scholarly journals Clinicopathological and Immunohistochemical Analysis of 21 cases of Traumatic Ulcerative Granuloma with Stromal Eosinophilia Using CD30, CD68 and TGF-β1

2018 ◽  
Vol 30 (4) ◽  
pp. 45-53
Author(s):  
Mustafa B Al-Talqani ◽  
Bashar H Abdullah ◽  
Ameer D Hameedi
Keyword(s):  
Lymphoproliferative Disorder ◽  
Mononuclear Cells ◽  
Immunohistochemical Analysis ◽  
Excisional Biopsy ◽  
Clinicopathological Parameters ◽  
Ulcerative Lesion ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
High Level ◽  
Tgf Β1

Background: Traumatic ulcerative granuloma with stromal eosinophilia is an impressive benign chronic ulcerative lesion of the oral mucosa with vague etiopathogenesis. It was supposed to represent an oral counterpart of primary cutaneous CD30+ lymphoproliferative disorder. Histopathologically, it is characterized by mixed inflammatory infiltrate predominated by histiocytes, lymphocytes and eosinophils along with presence of scattered large atypical mononuclear cells. It has worrisome clinical presentation. It may heal spontaneously, but in most occasions it persists and never heal unless removed surgically (incisional or excisional biopsy). A rare subset may show worrisome immunohistochemical features. Follow up is highly recommended. Materials and methods: Formalin fixed - paraffin embedded tissue blocks of twenty-one cases were cut and mounted on positively charged slides and stained by primary antibodies (CD30, CD68 and TGF-β1). A statistical analysis was performed between the immunohistochemical scores for markers with each other and with clinicopathological parameters (age, sex, size of ulcer, number of eosinophils and mitoses). Results: The age of the patients ranged from 20 to 72 years, with a higher female propensity. Immunohistochemical positive expression for CD30 (16 case) mainly involved round small lymphocytes, while all cases were positive for CD68 and TGF-β1. Statistically, there was no significant relation between the scores of CD30, CD68 and TGF-β1 with each other and with the aforementioned parameters, (P<0.05). The eosinophils count showed a significant positive correlation with age (P=0.008), size of ulcer (P=0.007) and mitoses (P=0.004). Conclusion: Traumatic ulcerative granuloma with stromal eosinophilia is a benign and reactive chronic oral ulcerative lesion rather than being CD30+ lymphoproliferative disorder; this conclusion is supported by heterogeneous, focal and nonspecific staining for CD30 and being typically infiltrated by CD68+ macrophages. Whereas, a high level of expression for TGF-β1 indicated that the aforementioned factor was not associated with the delayed healing of this lesion

PD-L1 expression, tumor mutational burden, and microsatellite instability status in 746 pancreas ductal adenocarcinomas.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 757-757
Author(s):  
Amanda Hemmerich ◽  
Claire I. Edgerly ◽  
Daniel Duncan ◽  
Richard Huang ◽  
Natalie Danziger ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Mutational Burden ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Comprehensive Genomic Profiling ◽  
Tumor Mutational Burden ◽  
Positive Score ◽  
Combined Positive Score ◽  
High Level ◽  
Positive Groups

757 Background: Pancreas ductal adenocarcinomas (PDA) has a 5-year survival rate of 6% with a need for new therapeutic options. The approval of pembrolizumab for some gastrointestinal cancers shows the potential of immunotherapy (IMT) in PDA. We evaluated the IMT-associated biomarkers of PD-L1 expression, tumor mutational burden (TMB), microsatellite instability (MSI) and PD-L1 amplification in PDAs. Methods: 746 formalin-fixed paraffin embedded samples were evaluated for PD-L1 IHC using the Dako 22C3 pharmDx assay and scored using tumor proportion score (TPS). The cases had comprehensive genomic profiling (CGP) via DNA sequencing, using a hybrid-capture next-generation sequencing assay (FoundationOne and FoundationOneCDx) for genomic alterations (GAs), TMB, and MSI. Results: PD-L1 was positive (TPS ≥ 1%) in 29% (214/746) and negative in 71% (532/746). 43/214 (20%) of positive cases were high positive (TPS ≥ 50%). TMB (590 cases) had a mean of 3.20, 3.46, and 3.61 mutations/Mb for PD-L1 negative, positive, and high positive groups. 3 hypermutated (TMB ≥ 20) were negative for PD-L1 expression. 3/581 cases were MSI-high with a high TMB score (average 23.53 mutations/Mb). 2 MSI-high cases were negative for PD-L1 and 1 was high positive. PD-L1 amplification was not detected (0/746). Only BCOR was significantly different between PD-L1 high positive and PD-L1 negative tumors (Table). Conclusions: Of 729 PDA cases, 29% were positive (TPS ≥ 1%) for PD-L1 expression while only 6% of all cases showed a high level of PD-L1 expression on tumor cells. TMB high (3/729) and MSI-High (3/729) cases were rare. Only 2 of the TMB high cases were also MSI-high. PD-L1 amplification was not detected. Comparing GAs in PD-L1 high positive vs negative cases was only significantly different for BCOR. Further investigation is needed to see if a combined positive score of PD-L1 expression may identify a subset of patients with PDA who are more likely to respond to IMT. [Table: see text]

scholarly journals Pleomorphic Adenoma versus Basal Cell Adenoma: An immunohistochemical analysis with b-catenin

2014 ◽  
Vol 17 (1) ◽  
pp. 23
Author(s):  
Renata Falchete do Prado ◽  
Camila Lopes Cardoso ◽  
Alberto Consolaro ◽  
Antonio Luis Assis Taveira
Keyword(s):  
Basal Cell ◽  
Immunohistochemical Analysis ◽  
Myoepithelial Cells ◽  
Complex Method ◽  
Nuclear Staining ◽  
Cell Adenoma ◽  
Formalin Fixed Paraffin ◽  
Pleomorphic Adenomas ◽  
Formalin Fixed Paraffin Embedded ◽  
Degree Of Differentiation

<p>The objective of this study was to investigate the distribution of b-catenin in pleomorphic adenomas and the basal cell adenomas to<strong> </strong>clarify its possible role in the etiopathogenesis of these two lesions. The expression of b-catenin (BD Transduction Laboratories) was analyzed by immunohistochemistry in formalin-fixed, paraffin-embedded specimens by the avidin-biotin-peroxidase complex method in 10 pleomorphic adenomas and 2 basal cell adenomas. The specimens were analyzed taking into account intensity, distribution and association with myoepithelial cells. The results showed that  all cases of pleomorphic adenomas exhibited membranous and cytoplasmic immunostaining and the 2 cases of basal cell adenomas displayed nuclear staining. Higher b-catenin index rates were seen mainly in ductal structures of pleomorphic adenomas and in the nuclei of myoepithelial stromal and myoepithelial cells of solid clusters in basal cell adenomas. In conclusion, this immunohistochemical study may suggests the different degree of differentiation of the myoepithelial cells in these two tumors.<strong><em></em></strong></p>

PD-L1 Expression on Cell Block Preparations of Pancreatic Adenocarcinoma

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S94-S95
Author(s):  
Victoria Costa ◽  
David Kim ◽  
Melanie Johncilla ◽  
Abha Goyal ◽  
Rema Rao
Keyword(s):  
Disease Progression ◽  
Tumor Cells ◽  
Locally Advanced ◽  
Immunohistochemical Analysis ◽  
Inflammatory Cells ◽  
Fixation Method ◽  
Lung Cancers ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Combined Positive Score

Abstract Objectives Programmed death-ligand 1 (PD-L1) is an emerging molecular target in anticancer therapy, most notably non–small cell lung cancers. PD-L1 expression in pancreatic adenocarcinomas (PDAs) on surgical specimens is highly variable, with 10% to 60% of tumors showing expression. PD-L1 expression in PDA on endoscopic ultrasound-guided fine needle aspirations (EUS-FNAs) has been rarely studied. Methods Formalin-fixed, paraffin embedded (FFPE) cell blocks (CBs) from 65 EUS-FNA samples of 55 patients, with a diagnosis of PDA, with at least 20% tumor cellularity were retrieved. The cell blocks were originally fixed in CytoRich fixative. Immunohistochemical staining (IHC) for PD-L1 was performed using the M365329-1 (22C3) clone according to the manufacturer’s approved protocol and optimized for the fixation method using appropriate controls. A combined positive score (CPS) defined per CAP guidelines as the total number of positive tumor cells and inflammatory cells as a percentage of the total number of tumor cells was assessed for each case and was grouped as <1, 1-20, or >20. Results Twenty-five samples (38%) from 21 patients showed immunoreactivity to PD-L1, with 21 (32%) having a CPS of <1 and four (6%) having a CPS of 1-20. Eight of these 25 samples had surgical correlates, of which concordant staining was noted in five (62.5%). Of the discordant three, decreased tumor cell sampling in the core biopsy was noted in one. Overall, 20 of 21 patients (95%) with PD-L1 immunoreactivity had disease progression with 17 (81%) associated with metastatic disease and three (14%) with locally advanced disease. Conclusion Immunohistochemical analysis for PD-L1 is feasible on EUS-FNA CB samples when optimized and validated for the fixation method using appropriate controls. PD-L1 expression is seen in only a minority of PDAs, albeit with a very low CPS. The potential role of PD-L1 as a prognostic marker for disease progression needs further exploration.

scholarly journals APPLYING GATA3 IN DIFFERENTIATING UROTHELIAL CARCINOMA FROM PROSTATIC ADENOCARCINOMA: AN IMMUNOHISTOCHEMICAL STUDY

2018 ◽  
Vol 11 (12) ◽  
pp. 292
Author(s):  
Weam Hamzah Abdullah ◽  
Hadeel Abdulelah Kerbel ◽  
Rafid Fakhir Al Husseini
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Biology ◽  
Metastatic Carcinoma ◽  
Prostatic Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Differentiation Markers ◽  
Formalin Fixed Paraffin ◽  
Gata3 Expression ◽  
Formalin Fixed Paraffin Embedded ◽  
Differentiation Marker

Objectives: Urothelial carcinoma and prostatic adenocarcinoma are the most common tumors of genitourinary system. Both tumors can demonstrate a broad morphology or present as poorly differentiated carcinoma occurring in urinary bladder or prostate or both organs that raise the suspicion of a locally extending or metastatic carcinoma from either organs. Accurate distinction between these tumors is mandatory because of different tumor biology and therapeutic protocols. In equivocal tumor morphology, the primary option is to use immunohistochemical panel in surgical pathology that includes differentiation markers that will assist pathologists to avoid misdiagnosis. The aim of this study is immunohistochemical evaluation of GATA3 in urothelial carcinoma and prostatic adenocarcinoma with correlation to different clinicopathological parameters.Methods: We used formalin-fixed paraffin-embedded tissue blocks from 51 patients of urothelial carcinoma and 15 patients of prostatic adenocarcinoma including different grades, stages, and types. Monoclonal antibody for GATA3 was used for immunohistochemical staining of tissue sections, and GATA3 expression was semi-quantitatively scored using H-score method.Results: Of 51 urothelial carcinomas, 96% were GATA3 positive with a mean H-score = 212. No correlation between GATA3 expression and clinicopathological parameters includes grade and stage. Lower GATA3 expression was noted in urothelial carcinoma variants. All of prostatic adenocarcinoma cases did not show GATA3 reactivity.Conclusion: GATA3 reactivity is a reliable factor to confirm diagnosis of urothelial carcinoma and exclude prostatic adenocarcinoma. The routine use of GATA3 as differentiation marker for urothelial carcinoma may be advocated based on the results of this study.

scholarly journals Trail Overexpression Inversely Correlates with Histological Differentiation in Intestinal-Type Sinonasal Adenocarcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
M. Re ◽  
A. Santarelli ◽  
M. Mascitti ◽  
F. Bambini ◽  
L. Lo Muzio ◽  
...  
Keyword(s):  
Intestinal Type ◽  
Clinicopathological Parameters ◽  
Molecular Events ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Immunohistochemical Studies ◽  
The Relationship

Introduction. Despite their histological resemblance to colorectal adenocarcinoma, there is some information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). To evaluate the possible role of TNF-related apoptosis-inducing ligand (TRAIL) gene defects in ITAC, by investigating the immunohistochemical expression of TRAIL gene product in a group of ethmoidal ITACs associated with occupational exposure.Material and Methods. Retrospective study on 23 patients with pathological diagnosis of primary ethmoidal ITAC. Representative formalin-fixed, paraffin-embedded block from each case was selected for immunohistochemical studies using the antibody against TRAIL. Clinicopathological data were also correlated with the staining results.Results. The immunohistochemical examination demonstrated that poorly differentiated cases showed a higher percentage of TRAIL expressing cells compared to well-differentiated cases. No correlation was found with other clinicopathological parameters, including T, stage and relapses.Conclusion. The relationship between upregulation of TRAIL and poorly differentiated ethmoidal adenocarcinomas suggests that the mutation of this gene, in combination with additional genetic events, could play a role in the pathogenesis of ITAC.

The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer

2016 ◽  
Vol 70 (4) ◽  
pp. 331-356 ◽  
Author(s):  
Anelisa Jaca ◽  
Padmini Govender ◽  
Michael Locketz ◽  
Richard Naidoo
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Analysis ◽  
Clinicopathological Features ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Sporadic Cases ◽  
E Cadherin

AimsThe study was conducted to assess the expression levels of epithelial mesenchymal transition (EMT) proteins (E-cadherin, N-cadherin, snail-1 and vimentin) and miRNA-21. In addition, we correlated these data with clinicopathological features in Colorectal cancer.MethodsH&E slides from a total of 59 formalin fixed paraffin embedded tissue blocks were examined by a pathologist to demarcate normal and tumour regions. Immunohistochemical analysis of mismatch repair proteins (MLH1, MSH2 and MSH6) and EMT markers (E-cadherin, N-cadherin, snail-1 and vimentin) was performed. The miRNA-21 expression levels were determined using qRT-PCR and the data was analysed using the relative quantification method. The Fisher's exact and Pearson's χ2 tests were used to correlate snail-1, E-cadherin, miRNA-21 and clinicopathological data.ResultsOur results showed a statistically significant correlation between high miRNA-21 expression levels and E-cadherin positive cases. There was also an association between high miRNA-21 expression levels and negative snail-1 expression. No significant correlation was seen between miRNA-21 expression levels and clinicopathological features. Moreover, high expression levels of miRNA-21 were significantly associated with the sporadic cases.ConclusionsOur data suggest that miRNA-21 in association with E-cadherin and snail-1 does not play a significant role in the development and progression of this disease.

scholarly journals Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6036
Author(s):  
Robert Wiebringhaus ◽  
Matteo Pecoraro ◽  
Heidi A. Neubauer ◽  
Karolína Trachtová ◽  
Bettina Trimmel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proteomic Analysis ◽  
Biochemical Recurrence ◽  
Sample Selection ◽  
Immunohistochemical Analysis ◽  
Retrospective Data Analysis ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Benign Prostate ◽  
Formalin Fixed

We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients.

Circulating tumor cells (CTC) in metastatic hepatocellular carcinoma (HCC): Comparison to control patients with nonmalignant liver diseases (NMLD) and exploratory characterization by next generation sequencing (NGS).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 207-207
Author(s):  
Robin Katie Kelley ◽  
Mark Jesus Mendoza Magbanua ◽  
Timothy M Butler ◽  
Nikoletta Sidiropoulos ◽  
Jimmy Hwang ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Small Sample ◽  
Peripheral Blood Mononuclear ◽  
Exact Test ◽  
Coverage Bias ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Noninvasive Biomarkers ◽  
Poor Outcomes ◽  
Next Generation Sequencing Ngs

207 Background: Noninvasive biomarkers are urgently needed to improve diagnosis, prognosis, and molecular characterization in HCC. Detection of CTC by EpCAM-enrichment methods is associated with poor outcomes in other tumors. Approximately 35% of HCC are EpCAM+. We hypothesized that CTC are detectable in a subset of metastatic HCC but not in NMLD and that CTC DNA might serve as a source of tumor DNA for biomarker detection and discovery. Methods: Whole blood was obtained from (1) patients with metastatic HCC and (2) NMLD controls. CTC were enumerated using CellSearch by blinded investigators. If > 10 CTC/7.5 mL, immunomagnetic enrichment for EpCAM followed by fluorescence-activated cell sorting (FACS) was also performed to collect highly purified CTC for whole genome amplification (WGA) by GenomePlex WGA4 kit. NGS using 46-gene AmpliSeq Cancer Panel (Ion Torrent) was performed on DNA from CTC, formalin-fixed paraffin embedded tumor (FFPE), and peripheral blood mononuclear cells (PBMC) if available. Results: 20 HCC and 10 NMLD were enrolled. FFPE was available in 7 HCC. In HCC cohort, median alpha-fetoprotein (AFP) was 492 ng/mL (range: 3.8-587,134) and vascular invasion (VI) was present in 13/20 (65%). CTC ≥ 3/7.5 mL were detected in 6/20 (30%, 95% CI: 0.08, 0.52) HCC and 0/9 (95% CI: 0, 0) eligible NMLD (p=0.07). One NMLD had CTC > 3/7.5 mL but was found to have HCC on surveillance ultrasound and excluded. CTC ≥ 3/7.5 mL were associated with AFP ≥ 400 (p=0.01) and VI (p=0.05) by Fisher’s exact test. NGS identified mutations listed in COSMIC in the majority including TP53 and CTNNB1. Variants appeared more frequent in CTC than FFPE in this small sample. Coverage was significantly lower in CTC than FFPE (coverage 20x mean 50% vs 93%, p < 0.02 by unpaired t-test). Conclusions: CTC are a promising biomarker in metastatic HCC and merit further study, including non-EpCAM methods. CTC were associated with AFP and VI. NGS of CTC WGA DNA is feasible and identified characteristic mutations but was limited by coverage bias. Updated NGS findings including 5 cases with paired CTC, FFPE, and/or PBMC will be presented.

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