scholarly journals Breast tall cell carcinoma with reversed polarity with an unusual molecular profile

2020 ◽  
Vol 7 (1) ◽  
pp. 46
Author(s):  
Kaitlyn J Nielson ◽  
Edgar G. Fischer ◽  
Jacklyn Jacklyn Nemunaitis ◽  
Sangeetha Prabhakaran ◽  
Nadja K. Falk
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Molecular Analysis ◽  
Molecular Profile ◽  
Published Data ◽  
Low Grade ◽  
Tall Cell ◽  
Reversed Polarity

Breast tall cell carcinoma with reversed polarity (TCCRP) is rare and previously referred to as solid papillary carcinoma with reverse polarity.  This low grade tumor commonly exhibits IDH2 p.Arg172 mutation, however is not completely understood at the molecular level.  We present a case of TCCRP in a 55 year old woman with a 0.7 cm left breast mass.  A core biopsy was performed with immunohistochemistry.  Lumpectomy and sentinel lymph node biopsy were completed two months later.  MammaPrint$^{\textregistered}$ and BluePrint$^{\textregistered}$ gene expression profilers were performed on an excision block.  Microscopically, the tumor was composed of circumscribed nests of columnar cells, with focal papillary architecture.  Tumor cells had apically located nuclei with grooves and rare inclusions. Tumor cells were positive for CK5, IDH1/2, and calretinin, and myoepithelial cells were absent.  BluePrint$^{\textregistered}$ subtyped the tumor as basaloid.  MammaPrint$^{\textregistered}$ classified the tumor as high risk for metastasis.  TCCRP presents a diagnostic challenge.  Although these rare breast carcinomas are generally reported to have an indolent clinical course, molecular analysis by gene expression profiling classified this tumor as high risk of recurrence with a basaloid type.  Therefore, molecular analysis of this tumor may lead to conflicting data regarding prognosis and treatment considerations.  Clinicians and patients should weigh published data and individual prognostic information for treatment planning.  Our patient and clinical team opted for radiation without chemotherapy.  More cases of TCCRP need to be studied to better understand its molecular profile.

Tall cell carcinoma with reversed polarity: A case report of a very rare breast tumor entity and mini‐review

2021 ◽  
Vol 27 (4) ◽  
pp. 369-376
Author(s):  
Helen J. Trihia ◽  
Pavlos Lampropoulos ◽  
Loukas Karelis ◽  
Efthymia Souka ◽  
Georgios Galanopoulos ◽  
...  
Keyword(s):  
Case Report ◽  
Cell Carcinoma ◽  
Breast Tumor ◽  
Tall Cell ◽  
Tumor Entity ◽  
Reversed Polarity

Integrated Transcriptomic Analysis of Necrosis-related Gene in Diffuse Gliomas

2019 ◽  
Vol 80 (04) ◽  
pp. 240-249
Author(s):  
Jiajia Wang ◽  
Jie Ma
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Prognostic Index ◽  
Gene Expression Profiles ◽  
Risk Groups ◽  
Low Risk ◽  
Differentially Expressed ◽  
Low Grade

Glioblastoma multiforme (GBM), an aggressive brain tumor, is characterized histologically by the presence of a necrotic center surrounded by so-called pseudopalisading cells. Pseudopalisading necrosis has long been used as a prognostic feature. However, the underlying molecular mechanism regulating the progression of GBMs remains unclear. We hypothesized that the gene expression profiles of individual cancers, specifically necrosis-related genes, would provide objective information that would allow for the creation of a prognostic index. Gene expression profiles of necrotic and nonnecrotic areas were obtained from the Ivy Glioblastoma Atlas Project (IVY GAP) database to explore the differentially expressed genes.A robust signature of seven genes was identified as a predictor for glioblastoma and low-grade glioma (GBM/LGG) in patients from The Cancer Genome Atlas (TCGA) cohort. This set of genes was able to stratify GBM/LGG and GBM patients into high-risk and low-risk groups in the training set as well as the validation set. The TCGA, Repository for Molecular Brain Neoplasia Data (Rembrandt), and GSE16011 databases were then used to validate the expression level of these seven genes in GBMs and LGGs. Finally, the differentially expressed genes (DEGs) in the high-risk and low-risk groups were subjected to gene ontology enrichment, Kyoto Encyclopedia of Genes and Genomes pathway, and gene set enrichment analyses, and they revealed that these DEGs were associated with immune and inflammatory responses. In conclusion, our study identified a novel seven-gene signature that may guide the prognostic prediction and development of therapeutic applications.

Gene expression profiling identifies two distinct papillary renal cell carcinoma (RCC) subgroups of contrasting prognosis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4503-4503
Author(s):  
B. T. Teh ◽  
X. J. Yang ◽  
M. Tan ◽  
H. L. Kim ◽  
W. Stadler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Comparative Genomic ◽  
Low Grade ◽  
Class 1

4503 Background: Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphological classification of PRCC into Type 1 and Type 2 tumors has been recently proposed, but its biological relevance remains uncertain. Methods: We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analysis. Comparative genomic microarray analysis (CGMA) was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples, with 15 independent tumors. Results: We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histological subtypes: Type 1, low-grade Type 2 and mixed Type 1/low-grade Type 2 tumors. The second class, with poor survival, corresponded to high-grade Type 2 tumors (n = 11). Dysregulation of G1/S and G2/M checkpoint genes were found in Class 1 and Class 2 tumors respectively, alongside characteristic chromosomal aberrations. We identified a 7-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in Class 1 tumors, and of topoisomerase IIα in Class 2 tumors. Conclusions: We report two molecular subclasses of PRCC, which are biologically and clinically distinct, which may be readily distinguished in a clinical setting. This may also have therapeutic implications. No significant financial relationships to disclose.

Analysis of molecular profiling of renal cell carcinoma: Identification of a 4-microRNA signature as a prognostic value in patients with stage I-II disease.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 395-395 ◽  
Author(s):  
Daniel E. Castellano ◽  
Carlos A. Farfán ◽  
Gamez Angelo ◽  
Juan M. Sepúlveda ◽  
Guillermo De Velasco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Mirna Expression ◽  
Renal Cell ◽  
Recurrence Risk ◽  
Stage I ◽  
Risk Of Relapse ◽  
Mirna Expression Signature

395 Background: Renal-cell carcinoma (RCC) accounts for 3% of all cancers and produces over 12,000 deaths every year in the EE.UU. Currently, there is a need to identify stage I/II RCC patients with high risk of relapse following nephrectomy, given that these patients do not receive adjuvant treatment and ≈ 25% of them relapse. MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNA and playing an important role as regulators of gene expression during tumorigenesis. Our willing is to define a miRNA expression profile associated with a high risk of relapse in early RCC. Methods: We analyzed 113 pts. with RCC stage I-II of a local data-base who had undergone nephrectomy from 2000 to 2008. RNA was extracted from FFPE samples using RecoverAll (Ambion). RNA samples were hybridized to Human miRNA Microarray Release 14.0, 8x15K (Agilent Technologies. Data were normalized using Quantile Normalization. Only 396 miRNAs with detectable signal in at least 10% of the hybridized samples were considered for further analysis. Identification of miRNAs related with recurrence risk and subsequent developing and validation of miRNA expression-based prediction models of recurrence risk were performed in BRB-ArrayTools v4.2.1. Results: We identified a 4-miRNA expression signature that distinguishes early stage RCC patients with low and high recurrence risk (p value = 0.0013; HR = 4.68 [1.82-12.0]). Distant recurrence free survival rate at five years was 97.4 and 81.2 for the low and high recurrence risk groups respectively. High levels of miR-424 were related with a high recurrence risk (p = 0.023). Conclusions: The TNM staging system lacks accuracy to identify prognostic markers of survival in early RCC. Our results suggest that specific miRNAs are involved in the recurrence of early disease. We have found a miRNA expression signature that identifies patients with high risk of developing distant metastasis using the FFPE sample of primary tumors. High expression levels of miR-424 were related with a high recurrence risk. MiR-424 is a hypoxia induced miRNA whose expression has been related with HIF-1α and HIF-2α stabilization and angiogenesis induction.

scholarly journals Analytical validity of DecisionDx-SCC, a gene expression profile test to identify risk of metastasis in cutaneous squamous cell carcinoma (SCC) patients

2021 ◽  
Author(s):  
Sherri Borman ◽  
Jeff Wilkinson ◽  
Lauren Meldi-Sholl ◽  
Clare Johnson ◽  
Kelsey Carter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Risk Class ◽  
Class 1

Abstract Background To improve identification of patients with cutaneous squamous cell carcinoma (SCC) at high risk for metastatic disease, the DecisionDx-SCC assay, a prognostic 40-gene expression profile (40-GEP) test, was developed and validated. The 40-GEP assay utilizes RT-PCR gene expression analysis on primary tumor biopsy tissue to evaluate the expression of 34 signature gene targets and 6 normalization genes. The test provides classifications of low risk (Class 1), moderate risk (Class 2A), and high risk (Class 2B) of metastasis within 3 years of diagnosis. The primary objective of this study was to validate the analytical performance of the 40 gene expression signature. Methods The repeatability and reproducibility of the 40-GEP test was evaluated by performance of inter-assay, intra-assay, and inter-operator precision experiments along with monitoring the reliability of sample and reagent stability for class call concordance. The technical performance of clinical orders from September 2020 through July 2021 for the 40-GEP test was assessed. Results Patient hematoxylin and eosin (H&E) stained slides were reviewed by a board-certified pathologist to assess minimum acceptable tumor content. Class specific controls (Class 1 and Class 2B) were evaluated with Levey Jennings analysis and demonstrated consistent and reproducible results. Inter-assay, inter-operator and intra-assay concordance were all ≥90%, with short-term and long-term RNA stability also meeting minimum concordance requirements. Of the 2,446 orders received, 93.4% remained eligible for testing, with 96.8% of all tested samples that completed the assay demonstrating actionable class call results. Conclusion DecisionDx-SCC demonstrates a high degree of analytical precision, yielding high concordance rates across multiple performance experiments, along with exhibiting robust technical reliability on clinical samples.

scholarly journals Histologically resolved spatial multi-omics of human oral squamous cell carcinoma

2017 ◽  
Author(s):  
Tao Chen ◽  
Chen Cao ◽  
Jianyun Zhang ◽  
Aaron Streets ◽  
Yanyi Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Spatial Resolution ◽  
Squamous Cell ◽  
Single Cells ◽  
Expression Patterns ◽  
Critical Role ◽  
Molecular Profile ◽  
Tissue Samples

AbstractBoth the composition of cell types and their spatial distribution in a tissue play a critical role in cellular function, organ development, and disease progression. For example, intratumor heterogeneity and the distribution of transcriptional and genetic events in single cells drive the genesis and development of cancer. However, it can be challenging to fully characterize the molecular profile of cells in a tissue with high spatial resolution because microscopy has limited ability to extract comprehensive genomic information, and the spatial resolution of genomic techniques tends to be limited by dissection. There is a growing need for tools that can be used to explore the relationship between histological features, gene expression patterns, and spatially correlated genomic alterations in healthy and diseased tissue samples. Here, we present a technique that combines label-free histology with spatially resolved multi-omics in un-fixed and unstained tissue sections. This approach leverages stimulated Raman scattering microscopy to provide chemical contrast that reveals histological tissue architecture, allowing for high-resolution in situ laser micro-dissection of regions of interests. These micro-tissue samples are then processed for DNA and RNA sequencing to identify unique genetic profiles that correspond to distinct anatomical regions. We demonstrate the capabilities of this technique by mapping gene expression and copy number alterations to histologically defined regions in human squamous cell carcinoma (OSCC). Our approach provides complementary insights in tumorigenesis and offers an integrative tool for macroscale cancer tissues with spatial multi-omics assessments.

Sign in / Sign up

Export Citation Format

Share Document