<i><scp>HER</scp>2</i><scp>FISH</scp>results in breast cancers with increased<scp>CEN</scp>17 signals using alternative chromosome 17 probes – reclassifying cases in the equivocal category

Holzschuh, M.; Czyż, Zbigniew T.; Hauke, Sven; Inwald, Elisabeth C.; Polzer, Bernhard; Brockhoff, Gero

doi:10.1111/his.13253

Cited by 13 publications

(9 citation statements)

References 37 publications

(89 reference statements)

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“…FISH on tumor tissue samples of the GeparTrio cohort was applied to tissue microarrays generated by the Institute of Pathology (Philipps‐University Marburg). A ZytoLight SPEC MDM2/CEN12 dual color probe (ZytoVision GmbH, Bremerhaven, Germany) was used as previously described and samples from excised from HTM were done analogously 24 . More details are given in the Supporting Information Material.…”

Section: Methodsmentioning

confidence: 99%

mdm2 gene amplification is associated with luminal breast cancer progression in humanized PDX mice and a worse outcome of estrogen receptor positive disease

Wege

Rom-Jurek

Jank

et al. 2021

Intl Journal of Cancer

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Estrogen receptor‐positive breast cancer is a highly prevalent but heterogeneous disease among women. Advanced molecular stratification is required to enable individually most efficient treatments based on relevant prognostic and predictive biomarkers. First objective of our study was the hypothesis‐driven discovery of biomarkers involved in tumor progression upon xenotransplantation of Luminal breast cancer into humanized mice. The second objective was the marker validation and correlation with the clinical outcome of Luminal breast cancer disease within the GeparTrio trial. An elevated mdm2 gene copy number was associated with enhanced tumor growth and lung metastasis in humanized tumor mice. The viability, proliferation and migration capacity of inherently mdm2 positive breast cancer cells in vitro were significantly reduced upon mdm2 knockdown or anti‐mdm2 targeting. An mdm2 gain significantly correlated with a worse DFS and OS of Luminal breast cancer patients, albeit it was also associated with an enhanced preoperative pathological response rate. We provide evidence for an enhanced Luminal breast cancer stratification based on mdm2. Moreover, mdm2 can potentially be utilized as a therapeutic target in the Luminal subtype.

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Section: Methodsmentioning

confidence: 99%

mdm2 gene amplification is associated with luminal breast cancer progression in humanized PDX mice and a worse outcome of estrogen receptor positive disease

Wege

Rom-Jurek

Jank

et al. 2021

Intl Journal of Cancer

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“…Tissue microarrays (TMAs) were generated as described previously [ 45 ] and were used for PD-L1 immunohistochemistry and PD-L1/cen9 FISH analyses. In brief, for each tumor a representative tumor section was selected from a hematoxylin and eosin (H&E)-stained section of the donor block.…”

Section: Methodsmentioning

confidence: 99%

The presence of PD-1 positive tumor infiltrating lymphocytes in triple negative breast cancers is associated with a favorable outcome of disease

et al. 2017

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Triple negative breast cancer patients have a poor course of disease not least because of limited treatment options however immunotherapy by targeting the PD-1/PD-L1 checkpoint system is a promising strategy to improve the outcome. Here we systematically investigated the expression of PD-1 on tumor infiltrating lymphocytes and PD-L1 on both tumor and infiltrated immune cells. Moreover, the PD-L1 gene status in tumor cells was assessed.103 tissue microarray samples derived from triple negative breast cancer specimens were immunohistochemically stained against PD-1 and PD-L1. Dual marker fluorescence in-situ hybridization was applied to the PD-L1 gene and centromere region of chromosome 9. The disease free and overall survival rates were determined as a function of the PD-1/PD-L1 status.A slight gain of the PD-L1 gene region was found in 55% of all samples but an elevated PD-L1/cen9 ratio was rather rare (7%). An increased gene dose is not associated with an enhanced protein expression and the PD-L1 expression only weakly correlates with the amount of immune cell infiltration. Instead, we found an association of PD-L1 expression on tumor and immune cells, respectively. Notably, the PD-1 expression on immune cells is associated with a favorable disease free and overall survival. PD-1 expression indicates an enhanced immunological anti-tumor activity and represents a favorable prognostic impact. A deeper understanding of factors that affect the regulation and function of the PD-1/PD-L1 system is required to establish predictive variables and to utilize the system for therapeutic intervention of triple negative breast cancer patients.

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“…[3][4][5][6] An increased CEP17 copy number substantially more often represents a focal pericentromeric gain or so-called "co-amplification" of the centromeric region of chromosome 17. [3][4][5][6] Although the ASCO/CAP guidelines on HER2 testing do not provide a definition for CEP17 amplification, 1 most studies define CEP17 amplification as a mean CEP17 copy number of ≥3.0 copies. 4,7 The prevalence of isolated CEP17 copy number amplification has not yet been extensively studied, and little is known about its clinical significance.…”

Section: Images In Pathologymentioning

confidence: 99%

Isolated CEP17 Copy Number Gain in Invasive Breast Cancer Results in a “Reverse” Amplification Status

Bockstal

Dubois

Talpe³

et al. 2020

Int J Surg Pathol

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HER2FISHresults in breast cancers with increasedCEN17 signals using alternative chromosome 17 probes – reclassifying cases in the equivocal category

Cited by 13 publications

References 37 publications

mdm2 gene amplification is associated with luminal breast cancer progression in humanized PDX mice and a worse outcome of estrogen receptor positive disease

mdm2 gene amplification is associated with luminal breast cancer progression in humanized PDX mice and a worse outcome of estrogen receptor positive disease

The presence of PD-1 positive tumor infiltrating lymphocytes in triple negative breast cancers is associated with a favorable outcome of disease

Isolated CEP17 Copy Number Gain in Invasive Breast Cancer Results in a “Reverse” Amplification Status

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