Immunhistochemical Expression Research Articles

FRI370 Hyperthyroidism And Acromegaly In A Patient With A Mature Plurihormonal PIT1 Lineage PitNET/Adenoma

Abstract Disclosure: D. Slack: None. A.C. Levine: None. Background: TSH- and GH-secreting pituitary neuroendocrine tumors (PitNETs) are both rare entities, with an incidence of 1 per million people and 1-4 per million people, respectively. Thyrotroph, somatotroph, and lactotroph cells have the same progenitor, regulated by the PIT1 transcription factor. Thus, it is not unusual for PIT1 positive tumors to exhibit immunhistochemical expression of TSH, GH, and prolactin. It is vanishingly rare, however, for these tumors to secrete multiple biologically active hormones with apparent clinical sequelae. We herein report on a case of a patient with a plurihormonal PIT1 lineage PitNET secreting prolactin with secondary amenorrhea, TSH causing central hyperthyroidism and GH resulting in acromegaly. Clinical Case: A 42-year-old woman with a 1-year history of amenorrhea presented with 3 months of progressive weight loss, fatigue, palpitations, and tremulousness. She was found to have central hyperthyroidism, with an elevated free T4 (>7.77 ng/dL, nl 0.82 – 1.77) and inappropriately normal TSH (3.25 uIU/mL, nl 0.45 – 4.5). Full endocrine workup confirmed central hyperthyroidism with elevated free T4 (5.02 ng/dL) and TSH (4.68 uIU/mL) and also demonstrated hyperprolactinemia (122 ng/mL, nl 4.8 – 23.3 ng/mL), elevated IGF-1 (795 ng/mL, nl 91 – 308 ng/mL), GH (19 ng/mL, nl 0 – 10) and free alpha subunit (28 ng/mL, nl <1.02). Over the ensuing 4 months, she noted enlargement of her lips, nose, feet, and hands. MRI demonstrated a pituitary macroadenoma measuring 2.2 cm x 2.7 cm x 2 cm with asymmetric extension into the left cavernous sinus and mild elevation of the adjacent optic chiasm. She underwent an uncomplicated transsphenoidal resection of the tumor with no residual tumor noted on post-op MRI. Discharge medications were hydrocortisone 10 mg AM and, 5 mg early afternoon and levothyroxine 50 mcg daily. One month postoperatively, labs were notable for a low TSH (0.16 mIU/L), normal free T4 (1.62 ng/dL), down-trending IGF-1 (339 ng/mL), and normal prolactin (15.1 ng/mL). Additionally, AM cortisol and ACTH levels remained normal after holding her morning dose of hydrocortisone. She reported resolution of all presenting symptoms of thyrotoxicosis as well as decreasing size of her hands, feet, and nose. Pathology revealed a mature plurihormonal PIT1-lineage PitNET, with immunoreactivity for PIT1, GH, TSH, and prolactin and MIB-1 index of 3%. Conclusion: This case demonstrates the potential for PitNETs to secrete multiple biologically active pituitary hormones, including prolactin, TSH and GH, highlighting the importance of maintaining an index of suspicion for pituitary causes in the evaluation of thyrotoxicosis and of considering the plurihormonal potential of PitNETs in patients presenting with multiple endocrinopathies. Presentation: Friday, June 16, 2023

Assessment of immunhistochemical expression of CD44 and osteopontin in colorectal carcinoma

Assessment of immunhistochemical expression of CD44 and osteopontin in colorectal carcinoma

Immunohisto Chemical Expression of IDH1, ATRX and P53 in Low Grade Diffuse Gliomas at Armed Forces Institute of Pathology, Rawalpindi

Objective: To determine the immune histochemical expression of IDH1, ATRX and p53 in low-grade diffuse gliomas.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Jan to Jun 2020.
 Methodology: Forty-two cases of low-grade diffuse glioma were included in the study. The cases were stratified into diffuse astrocytoma and oligodendroglioma based on results of immunohistochemistry expression for IDH1, ATRX and p53.
 Results: The frontal lobe was the most commonly affected site 14 (33.3%). Based on the results of immunohistochemistry expression, 26 cases (61.9%) were diagnosed as an oligodendroglioma, while 16 cases (38.1%) were diagnosed as diffuse astrocytoma. All cases were assigned who grade II out of IV. In oligodendrogliomas, all cases (100%) were IDH1 mutants with the retained expression of ATRX and wild type expression of p53. Among the 16 cases of diffuse astrocytoma, IDH1 was mutant in 12 cases (75%), ATRX expression was lost in all cases, and p53 was mutant in 6 cases (37.5%).
 Conclusion: The study showed that low-grade diffuse gliomas could be stratified and sub-classified in accordance with the World Health Organization (WHO) classification of CNS tumours (2016) successfully by application of immunohistochemistry for IDH1, ATRX and p53.

The therapeutic prospect of zinc oxide nanoparticles in experimentally induced diabetic nephropathy

ABSTRACT Diabetic nephropathy (DN) is the most frequent cause of end-stage renal failure. Zinc oxide nanoparticles (ZnO-NPs) are promising antidiabetic agents. Our aim was to evaluate the prospective efficacy of ZnO-NPs in treating DN in streptozotocin-induced diabetic rats. Rats were randomly dispersed into three sets: control group, DN group and DN + ZnO-NPs group. ZnO-NPs were given at a dose of 10 mg/kg/day by oral gavage for 4 weeks. Urine and blood samples were processed for biochemical analyses. Kidney samples were managed for light and electron microscopy studies. Immune histochemical staining of P53, aquaporin11 (AQP11) and mechanistic target of rapamycin (mTOR) were performed. Gene analyses of nephrin, podocin, beclin-1, LC3 and p62 were done. Administration of ZnO-NPs ameliorated the functional and histopathological alterations of the kidney in a rat model of diabetic nephropathy. ZnO-NPs retained the constancy of the glomerular filtration barrier and restored almost normal renal structure. This was confirmed by upregulation of mRNA expression of podocyte markers (nephrin and podocin) and AQP11 immune histochemical expression in the renal tubules. The beneficial outcomes of ZnO-NPs might be attributed to activation of autophagy through inhibiting mTOR signaling pathway. ZnO-NPs enhanced beclin-1 and LC3 mRNA expressions and reduced p62 mRNA expression. ZnO-NPs also exerted anti-apoptotic potential (evidenced by the decrease in p53 immune expression), anti-inflammatory and anti-oxidant effect [endorsed by suppression of serum cyclooxygenase-2 (COX-2) enzyme activity, tissue nuclear factor kappa beta (NF-κB) level and blood hypoxia-inducible factors (HIF-1α) level]. These results may point the way to an effective therapy of DN. Abbreviations: AQP11 Aquaporin11; BUN: Blood urea nitrogen; COX-2: Cyclooxygenase-2; DAB: 3, 3’-diaminobenzidine; DM: Diabetes mellitus; DN: Diabetic nephropathy; ELISA: Enzyme-linked immunosorbent assay; H&E: Hematoxylin & eosin; HIF-1α: Hypoxia-inducible factors; iNOS: inducible nitric oxide synthase; LC3: Microtubule-associated protein 1 light chain 3; mTOR: Mechanistic target of rapamycin; NF-κB: Nuclear factor kappa beta; NPs: Nanoparticles; PAS: Periodic acid Schiff; PCR: Polymerase chain reaction; PGE2: Prostaglandin E2; ROS: Reactive oxygen species; STZ: Streptozotocin; X ± SEM: Mean ± standard error of means; Zn: Zinc; ZnO-NPs: Zinc oxide nanoparticles.

The effects of calcitonin on post-orthodontic relapse in rats.

ObjectivesTo determine the effects of systematic calcitonin administration on post‐orthodontic relapse in rat model.Material and methodsThis experimental animal model involved 36 male Wister rats. The maxillary right first molars were moved mesially, using a modified orthodontic appliance delivered 50 gm, for 14 days, retained for 4 days and left to relapse for 10 days. The study group was divided into three subgroups in which a single injection of calcitonin (20 IU/Kg), three injections of calcitonin (20 IU/Kg), each every other day, and normal saline were administered subcutaneously after orthodontic tooth movement has finished. The relapse ratio, histomorphometric analysis including osteoblasts, osteoclasts numbers and bone area and immunohistochemical analysis including the expression of receptor activator of nuclear factor kappa Β (RANK), receptor activator of nuclear factor kappa Β ligand (RANKL) and osteoprotegerin (OPG) were measured and assessed.ResultsThe relapse ratio was significantly reduced in the three‐dose calcitonin group (28%) compared to the single dose calcitonin group (34%) and the control group (46%). This was accompanied by a nonsignificant increase in osteoblasts number and bone area in three‐dose calcitonin group and a nonsignificant reduction in osteoclast number. However, the immune histochemical expression of RANK, RANKL and OPG did not show statistically significant difference at the end of relapse period.ConclusionsSystemic administration of three doses of calcitonin may minimize the relapse ratio in experimentally moved rat molars.

Association between ki67 and PR Expression in Grades of Meningioma and its Prognosis

Introduction: Meningioma is the very important type of tumor that occur in central nervous system (CNS)that represented 1/3 of whole tumor of CNS. In USA 97/100,000, persons recorded have meningioma. With170,000 patients detected as meningioma. The aim of study is the aim of the present study is to evaluate theuse of immunhistochemical expression of PR and ki67 for predicting the grades of meningioma, which areimportant in their prognosis, and line of treatment.Method: Ninety patients with meningioma were collected from the Neurosurgical Hospital-Baghdad, duringthe period from January 2017 to January 2020. The data for cases were collected to study the age, genderand grade of tumor. Staining hematoxylin/Eosin (H plus E) for histological inputting and classifying of thetumors and immunohistochemically workup for PR & Ki67 done.Results: Cross sectional study for 90 patients with age, mean (44 ± 12) years old, in current study 64% ofpatients was females and 36% of patients was males, strong positive PR expression represented 50% ofpatients, 79% of patients have low Ki 67, 15% of them have intermediate Ki67 and 6% of patients with highKi67. Most of patients with age group 40-59 years old (51%). The mean and SD of Ki67 in (%) accordingto grades of meningioma I, II and III as following: (0.3 ± 0.07), (7 ± 5.9) and (38 ± 0.07) respectively.There is significant association between grades of meningioma and PR expression; 71% of grade I withPR expression strongly positive, 23% of grade II with PR expression were weakly positive and 100% ofgrade III with PR expression were negative. In addition, there is significant association between grades ofmeningioma and prognosis; 100% of grade I with good prognosis, 100% of grade II with fair prognosis and100% of grade III with poor prognosis. In current study, also there is significant association between gradesof meningioma and Ki67; 100% of grade I with low level of Ki67, 100% of grade III with high level of Ki67and 64% of grade II with intermediate level of Ki67. There is no significant association between age andgender with grades of meningioma.Conclusion: The mean Ki-67 was significantly more in meningioma grade III than in patients with gradesII and I as WHO classification. There is strong expression of PR was found mainly in the grade I typicalmeningioma group. Utilization of markers for proliferation (ki-67 labeling index) and hormonal expression(Progesterone Receptor) in combination with histopathological features may help in the identification ofbiologically aggressive meningioma.

Relationship between Supernatant Cytokines and Expression of Epithelial-Mesenchymal Transition Markers in Biopsy Samples of Invasive Breast Carcinoma of No Special Type with Lymphatic Spread of Metastasis

The relationship between the content of supernatant cytokines and the immune histochemical (IHC) expression of epithelial-mesenchymal transition (EMT) markers was studied in biopsy samples of invasive breast carcinoma of no special type (IBC-NST) from patients with and without lymphatic spread of metastases (group II and group I, respectively). The concentrations of TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, MCP-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, and IL-1Ra, as well as the immunohistochemical (IHC) expression of EMT markers cadherin-E (CDH1), β-1 integrin (CD29) and type II collagen (CII) were assayed. Results have shown that the patients of these groups statistically significantly differed by spontaneous production of IL-18 and G-CSF, and by the index of the polyclonal activator influence (IPAI) on G-CSF production. The study of relationships between supernatant cytokine production and the IHC expression by biopsy samples revealed correlations between the parameter of CII expression in the tumor tissue and the cytokine production by tumor biopsy specimens; these correlation links were typical for all IBC-NST patients, while correlation links (both direct and reverse ones) between CDH1, CD29, and cytokine production varied in groups of patients with and without lymphatic spread of metastases. The study revealed the features of the correlation links between the cytokine production by the tumor, its microenvironment and the IHC expression of EMT markers in IBC-NST patients with and without lymphatic spread of metastasis.

The mismatch repair system is not affected in medullary thyroid carcinoma independent of stromal desmoplasia or ret proto-oncogene mutation

IntroductionMedullary thyroid carcinoma (MTC) is an aggressive neuroendocrine neoplasia of the thyroid with 10 year overall survival of 50% and limited therapeutic options. High tumor mutational burden because of microsatellite instability (MSI) seems to be a predictor of response to immune checkpoint inhibitor therapy in different tumors. Therefor in 2017 the U.S. Food and Drug Administration (FDA) permitted the therapy of solid tumors with proven Microsatellite instability (MSI) with PD1 antibody Pembrolizumab independently of their origin. As little is known about MSI in MTC and new therapeutic strategies would be eligible we tried to find out, if therapy with PD1-inhibitors could be promising. Material and methodsWe performed MSI-analyses of 38 cases of MTC. Included were MTCs with and without stromal desmoplasia and with/without lymph node metastases. We also checked the immunhistochemical expression of PD-L-1 and performed next generation sequencing for genetic alterations. ResultsAll cases revealed stable conditions of the microsatellites and showed immunohistochemically positive staining of the four mismatch repair proteins. PD-L-1- Immunostaining was negative in all cases. DiscussionOur data show there is no MSI in MTCs, irrespectively of their status of desmoplasia, metastases and/or ret-mutation. Therefore a positive effect of PD1 inhibitors, because of MSI-associated high tumor mutational burden, seems to be unlikely.

The potential of mangosteen (Garcinia mangostana) peel extract, combined with demineralized freeze-dried bovine bone xenograft, to reduce ridge resorption and alveolar bone regeneration in preserving the tooth extraction socket.

Background:Following the extraction of a tooth, bone resorption can cause significant problems for a subsequent denture implant and restorative dentistry. Thus, the tooth extraction socket needs to be maintained to reduce the chance of any alveolar ridge bone resorption.Objective:The objective of this study is to determine whether the administration of mangosteen peel extracts (MPEs), combined with demineralized freeze-dried bovine bone xenograft (DFBBX) materials for tooth extraction socket preservation, could potentially reduce inflammation by decreased the expression of nuclear factor κβ (NfKb) and receptor activator of nuclear factor-κβ ligand (RANKL), to inhibit alveolar bone resorption, and increased of bone morphogenetic protein-2 (BMP2) expressions to accelerate alveolar bone regeneration.Materials and Methods:This study consists of several stages. First, a dosage of MPE combined with graft materials was applied to a preserved tooth extraction socket of a Cavia cobaya. Second, the C. cobaya was examined using immune histochemical expression of NfKb, RANKL, BMP2, as well as histology of osteoblasts and osteoclasts. The research was statistically analyzed, using an analysis of variance test and Tukey honest significant difference test.Results:The results of this research were that it was determined that MPEs combined with graft materials on a preserved tooth extraction socket can reduce NfKb, RANK, and osteoclasts also increase of BMP2 and osteoblast.Conclusion:The induction of MPEs and DFBBX is effective in reducing inflammation, lowering osteoclasts, decreasing alveolar bone resorption, and also increasing BMP2 expression and alveolar bone regeneration.

Cell Surface Expression of 70 KDa Heat Shock Proteins and P21 in Normal Oral Mucosa , Oral Epithelial Dysplasia and Squamous Cell Carcinoma : An Immunohistochemical Study

Background: Oral SCC is a complex malignancy where environmental factors, viral infections and genetic alterations most likely interact, and thus give rise to the malignant condition. The HSP70 play a direct role in apoptosis inhibition by aligning the improved integrity of a cell’s proteins with the improved chances of that particular cell’s survival.P21 gene produces p21 protein which is a potent cyclin-dependent kinase inhibitor that plays a significant role in carcinogenesis. The aims of the study were to evaluate and compare the immun-histochemical expression of the HSP70 and cell cycle protein p21in NOM, OED, and OSCC. Correlate both marker expressions with each other. Materials and methods: Forty six formalin-fixed, paraffin embedded tissue blocks(10 cases of normal oral mucosa,16 cases of oral epithelial dysplasia, and 20 cases of oral squamous cell carcinoma) were included in this study, an immunohistochemical staining was performed using antiHSP70monoclonalantibody, and anti p21 monoclonal antibody. Results: Positive IHC expression ofHSP70 was found in 2 cases (20%) of NOM, 13 cases (81.3%) of OED and in 16 cases (85%) of OSCC. Positive IHC expression of P21 was detected In NOM in 2 cases (20%), while it was found in 9 cases (56.2%) of OED, and in 14 cases (70%) of OSCC .The difference between the expressions of both markers was statistically significant in NOM, highly significant in OED, and OSCC. Conclusions: This study signify the important role of HSP70 and p21in oral carcinogenesis and in the evolution of the mucosa from normal to dysplastic to invasive carcinoma

Establishment of a logistic regression model for the predicting of radio-sensitivity of preoperative radiotherapy in rectal cancer

Objective To investigate the correlation between the biomarkers related to radio-sensitivity and preoperative radiotherapy in rectal cancer patients, and to establish a logistic regression model to predict the effect of the preoperative radiotherapy through detecting the expression levels of the molecular markers. Methods 33 patients with rectal cancer who received preoperative radiotherapy from January 2010 to January 2015 were retrospectively analyzed. Patients' information was also collected including the serum level of carcino-embryonic antigen(CEA), the immune-histochemical expression levels of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), thymidylate synthase (TS) and Ki-67, and image data (CT or magnetic resonance imaging) before radiotherapy, preoperative clinical staging and the postoperative pathologic staging. According to the postoperative pathological remission, the treatment effects of preoperative radiotherapy included effective (CR+PR) and ineffective (PD+SD) were evaluated. The relationship between these molecular markers and the curative effect of preoperative radiotherapy was analyzed by logistic regression analysis using SPSS v17.0 software, and a logistic curative effect prediction model was established. Results As a result of single factor and multiple factors logistic binary regression analysis, CEA, VEGF and Ki-67 were recognized as the interested factors for the radio-sensitivity predicting in patients with rectal cancer who received preoperative radiotherapy. A molecular markers predictive model for radio-sensitivity in preoperative radiotherapy in rectal cancer is as follow: log P=1.700-0.276×CEA-0.238×VEGF-0.135×EGFR+1.377×TS+0.080×Ki-67. Serum CEA level and the expression of VEGF might associate with radio-resistant, and the expression of Ki-67 might associate with better reaction to preoperative radiotherapy. Conclusion The levels of serum CEA, VEGF and Ki-67 may be the predictors of radio-sensitivity in rectal cancer patients who received preoperative radiotherapy. Key words: Rectal neoplasms; Radiotherapy; Tumor markers, biological; Radiation tolerance

LG-40UNUSUAL NON-PILOCYTIC HISTOPATHOLOGICAL FEATURES OF PEDIATRIC INFRATENTORIAL GLIOMAS WITH BRAF FUSION GENE: A REPORT OF 2 CASES

LG-40. UNUSUAL NON-PILOCYTIC HISTOPATHOLOGICAL FEATURES OF PEDIATRIC INFRATENTORIAL GLIOMAS WITH BRAF FUSION GENE: A REPORT OF 2 CASES Christine Haberler1, Andreas Kiefer2, Barbara Jauk2, Christian Dorfer1, Thomas Czech1, Giles Vince2, Manuela Badiali3, and Irene Slavc1; Medical University of Vienna, Vienna, Austria; Academic Hospital of Klagenfurt, Klagenfurt, Austria; Microcitemico Hospital, Cagliari, Italy Genomic profiling studies have unraveled distinct molecular changes in different pediatric glioma entities. High grade gliomas commonly harbor H3F3A mutations or PDGFRA amplifications, diffuse low grade gliomas frequently display mutations in the FGFR1 or MYB1 gene, and pilocytic astrocytomas are characterized by MAPK pathway alterations including BRAF fusions and mutations. We report two infratentorial tumors with unusual morphological features. Patient 1 is a 15-year-old girl with a 6 months history of headache and a 4.5x4.5x6 cm cerebellar cystic tumor with contrast enhancement. A near gross total resection was performed. Histopathologically, the tumor was partly clear-celled but showed focally also some rosettes reminiscent of a RGNT. Vascular proliferations in a nonpilocytic tumor raised the suspicion of a malignant glioma. Patient 2, a 4-year-old girl presented with cephalea/strabism and had a cystic 2,8 x 2,9 x 2,5 cm tumor in the pineal region, radiologically compatible with a pilocytic astrocytoma. A gross total resection was performed. Histopathologically, ependymoma-like features with perivascular pseudorosettes, clear cells and vascular proliferations were present. In both cases immunhistochemical expression pattern confirmed a glioma without H3F3A K27M and BRAF V600E mutation, however classification and grading were difficult. Sequencing revealed in both tumors a KIAA1549– BRAF fusion. As this alteration is predominantly but not exclusively found in pilocytic astrocytomas and histopathologically no clear-cut signs ofmalignancy werepresent, no adjuvant treatment was administered. Both patients show no tumor recurrence/progression 32 and 21 months postoperatively. These cases emphasize the importance of molecular analyses in tumors with unusual morphological feature. Neuro-Oncology 18:iii78–iii96, 2016. doi:10.1093/neuonc/now075.40 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Case report: Cushing's disease

A 49-year obese woman (BMI 46,6 kg/m2) with diabetes mellitus type 2 and hypertension was referred to our clinic to take part in our program for weight reduction. At presentation the woman showed typical clinical signs of Cushing's syndrome. Basal levels of cortisol and ACTH didn't show any abnormalities, however ACTH was in the upper range. Cortisol was inadequately suppressed after 2 mg dexamethasone. To ensure correct implementation, testing was repeated with inadequately suppression of cortisol again. Measurement of urinary cortisol excretion over 24h showed an elevated quantity. Intravenous application of 100 µg CRH led to an increase of ACTH > 50% and also cortisol rose slightly. The assessment of the testing results pointed to Cushing's disease. NMR of the pituitary gland brought further clearness by showing an adenoma of 11 × 17 × 13 mm. Additional testing of the other pituitary axes showed no insufficiency. The woman was then directed to a neurosurgical departement and transsphenoidal resection of the pituitary adenoma was accomplished. Due to invasive growth into the sinus cavernosus on both sides, an incomplete resection could not be certainly excluded by the surgeon. Histology showed an invasive adenoma with immunhistochemical expression auf ACTH. Unfortunately no remission of disease activity was achieved. So radiotherapy was performed. To bridge the time until the effect of radiotherapy sets in, we began a medical therapy with pasireotide, up to 900 µg twice daily. In the following months medical therapy had to be intensified by adding cabergoline und ketoconazole. This resulted in disease control over several months. But finally hypercortisolism worsened again so that bilateral adrenalectomie was performed.

Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer - overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression

BackgroundIn breast cancer, the role of epigenetic alterations including modifications of the acetylation status of histones in carcinogenesis has been an important research focus during the last years. An increased deacetylation of histones leads to increased cell proliferation, cell migration, angiogenesis and invasion. Class 1 histone deacetylases (HDAC) seem to be most important during carcinogenesis.MethodsThe immunhistochemical expression of HDAC1, 2 and 3 was analyzed on tissue microarrays (TMAs) from 238 patients with primary breast cancer. We analyzed the nuclear staining intensity (negative, weak, moderate, strong) as well as the percentage of positive tumor cells and calculated the immunoreactivity score (0–12). Expression was correlated with clinicopathological parameters and patient survival.ResultsIn this cohort, we found a differential positive expression of HDAC1, HDAC2 and HDAC3. HDAC2 and HDAC3 expression was significantly higher in less differentiated tumors: HDAC2 (n=207), p<0.001 and HDAC3 (n=220), p<0.001 and correlated with negative hormone receptor status: HDAC2 (n=206), p=0.02 and HDAC3 (n=219), p=0.04. Additionally, a high HDAC2 expression was significantly associated with an overexpression of HER2 (n=203, p=0.005) and the presence of nodal metastasis (n=200, p=0.04).HDAC1 was highly expressed in hormone receptor positive tumors (n=203; p<0.001).ConclusionAs a conclusion, our results show that the class-1 HDAC isoenzymes 1, 2 and 3 are differentially expressed in breast cancer. HDAC2 and HDAC3 are strongly expressed in subgroups of tumor with features of a more aggressive tumor type.

An Analysis of the Expression of Bcl-2, Podoplanin and Lymph Angiogenesis in Benign and Malignant Salivary Gland Tumours

Background: Salivary gland tumours comprise a significant proportion of oral tumours and are the next common neoplasm of the mouth after squamous cell carcinoma. These neoplasm’s have widely variable histopathologic and biologic characteristics, which makes it difficult to determine the pathogenesis and selection of therapeutic modalities. Alteration in some proto-oncogenes and tumour suppressor genes may lead to the development and progression of these tumours. Aim: The purpose of this study was to analyze the immune histochemical expression of Bcl-2 and epithelial podoplanin and lymph angiogenesis in benign and malignant salivary gland tumours. Material and method: The sample consisted of 20 formalin-fixed paraffin embedded blocks of benign and malignant salivary glands tumours. Immunohistochemical staining procedure was performed using monoclonal anti Bcl-2 antibody and D2-40 antibody. The sections were evaluated for Bcl-2 and epithelial podoplanin expression and D2-40 positive lymphatic vessels. Results and conclusion: Bcl-2 showed positive immune expression in all benign and malignant salivary gland tumours with mucoepidermoid carcinomas showing most intense expression. Podoplanin immunostaining was also assessed, highest recorded score was in peripheral mucoepidermoid carcinoma (10.4? 3.05). Lymphatic micro vessel density expressed by podoplanin showed intense score in central mucoepidermoid carcinoma (5.05? 5.0). Present investigation demonstrated positive Bcl-2, podoplanin response and Lymphatic micro vessel density in both benign and malignant salivary gland tumours suggesting that Bcl-2 and podoplanin alteration may be associated with the progression of these neoplasms.

Immunhistochemical expression of galectin-3 in cancer: a review of the literature

Galectin-3 is a β-galactoside-binding animal lectin that contains carbohydrate-recognition domains and displays multiple related functions. It has important roles in diverse biological events, such as embryogenesis, growth, cell adhesion, proliferation, differantiation, cell-cycle progression, apoptosis, mRNA splicing, and regulation of the immune system. Galectin-3 is expressed in various cells and tissues, such as activated macrophages, eosinophils, neutrophils, mast cells, epithelium of the gastrointestinal and respiratory tracts, kidneys and some sensory neurons, and is also involved in tumorigenesis, angiogenesis, and tumor metastasis. In this review of the literature, immunohistochemical Galectin-3 expression is investigated in numerous tumors and disorders of various organ systems.

LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett's Esophagus?

BackgroundInvestigation of the expression of an intestinal stem cell marker in esophageal adenocarcinomas (EAC) with and without Barrett's Esophagus (BE), with respect to a cancer stem cell (CSC) hypothesis.Materials and methodsExpression of a putative intestinal stem cell marker LgR5 was analyzed in esophageal cancer specimen (n = 70: 41 EAC with BE, 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC) and in the adenocarcinoma cell line OE-33. Ki-67 and Cdx-2 were co-labelled with LgR5 in double staining experiments. Immunhistochemical expression results were confirmed by RT-PCR and correlated with tumor stage and five-year survival rates.ResultsLgR5was found expressed in 35 of 41 (85%) EAC with BE and in 16 of 19 (81%) EAC without BE. By contrast, LgR5 was not found to be expressed in ESCC. Quantification of immunolabeling showed 15% LgR5+ cells in EAC with BE, 32% LgR5+ cells in adjacent BE and 13% in EAC without BE. Immunofluorescence double staining experiments with LgR5 and Ki-67 revealed a subpopulation (~5%) of proliferating LgR+/Ki-67+ cells. On mRNA-level, expression of LgR5 was higher in BE in comparison to EAC (p = 0.0159). High levels of LgR5 expression in BE associated EAC were associated with poorer survival in univariate analysis.ConclusionThe stem cell marker LgR5 is expressed in EAC, irrespective of association with BE, and appears to have negative impact on survival. The subset of proliferating LgR5+ cells (<5%) might resemble rapidly cycling CSCs, which needs to be substantiated in further investigations.