tumor (SFT) is an uncommon soft tissue tumor that usually occurs in the pleura, but it is extremely rarely in the oral cavity. It presents an extensive microscopic diversity that may turn the diagnosis into a challenge. This is the report of 2 new cases of SFT in the buccal mucosa and tongue highlighting the clinical, microscopic, and immunohistochemical variations. The study included 2 women at 49 and 80 years old. Clinically, they were slow-growing, painless, small, well-defined submucosal masses. Microscopic examination showed well-circumscribed spindle cell proliferations associated with alternating dense hyalinization areas and characteristic stag horn-shaped blood vessels in variable arrangements. Immunohistochemistry showed consistently positivity for CD34 and vimentin, alternating positivity for Bcl-2 and epithelial membrane antigen and negativity for S-100. Patients are well with no recurrence or relapse.

Neuroprotective effects of allopurinol on spinal cord injury in rats: a biochemical and immunohistochemical study.

Lesion in spinal cord causes a cascade of events such as the apoptosis of neurons and eventually, neurological dysfunction. Neurologic damage developing after acute spinal cord injury is also related with necrosis and free radical formation. Allopurinol, a xanthine oxidase inhibitor, was shown to have protective effects in several studies. B-cell lymphoma 2 (Bcl-2) family proteins regulate apoptosis. Apoptosis causes the death of neuronal cells, particularly neurons and oligodendrocytes in the spinal cord after lesion. Glial fibrillary acidic protein (GFAP) takes part in astrocyte and neuronal interconnection and synaptic transmission. Male Sprague Dawley rats (n = 30) were divided as control, trauma, and trauma + allopurinol (i.p., 50 mg/kg of body weight) groups. Animals were applied a surgical procedure causing spinal cord injury and treated for 7 days then sacrificed under anaesthesia. The spinal cords were dissected, measurements of myeloperoxidase, malondialdehyde and glutathione were performed, remaining parts were fixed in 10% formaldehyde solution for histological and immunohistochemical evaluations. Biochemical results exhibited an increase in myeloperoxidase levels in trauma group but a decrease in the allopurinol treatment group similar to malondialdehyde levels. Degenerative changes in multipolar and bipolar neurons together with apoptotic changes in some glial cells were observed in the trauma group whereas, mild degenerative changes were observed after allopurinol treatment. In the trauma group, negative GFAP expression in multipolar versus bipolar neuronal processes with a reduction in glial processes around blood vessels and positive GFAP expression were observed but, a regular and parallel positive GFAP expression of glial processes around blood vessels in the allopurinol treated group was apparent. Trauma group depicted a positive Bcl-2 expression in glial cells and in motor and bipolar neurons. On the contrary, negative Bcl-2 expression was noticed in the trauma + allopurinol group. This study is of importance to understand the effects of allopurinol in preventing degenerative changes in nerve and glial cells related to spinal cord injuries.

T(11;14) and High BCL2 Expression Are Predictive Biomarkers of Response to Venetoclax in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Biomarker Analyses from the Phase 3 Bellini Study

T(11;14) and High BCL2 Expression Are Predictive Biomarkers of Response to Venetoclax in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Biomarker Analyses from the Phase 3 Bellini Study

413P - The state of molecular biological markers in osteosarcoma

BackgroundTo study of immunohistochemical markers of proliferation and apoptosis are important prognostic indicators for predicting the clinical course of tumours and the development of therapeutic tactics. MethodsThe p53 suppressor gene, the bcl-2 oncogene and the Ki-67 antigen are responsible for DNA repair, cell division and apoptosis. In all patients, tumour material was obtained using biopsies and operations. In tumour tissue samples fixed by neutral formalin with standard wiring and embedded in paraffin, tumour markers of apoptosis and proliferation were determined - p53, bcl-2, Ki – 67. A positive result was the presence of specific brown staining of the nuclei in the detection of the Ki-67 antigen and the p53 gene suppressor and the cytoplasm in the detection of the expression of bCl-2. ResultsCases where the nucleus or cytoplasm was not stained by reaction with antibodies to p53, Ki-67 and bcl-2 or the number of positive cells was less than 10%, the reaction was considered negative (0). Weak (1+) reaction was considered when staining 10-30% of cells; medium reaction (2+) - when staining 30-50% of cells; strong reaction (3+) - intense staining from 70 or more cells. We carried out a comparative assessment of the effectiveness of treatment of patients depending on the type of therapy and the phenotype of tumour cells. Among patients who received systemic chemotherapy, the full effect was observed in 13% of patients. With negative and weakly positive reactions to the mutant p53 gene and Ki 67 among them was 70.6%, and with moderate and strong expression of bcl-2 (80%). Patients with a phenotype of tumour cells with a negative or weakly positive IHC response to the mutant p53 gene (58.5% of patients), weakly positive expression of Ki 67 (70.6% of patients), and high expression of bcl-2 (46.4 % of patients). In 37.4% of patients from this group, the effect of therapy was negative, most of them had tumour cells with high expression of the mutant p53 and Ki 67 gene, and no expression of bcl-2. ConclusionsIt was established that with positive expression of p53 + Ki-67 + and negative bcl-2 parameters, patients had an unfavourable prognosis. Legal entity responsible for the studyRonc. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.