BCL-2 expression aids in the immunohistochemical prediction of the Oncotype DX breast cancer recurrence score

Zarella, Mark D.; Heintzelman, Rebecca; Popnikolov, Nikolay K.; Garcia, Fernando U.

doi:10.1186/s12907-018-0082-3

Cited by 4 publications

(3 citation statements)

References 62 publications

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“…Although there is a direct relationship between H-score and the more conventional percent positive metric, H-score may have additional prognostic value not wholly captured by percent positivity. [505152]…”

Section: The Basics Of Image Analysismentioning

confidence: 99%

Introduction to Digital Image Analysis in Whole-slide Imaging: A White Paper from the Digital Pathology Association

Aeffner

Zarella

Buchbinder³

et al. 2019

Journal of Pathology Informatics

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288

239

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The advent of whole-slide imaging in digital pathology has brought about the advancement of computer-aided examination of tissue via digital image analysis. Digitized slides can now be easily annotated and analyzed via a variety of algorithms. This study reviews the fundamentals of tissue image analysis and aims to provide pathologists with basic information regarding the features, applications, and general workflow of these new tools. The review gives an overview of the basic categories of software solutions available, potential analysis strategies, technical considerations, and general algorithm readouts. Advantages and limitations of tissue image analysis are discussed, and emerging concepts, such as artificial intelligence and machine learning, are introduced. Finally, examples of how digital image analysis tools are currently being used in diagnostic laboratories, translational research, and drug development are discussed.

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Section: The Basics Of Image Analysismentioning

confidence: 99%

Introduction to Digital Image Analysis in Whole-slide Imaging: A White Paper from the Digital Pathology Association

Aeffner

Zarella

Buchbinder³

et al. 2019

Journal of Pathology Informatics

Self Cite

288

239

View full text Add to dashboard Cite

show abstract

“…A median H-score of 34 for Bcl2 expression in TNBC PDX tumors was considered as a cut-off for analysis. A similar scoring system for Bcl2 has been recently reported by a few other studies [54,55]. Only one out of six CTCcl− TNBC PDX tumors had an H-score of > 34 (BCM-3107 with H-score of 80).…”

Section: Resultsmentioning

confidence: 62%

A CTC-Cluster-Specific Signature Derived from OMICS Analysis of Patient-Derived Xenograft Tumors Predicts Outcomes in Basal-Like Breast Cancer

Thangavel

Angelis

Vasaikar

et al. 2019

JCM

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Circulating tumor cell clusters (CTCcl) have a higher metastatic potential compared to single CTCs and predict long-term outcomes in breast cancer (BC) patients. Because of the rarity of CTCcls, molecular characterization of primary tumors that give rise to CTCcl hold significant promise for better diagnosis and target discovery to combat metastatic BC. In our study, we utilized the reverse-phase protein array (RPPA) and transcriptomic (RNA-Seq) data of 10 triple-negative BC patient-derived xenograft (TNBC PDX) transplantable models with CTCs and evaluated expression of upregulated candidate protein Bcl2 (B-cell lymphoma 2) by immunohistochemistry (IHC). The sample-set consisted of six CTCcl-negative (CTCcl−) and four CTCcl-positive (CTCcl+) models. We analyzed the RPPA and transcriptomic profiles of CTCcl− and CTCcl+ TNBC PDX models. In addition, we derived a CTCcl-specific gene signature for testing if it predicted outcomes using a publicly available dataset from 360 patients with basal-like BC. The RPPA analysis of CTCcl+ vs. CTCcl− TNBC PDX tumors revealed elevated expression of Bcl2 (false discovery rate (FDR) < 0.0001, fold change (FC) = 3.5) and reduced acetyl coenzyme A carboxylase-1 (ACC1) (FDR = 0.0005, FC = 0.3) in CTCcl+ compared to CTCcl− tumors. Genome-wide transcriptomic analysis of CTCcl+ vs. CTCcl− tumors revealed 549 differentially expressed genes associated with the presence of CTCcls. Apoptosis was one of the significantly downregulated pathways (normalized enrichment score (NES) = −1.69; FDR < 0.05) in TNBC PDX tumors associated with CTCcl positivity. Two out of four CTCcl+ TNBC PDX primary tumors had high Bcl2 expression by IHC (H-score > 34); whereas, only one of six CTCcl− TNBC PDX primary tumors met this criterion. Evaluation of epithelial-mesenchymal transition (EMT)-specific signature did not show significant differences between CTCcl+ and CTCcl− tumors. However, a gene signature associated with the presence of CTCcls in TNBC PDX models was associated with worse relapse-free survival in the publicly available dataset from 360 patients with basal-like BC. In summary, we identified the multigene signature of primary PDX tumors associated with the presence of CTCcls. Evaluation of additional TNBC PDX models and patients can further illuminate cellular and molecular pathways facilitating CTCcl formation.

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“…The following method is used to get the final score: [1 (% cells 1+) + 2 (% cells 2+) + 3 (% cells 3+)]. The final score is between 0 and 300 [ 32 ]. Furthermore, tumor cases were divided according to the median of the H-score into low and high expression.…”

Section: Methodsmentioning

confidence: 99%

STIM1/SOX2 proteins are co-expressed in the tumor and microenvironmental stromal cells of pancreatic ductal adenocarcinoma and ampullary carcinoma

Sweed,

Elhamed,

Aiad

et al. 2024

World J Surg Onc

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Pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (AAC) are lethal malignancies with modest benefits from surgery. SOX2 and STIM1 have been linked to anticancer activity in several human malignancies. This study included 94 tumor cases: 48 primary PDAC, 25 metastatic PDAC, and 21 primary AAC with corresponding non-tumor tissue. All cases were immunohistochemically stained for STIM1 and SOX2 and results were correlated with clinicopathologic data, patient survival, and BCL2 immunostaining results. Results revealed that STIM1 and SOX2 epithelial/stromal expressions were significantly higher in PDAC and AAC in comparison to the control groups. STIM1 and SOX2 expressions were positively correlated in the primary and metastatic PDAC (P = 0.016 and, P = 0.001, respectively). However, their expressions were not significantly associated with BCL2 expression. SOX2 epithelial/stromal expressions were positively correlated with the large tumor size in the primary AAC group (P = 0.052, P = 0.044, respectively). STIM1 stromal and SOX2 epithelial over-expressions had a bad prognostic impact on the overall survival of AAC (P = 0.002 and P = 0.001, respectively). Therefore, STIM1 and SOX2 co-expression in tumor cells and intra-tumoral stroma could contribute to the development of PDAC and AAC. STIM1/SOX2 expression is linked to a bad prognosis in AAC.

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BCL-2 expression aids in the immunohistochemical prediction of the Oncotype DX breast cancer recurrence score

Cited by 4 publications

References 62 publications

Introduction to Digital Image Analysis in Whole-slide Imaging: A White Paper from the Digital Pathology Association

Introduction to Digital Image Analysis in Whole-slide Imaging: A White Paper from the Digital Pathology Association

A CTC-Cluster-Specific Signature Derived from OMICS Analysis of Patient-Derived Xenograft Tumors Predicts Outcomes in Basal-Like Breast Cancer

STIM1/SOX2 proteins are co-expressed in the tumor and microenvironmental stromal cells of pancreatic ductal adenocarcinoma and ampullary carcinoma

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