Bcl-2 Positivity Research Articles

Biomarkers for Risk Stratification in Patients With Previously Untreated Follicular Lymphoma Receiving Anti-CD20-based Biological Therapy.

Follicular lymphoma (FL) is an indolent B-cell neoplasm of germinal center origin. Standard treatment regimens consist of anti-CD20 therapy with or without chemotherapy. While high response rates to initial therapy are common, patients ultimately relapse or have progressive disease. Clinical risk factors such as the Follicular Lymphoma International Prognostic Index (FLIPI) have been identified, but there is a need for prognostic and predictive biomarkers. We studied markers of lymphoma cells and tumor microenvironment by immunohistochemistry in tissue samples from patients enrolled in 1 of 4 phase 2 trials of anti-CD20-based biological therapy for previously untreated grades 1 to 2 or 3A FL. Results were correlated with progression-free survival (PFS) and PFS status at 24 months. The 4 trials included 238 patients (51.1% male, median age: 55 y) with stage III, IV, or bulky stage II disease. By FLIPI, 24.6% had low-risk, 56.8% had intermediate-risk, and 18.6% had high-risk disease. The outcome differed significantly for patients treated with lenalidomide and rituximab (CALGB 50803) compared with the other 3 trials (median: PFS not reached vs. 3.0 y, hazard ratio=3.47, 95% confidence interval: 2.11-5.72); therefore, data were stratified by clinical trial (CALGB 50803 vs. all others) and adjusted for FLIPI risk group. Among 154 patients with available tissue, interfollicular BCL6 positivity, interfollicular CD10 positivity, and elevated Ki67 proliferation index ≥30% within neoplastic follicles were each associated with inferior PFS and a high risk of the early event by PFS status at 24 months. We identify promising biomarkers for FL risk stratification that warrant further validation in phase 3 trials.

Immunoexpression of Apoptosis and Cell-cycle Arrest Markers in Oral Lichen Planus.

The expression pattern of a panel of 5 molecular markers (p53, cyclin D1, Ki-67, BCL-2, and BAX) was studied in samples from patients with oral lichen planus (OLP) and normal oral mucosa (NOM) of healthy controls to investigate the implications of cell cycle and apoptosis in OLP. The 59 OLP and 16 NOM biopsies were stained by an inmunoperoxidase technique for p53, cyclin D1, Ki-67, BCL-2, and BAX and assessed microscopically for semiquantitative analysis. Positivity for BCL-2 and Ki-67 was significantly more frequent in NOM than in OLP (P<0.05). p53 levels were upregulated in atrophic/erosive clinical presentations when compared with reticular presentations and in cases with discontinued inflammatory infiltrate. Multivariate analysis through logistic regression showed that BCL-2 in OLP versus NOM was the only significantly altered marker in the present cohort (adjusted odds ratio=12.42; 95% confidence interval: 2.5-61.65; P=0.002). The cell patterns in OLP and NOM are distinct according to the present molecular markers panel. The presence of BCL-2 altered expression may be related to various molecular pathways that connect/link this condition to other autoimmune disorders and also may be involved in complex roles that evoke malignant transformation of OLP.

LUNG AS THE PRIMARY SOURCE OF INTRAVASCULAR LARGE B CELL LYMPHOMA: A DIAGNOSTIC CHALLENGE

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Intravascular large B cell lymphoma (IVLBCL) is a rare form of Non-Hodgkin’s Lymphoma (NHL) that, in most cases, is disseminated at time of diagnosis with majority of manifestations in the central nervous system, cutaneous lesions, or hematologic syndromes. Lung involvement, though not uncommon, is most likely found during autopsy as early diagnosis of IVLBCL has proven to be difficult. CASE PRESENTATION: A 67 year-old male with no known medical history presented with progressive, subacute dyspnea and fatigue. On exam he was hypoxic with fine rales to auscultation and decreased air entry bibasally. Labs revealed moderate anemia, lactic acidosis, acute renal impairment, and transaminitis. CT chest non-contrast showed diffuse ground glass appearance with no acute consolidations or effusions. Peripheral blood smear showed no schistocytes; serum protein electrophoresis and erythrocyte sedimentation rate were unremarkable; ANCA and HIV were negative. Bone marrow biopsy was performed revealing hypercellularity with no evidence of malignancy; bronchoscopy was non-diagnostic. PET scan revealed areas of tracer uptake in the lungs and subsequent VATS with lung biopsy showed nonspecific pneumonitis: hilar membranes, reactive pneumocytes and collapsed vessels, making visualization of intravascular cell invasion difficult. Findings seemed consistent with interstitial lung disease, however, due to unknown origin of lung disease and acute onset of symptoms, the sample was sent for further pathologic review. Subsequent staining of cells revealed positive MUM-1, BCL-6 & BCL-2, CD45, CD20, PAX5, c-myc (20%) and Ki67. CD34 was negative. The final diagnosis was IVLBCL. DISCUSSION: IVLBCL is rare and characterized by the presence of tumor cells within blood vessels. The disease is highly malignant and carries a poor prognosis, as the majority of patients present late in disease course. The lung as a primary source of IVLBCL is a very rare occurrence with only a few cases reported. Although in this case diffuse ground glass appearance was present on chest CT, there was no explanation for pathology findings of interstitial lung disease, which necessitated further testing ultimately revealing a diagnosis. It is apparent that a confirmatory diagnosis of IVLBCL is quite difficult and involves intensive pathologic review. CONCLUSIONS: It is important for physicians to consider a diagnosis of IVLBCL, albeit rare, in patients who present with respiratory symptoms and no apparent cause. Ruling out other possible causes of clinical presentation, as well as adequate pathology samples, are paramount. Reference #1: 1.Yamashita, Hiroyuki, et al. “Intravascular Large B-Cell Lymphoma with Diffuse FDG Uptake in the Lung by 18FDG-PET/CT without Chest CT Findings.” Annals of Nuclear Medicine, vol 26, 27 Apr. 2012, pp. 515-521 Reference #2: 2.M. Fiegl, R. Greil, C. Pechlaner, J. Krugmann, S. Dirnhofer, Intravascular large B-cell lymphoma with a fulminant clinical course: a case report with definite diagnosis post mortem, Annals of Oncology, Volume 13, Issue 9, 2002 September, pp.1503–1506 Reference #3: 3.Ponzoni, Maurilio, et al. “Definition, Diagnosis, and Management of Intravascular Large B-Cell Lymphoma: Proposals and Perspectives From an International Consensus Meeting.” Journal of Clinical Oncology, vol 25, no. 21, 20 July 2007, pp. 3168-3173 DISCLOSURES: No relevant relationships by Lewis Attas, source=Admin input No relevant relationships by Alyssa Foster, source=Web Response No relevant relationships by Manuel Katz, source=Web Response No relevant relationships by Dan Ran-Castillo, source=Web Response No relevant relationships by Jonathan Shammash, source=Web Response No relevant relationships by Matthew Tavares, source=Web Response

ORAL SOLITARY FIBROUS TUMOR: MORPHOLOGIC AND IMMUNOHISTOCHEMICAL FINDINGS

Solitary fibrous tumor is an uncommon benign mesenchymal lesion. A 91-year-old male patient complained of an asymptomatic papule, reddish, pediculated, on the lateral border of the tongue, measuring 1.5 cm. An excisional biopsy was performed, and the diagnostic hypothesis of fibrous hyperplasia was considered. Microscopically, a circumscribed lesion was observed, with mesenchymal cells proliferation of variable morphology, with hypercellular and hypocellular areas. There was also ramifying vascular network, sometimes with a staghorn configuration, and the fibrous stroma exhibited focal areas of hyalinization. For the purposes of differential diagnosis, an immunohistochemical panel was performed. The positivity for vimentin, CD34, Bcl-2, and CD99, associated with lack of expression of S100, α–smooth muscle actin, CD68, and desmin led to the histopathologic diagnosis of solitary fibrous tumor. This case emphasizes the importance of immunohistochemical technique together with histopathologic features for the correct diagnosis of mesenchymal lesions.

SOLITARY FIBROUS TUMOR OF THE LOWER LIP: A CASE REPORT MIMETIZING MUCOCELE

A 58-year-old female patient presented complaints concerning a painless "bubble" in the lower lip with 7-month evolution, reporting episodes of remission and growth. In the medicine’s history there are no predisposing factors. The clinic examination revealed a normochromic bubble measuring 0.3 cm in vermillion of the lower lip region with a rubbery consistency. The clinical hypothesis of mucocele was established; thus, an excisional biopsy was performed. Histologic examination showed a benign neoplasm of mesenchymal origin with well-defined capsule characterized by proliferation of ovoid cells showing pale nuclei and spindle cells in a solid or papillary pattern from within fibrous connective tissue stroma. Immunohistochemical stains were performed and showed diffuse positivity for CD34 and α-smooth muscle actin and focal positivity for Bcl-2. Based on these findings the diagnosis of solitary fibrous tumor was established. No complementary treatment was performed. The patient was followed up for 6 months without recurrences. A 58-year-old female patient presented complaints concerning a painless "bubble" in the lower lip with 7-month evolution, reporting episodes of remission and growth. In the medicine’s history there are no predisposing factors. The clinic examination revealed a normochromic bubble measuring 0.3 cm in vermillion of the lower lip region with a rubbery consistency. The clinical hypothesis of mucocele was established; thus, an excisional biopsy was performed. Histologic examination showed a benign neoplasm of mesenchymal origin with well-defined capsule characterized by proliferation of ovoid cells showing pale nuclei and spindle cells in a solid or papillary pattern from within fibrous connective tissue stroma. Immunohistochemical stains were performed and showed diffuse positivity for CD34 and α-smooth muscle actin and focal positivity for Bcl-2. Based on these findings the diagnosis of solitary fibrous tumor was established. No complementary treatment was performed. The patient was followed up for 6 months without recurrences.

Date palm fruit extract ameliorated pancreatic apoptosis, endocrine dysfunction and regulatory inflammatory cytokines in Streptozotocin-induced diabetes in rats.

The current work studied the mechanism(s) and ability by which date palm (Phoenix dactylifera L.) fruit extract (DPE) inspired a glucose-lowering impact in rats suffering from diabetes. Forty-eight albino rats were divided into six various experimental treatments after induction of diabetes by intraperitoneal infusion of streptozotocin (45mg/kg bwt) as follows: normal control, DPE, diabetic control, diabetic glibenclamide (GLI), diabetic DPE, and diabetic GLI plus DPE-treated groups. In animals euthanized after 8weeks, blood and pancreatic tissue samples were assembled to assess different biochemical and histopathological changes. The expressions of insulin, B cell lymphoma-2 (Bcl-2), and cysteine aspartate-specific protease-3 (caspase-3) in islet β cells were also evaluated using immunohistochemical assessment. Diabetic rats exhibited hyperglycemia; increment of pancreatic malondialdehyde (lipid peroxidation biomarker), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); and decrement of plasma insulin and pancreatic antioxidants: glutathione, superoxide dismutase, and catalase values. Also, the pancreatic islets exhibited histopathological and morphometric alternations associated with weak positive insulin and Bcl-2 immunoreactivity and strong positive caspase-3 immunoreactivity. DPE and/or GLI, an anti-diabetic drug, improved the pancreatic histoarchitecture and improved β cell function and structure, which increased insulin levels and improved the insulin, Bcl-2, and caspase-3 immunoreactivity in diabetic rats. Nevertheless, the combined DPE and GLI therapy revealed a significant recovery and restoration of β cells' structure and function. The date palm fruit has anti-apoptotic, anti-inflammatory, and antioxidant activities and hypoglycemic effects, which in turn play a pivotal role in avoiding the progression of diabetes mellitus. Moreover, it could potentiate the glucose-lowering activity of anti-diabetic drugs.

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.

Primary monophasic synovial sarcoma of the cervical esophagus confirmed by detection of the SS18-SSX2 fusion transcripts: case report and literature review

BackgroundSynovial sarcoma (SS) of the esophagus is extremely rare. Because of the microscopic features of SS, the monophasic type can easily be misdiagnosed as other spindle cell tumors. Here, we present the first case of a primary SS of the esophagus in the presence of SS18-SSX2 fusion transcripts.Case presentationA 47-year-old Japanese woman was initially diagnosed with thyroid papillary carcinoma in the left lobe and leiomyoma of the cervical esophagus and subsequently underwent left thyroid lobectomy and enucleation of the esophageal tumor. Four years after the first surgery, the esophageal tumor recurred. Endoscopic biopsy of the tumor revealed atypical cell proliferation with spindle cell features and mitoses. Immunohistochemistry showed focal positivity for bcl-2 and HHF35. Furthermore, the presence of SS18-SSX2 fusion transcripts was confirmed by reverse transcription-polymerase chain reaction analysis, using a paraffin-embedded tumor specimen. Therefore, the tumor was diagnosed as monophasic SS of the cervical esophagus. We re-evaluated the surgical specimen enucleated 3 years previously, which was initially diagnosed as leiomyoma, and the diagnosis of SS was confirmed. The patient underwent cervical esophagectomy with isolated jejunal interposition reconstruction. Three years after the second surgery, SS recurred in the distal anastomotic site between the jejunum and the esophagus, and the patient underwent thoracoscopic esophagectomy with gastric conduit reconstruction. The pathological grade of the lesion worsened with every recurrence.ConclusionsMonophasic SS can be difficult to discriminate from other spindle cell tumors based on microscopy alone, and molecular analysis could be useful for confirming the precise diagnosis of monophasic SS.

Predicting transition from oral pre-malignancy to malignancy via Bcl-2 immuno-expression: Evidence and lacunae

Bcl-2 (B cell Lymphoma −2) family comprises of both anti-apoptotic and pro-apoptotic proteins whose altered expression or change in ratio inhibits apoptosis, and promotes tumor progression. The aim of this study is to assess the usefulness of Bcl-2 in distinguishing dysplastic or malignant epithelium from non-dysplastic or normal epithelium to aid in prediction of malignant transformation potential. Material and methodStudy group comprised of 30 cases of clinically diagnosed leukoplakia (OPMD), 15 cases of Oral Squamous Cell Carcinoma (OSCC) and 5 normal tissue samples. The labeling index of Bcl-2 was analyzed in immunohistochemically stained sections. Different statistical tools were used to analyze the data and to compare Bcl-2 expression qualitatively and quantitatively among all the groups. ResultsAn increasing trend of Bcl-2 immunoexpression was observed from normal epithelium to non-dysplastic and from non-dysplastic to dysplastic lesions. In OSCC, the peripheral cells in the differentiating epithelial islands (within the connective tissue) showed Bcl-2 immuno-reactivity, which gradually decreased towards the center. In contrast, intense and diffuse Bcl-2 immuno-reactivity was seen in poorly differentiated carcinoma. But the overall Bcl-2 positivity was less in OSCC as compared to dysplastic lesions. ConclusionIncreased expression of Bcl-2 oncoprotein in sequentially progressing epithelial dysplasia and down-regulation in differentiating carcinoma (well and moderately differentiating OSCC) unveils the clinical relevance of Bcl-2 in early stages of OSCC tumorigenesis. The heterogenous expression of Bcl-2 in carcinoma with different grades of differentiation renders them unable to be used as an independent tool for predicting transition from oral pre-malignancy to malignancy.

Quantitative analysis of tumor-specific BCL2 expression in DLBCL: refinement of prognostic relevance of BCL2

BCL2 overexpression has been reported to be associated with poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL). However, currently there is no consensus on the evaluation of BCL2 expression and only the proportion of BCL2 positive cells are evaluated for the determination of BCL2 positivity. This study aimed to define BCL2 positivity by quantitative analysis integrating both the intensity and proportion of BCL2 expression. BCL2 expression of 332 patients (221 patients for the training set and 111 patients for the validation set) with newly diagnosed DLBCL who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) were analyzed using the tumor-specific automated quantitative analysis (AQUA) scoring method based on multiplex immunofluorescence. In the training set, high BCL2 AQUA score (N = 86, 38.9%) was significantly associated with poor prognosis (p = 0.01, HR 2.00; 95% CI [1.15–3.49]) independent of international prognostic index, cell of origin, and MYC expression. The poor prognostic impact of the high BCL2 AQUA score was validated in the validation set. AQUA scoring of BCL2 expression incorporating both the intensity and proportion of BCL2 positive cells was independently associated with survival outcomes of patients with primary DLBCL treated with R-CHOP.

SAT-202 Hypoglycemia Following Unilateral Pheochromocytoma Resection in the Immediate Post-Surgical Period

IntroductionHypoglycemia in the immediate post-resection period of unilateral pheochromocytoma is a potential complication but not very well recognized.Clinical CaseA 47 year old female with past medical history of Hypertension, coronary artery disease, Myocardial infarction, Depression, Systemic lupus erythematosus presented to the hospital initially for elective robotic assisted Left adrenalectomy. CT scan showed a big left adrenal mass with normal right adrenal gland. It was clinically diagnosed as Pheochromocytoma as outpatient by primary internist. Biochemical studies showed elevated serum metanephrines and normetanephrines, and urine normetanephrine.Post-surgery (< 24 hours) patient had episodes of fasting hypoglycemia with blood glucose levels as low as 68 mg/dl, accompanied with neuroglycopenic symptoms like tremors, sweating and palpitations.High dose ACTH stimulation test was performed. Serum cortisol levels were tested as 5.1, 11.7 and 14.4 mcg/dl within 0, 30 minutes and 60 minutes of Cosyntropin 250 mcg IV injection.The patient was started on Prednisone 5 mg daily to prevent any further episodes, which was successful, and was stopped by the patient one week after discharge, without any more hypoglycemia episodes. Further endocrinology work up could not be done as the patient did not follow up.Post-surgical pathology showed a 7x 5.5 x4 cm mass, which was confirmed as pheochromocytoma histopathologically and immunohistochemically by positive chromogranin, synaptophysin and BCl2 and negative for calretinin and S100.Discussion and ConclusionThe etiology of hypoglycemia after resection of unilateral pheochromocytoma can be explained by impaired glucagon secretion and decreased gluconeogenesis due to the suppression from higher catecholamine levels in the blood pre-operatively. The second mechanism is rebound insulin secretion from the pancreas due to sudden withdrawal of catecholamines.In our patient, the transient hypocortisolemia could be another reason. The lack of immunohistochemical evidence in post-surgical pathology report excluded cortisol- secreting tumor. Another rare situation, ACTH-secreting pheochromocytoma, has been reported but was not checked in the case.In a word, hypoglycemia is common after surgical removal of unilateral pheochromocytoma. Careful monitoring of patients’ glucose level in immediate post-resection period is essential to prevent transient hypoglycemia

Clinical, histopathologic, subtype, and immunohistochemical analysis of jaw phosphaturic mesenchymal tumors.

Jaw phosphaturic mesenchymal tumors (PMTs) are a rare neoplasm with uncertain histogenesis. This study aimed to clarify the clinical and pathological features of jaw PMTs.We reviewed the clinical records of 39 patients diagnosed with PMTs in the jaws, and investigated clinical and morphologic characteristics, histologic subtypes, and immunophenotypes of all cases.Microscopic analyses revealed 2 major histologic tumor subtypes: “phosphaturic mesenchymal tumors of mixed epithelial and connective tissue” (PMTMECT), and “phosphaturic mesenchymal tumors of mixed connective tissue” (PMTMCT). PMTMECTs and PMTMCTs accounted for 29 and 10 cases of PMTs, respectively. Most PMTMECT diagnoses were made predominantly in males aged <45 years, and the incidence was similar in both the mandible and maxilla. In contrast, patients with PMTMCTs are predominantly females aged ≥45 years, and all tumors were in the mandible. Histologically, PMTMECT had lower cellularity and a more elongated and spindled mesenchymal component with less elaborate intrinsic microvasculature than PMTMCT. Immunohistochemically, the epithelia of all PMTMECTs was immunoreactive for AE1/AE3. Other immunohistochemical staining of PMTMECTs revealed positive expression of vimentin, SATB2, ERG, CD99, Bcl-2, CD56, S-100, D2-40, CD68, SMA, and CD34 in either one or both components. Immunohistochemical staining of PMTMCTs was diffusely positive for vimentin and a varied ratio of positivity for SATB2, ERG, CD99, Bcl-2, CD56, S-100, D2-40, CD68, SMA, and CD34, but negative for AE1/AE3. Most patients were cured by complete resection, except 2 patients who had repeated recurrences, one of which also had multiple metastasis.Jaw PMT can be divided into 2 major histological subtypes. PMTMECTs are more common than are PMTMCTs, and can transform into malignant PMTMCTs during the progression. PMTMECTs were more commonly observed in males and the incidence was similar in both the maxilla and mandible. PMTMCTs were almost always observed in the mandible of females. Compared with PMTMCTs, PMTMECTs have an admixture of epithelial components with less prominent vasculature and lower cellularity. There were no statistically significant differences in the expression of immunohistochemical markers except AE1/AE3 between PMTMECTs and PMTMCTs. However, immunohistochemical markers have great significance for differentiating other mesenchymal tumors.

GLI activated nested malignant epithelioid cell tumour

Soft tissue neoplasms displaying a nested epithelioid morphology and abnormalities of the GLI-1 locus are emerging as a distinctive new tumour type. In 2018, a series of 6 such tumours was published, showing frequent S100 positivity and a tendency for aggressive clinical behaviour. Recently, a case series was published describing a related group of tumours showing morphologic overlap with the earlier examples and harbouring GLI-1 amplification as an alternative pathway of GLI-1 activation. We report a 9-year-old female who presented with a 5-year history of a slowly growing lesion on the left great toe. Microscopy revealed a dermally-based tumour with a multinodular growth pattern, arranged in tight nests separated by thin fibrovascular septa. The tumour cells had uniform ovoid nuclei with granular chromatin and inconspicuous nucleoli. Necrosis was absent, but mitoses were frequent. There was strong positivity for BCL2, Glut A, and CD56. S100 was seen in isolated cells. FISH for GLI-1 and DDIT3 showed amplification of both loci. We propose the term ‘GLI-activated nested malignant epithelioid cell tumour’ to describe this entity. This case also highlights the utility of FISH for DDIT, which lies in close proximity to GLI on chromosome 7, as a surrogate marker for GLI-1 amplification.

Synergistic effects of bevacizumab in combination with β-elemene on subcutaneous xenografts derived from HCT-116 human colon cancer cells.

BackgroundTo observe the effect of bevacizumab in combination with β-elemene on subcutaneous xenografts established from HCT-116 human colon cancer cells, explore the underlying mechanisms involved, and provide more options for the treatment of advanced colorectal cancer.MethodsMice were randomly divided into four groups: control, β-elemene, bevacizumab and combination treatment. Tumor volume was measured and the tumor inhibition rate and coefficient of drug interaction (CDI) were calculated. The pathological and morphological features of the tumor tissues were observed. Protein expression levels of ki-67, CD31, vascular endothelial growth factor (VEGF) and bcl-2 were measured by immunohistochemistry.ResultsThe tumor volumes in the four groups were 0.991±0.131, 0.833±0.145, 0.563±0.131 and 0.324±0.066 cm3, respectively. The tumor inhibition rates in the β-elemene, bevacizumab and combination groups were 15.9%, 43.2% and 67.3%, respectively. The degree of tumor reduction in the combination group was the most significant (P<0.05), with a CDI of 0.697. Immunohistochemistry showed that the ki-67 proliferation indexes in the four groups were 30.06%±3.37%, 19.79%±3.75%, 27.51%±2.16% and 16.9%±1.09%, the microvessel densities (MVDs) were 45.86±9.28, 31.14±5.58, 27.57±6.11 and 12.14±3.53, the rates of positive VEGF expression were 39.48%±6.72%, 28.86%±3.54%, 25.04%±2.64% and 19.5%±2.68%, and the rates of positive bcl-2 expression were 33.95%±6.38%, 20.11%±9.49%, 24.28%±6.57% and 11.18%±2.72%, respectively. Compared with the control group, the three experimental groups displayed different degrees of reduction in the above indicators (P<0.05), with the combination group exhibiting the lowest values (P<0.05).ConclusionsBevacizumab exerts a synergistic effect with β-elemene in suppressing the growth of tumors derived from HCT-116 cells, and the related mechanisms may include the inhibition of tumor cell proliferation and tumor angiogenesis and the promotion of tumor cell apoptosis.

The correlation between DNA mismatch repair status and the clinicopathological and molecular features of Chinese sporadic colorectal cancer

BackgroundDNA mismatch repair (MMR) genes play an important role in cancer development. Deficiencies in these genes may cause microsatellite instability (MSI), which can cause colorectal cancer (CRC). Therefore, we evaluate the relationship between MMR status and the clinicopathological and molecular features of Chinese patients with sporadic CRC.MethodsWe evaluated 1,405 patients who had undergone primary tumour resection, and divided them into MMR deficiency (dMMR) and MMR proficiency (pMMR) groups, according to their MMR gene expressions. All clinicopathological and molecular features were obtained from pathology reports.ResultsThe dMMR group contained 125 patients and the pMMR group contained 1 280 patients. Patients with dMMR were more likely to be younger (P<0.05), have poorly differentiated tumours (14.6%), tumours with negative peripheral nerve invasiveness (10.2%), and right-side tumours. Multivariate analysis revealed that the significant independent risk factors for dMMR-related CRC were younger age (OR: 0.979, 95% CI: 0.960–0.998), larger tumour diameter (OR: 1.313, 95% CI: 1.162–1.484), poor differentiation, no peripheral nerve invasiveness (OR: 3.018, 95% CI: 1.258–7.239), right-side colon cancer (OR: 10.821, 95% CI: 4.895–23.922), Bcl-2 positivity (OR: 0.209, 95% CI: 0.095–0.458), topoisomerase II negativity (OR: 3.333, 95% CI: 1.563–7.103) and glutathione S-transferase (GST) negativity (OR: 1.748, 95% CI: 1.009–3.027).ConclusionsYounger age, poorly differentiated tumours, negative peripheral nerve invasiveness, right-side tumours, Bcl-2 positivity, topoisomerase II negativity and GST negativity increased the likelihood of dMMR in Chinese patients with sporadic CRC.

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.

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.

Comparative immunohistochemical study of Bcl-2 and CD138 in odontogenic keratocyst, ameloblastoma, and radicular cyst, considering WHO classification

Background Odontogenic keratocyst (OKC) is one of the odontogenic lesions that have been recently classified as a developmental cyst in the last WHO odontogenic classification in 2017, despite its clinical aggressiveness and relative rate of recurrence. Aim The aim of the current work was to assess and compare OKC with both ameloblastoma (AM) and radicular cyst (RC) in relation to immunohistochemical expression of Bcl-2 and CD138. Materials and methods This is a retrospective study that included 15 cases of OKC, 20 cases of AM, and 15 cases of RC. Immunohistochemical technique was applied to detect and compare Bcl-2 and CD138 expressions in these lesions. Results For Bcl-2, 86.6% of the OKC cases and all studied AM cases (100%) were positive for Bcl-2, without significant statistically correlation (P>0.05). At the same time, OKCs were significantly correlated with RC, which were completely negative to Bcl-2 (P 0.05). Conclusion The results of the current study registered (a) positive Bcl-2 expression in OKC and AM compared with negativity of RC; (b) increased CD138 epithelial expression in OKC and RC than in AM; and (c) increased stromal CD138 expression in both OKC and AM than RC. These results reflect difference in their growth profile and invasive behavior. At the same time, it elucidates that molecular defect in Bcl-2 and CD138 protein is critical for biology of studied odontogenic lesions with consequently effect on their diagnosis and treatment. However, the localization of Bcl-2 expression supports the classification of OKC as a neoplastic one rather than a developmental cyst, in contrary to the new WHO classification. So, further studies with markers panel are recommended for more understanding of the biological nature of OKC.

ORAL PSEUDOLYMPHOMA: A DIAGNOSTIC CHALLENGE

Pseudolymphoma (PL) is a benign reactive lymphoproliferative disease secondary to known or unknown stimuli mimicking a lymphomatous-appearing picture with potential misdiagnosis of overt lymphoma. A 64-year-old white man was referred for evaluation of ulceration on the left side of the buccal mucosa with 1 week of duration. The medical history revealed Alzheimer disease treated with donepezil and vildagliptin. Regional lymphadenopathy was absent and computerized tomography (CT) scans did not show alterations. An incisional biopsy was performed and microscopic analysis showed foci of angiocentric and perivascular lymphoid infiltrate containing atypical cells surrounded by fibrous stroma. Immunohistochemical analysis revealed positivity for CD3, CD4, CD25, and FOXP3. There was weak positivity for CD10 and BCL2. Almost all atypical cells were Ki-67 positive. Epstein-Barr virus-encoded RNA 1 and 2 (EBER1, EBER2) was negative. Complete blood counts and serology for herpes simplex virus 1 and 2 (HSV1, HSV2), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were noncontributory. Four weeks after biopsy, the lesion disappeared, without treatment or modification or discontinuation of medications. A diagnosis of idiopathic PL was made. Pseudolymphoma (PL) is a benign reactive lymphoproliferative disease secondary to known or unknown stimuli mimicking a lymphomatous-appearing picture with potential misdiagnosis of overt lymphoma. A 64-year-old white man was referred for evaluation of ulceration on the left side of the buccal mucosa with 1 week of duration. The medical history revealed Alzheimer disease treated with donepezil and vildagliptin. Regional lymphadenopathy was absent and computerized tomography (CT) scans did not show alterations. An incisional biopsy was performed and microscopic analysis showed foci of angiocentric and perivascular lymphoid infiltrate containing atypical cells surrounded by fibrous stroma. Immunohistochemical analysis revealed positivity for CD3, CD4, CD25, and FOXP3. There was weak positivity for CD10 and BCL2. Almost all atypical cells were Ki-67 positive. Epstein-Barr virus-encoded RNA 1 and 2 (EBER1, EBER2) was negative. Complete blood counts and serology for herpes simplex virus 1 and 2 (HSV1, HSV2), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were noncontributory. Four weeks after biopsy, the lesion disappeared, without treatment or modification or discontinuation of medications. A diagnosis of idiopathic PL was made.

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.