Abstract P210: MDM2 gene amplification as a predictive biomarker for the MDM2 inhibitor milademetan

Author(s):  
Vijaya G. Tirunagaru ◽  
Mrinal M. Gounder ◽  
Prasanna R. Kumar ◽  
David S. Hong ◽  
Robert C. Doebele
2020 ◽  
Vol 28 (7) ◽  
pp. 749-758
Author(s):  
Muhammad Usman Tariq ◽  
Naila Kayani ◽  
Tariq Moatter ◽  
Nasir Ud Din

Background. Diagnosis of dedifferentiated liposarcoma (DDL) can sometimes be challenging due to a wide variety of histological features. “Meningothelial-like” whorl is an uncommon histological feature of DDL, which is also observed in neural tumors and follicular dendritic cell sarcoma. This feature is frequently associated with metaplastic bone formation. We conducted this study to describe the clinicopathological features of DDL with meningothelial-like whorls that would aid in establishing accurate diagnosis. Material and Methods. Microscopic glass slides of 5 cases of DDL with meningothelial-like whorls, diagnosed between January 2010 and December 2019, were reviewed. Results. Paratesticular region was the most common site. Whorls occupied 10% to 75% of tumor area and ranged in size from <0.1 cm to >2 cm. In 1 case, these whorls coalesced to form large areas of dedifferentiation. The cells forming whorls were spindle to epithelioid shaped and lacked significant nuclear pleomorphism and increased mitoses. Metaplastic bone formation was observed in 4 cases and cartilage formation in 3 cases. p16 and α-smooth muscle actin (α-SMA) immunohistochemical stains were positive in 2 cases, when performed. MDM2 gene amplification was observed in all cases by fluorescence in situ hybridization technique. These tumors showed aggressive behavior, similar to that of DDL without meningothelial-like whorls. Two patients died, 1 developed recurrence, 1 presented as recurrent tumor, and 1 developed metastasis. Conclusion. Meningothelial-like whorls in DDL most likely represent an early stage of dedifferentiation. Presence of well-differentiated liposarcoma areas, metaplastic bone formation, positive expressions for p16 and α-SMA immunohistochemical stains, and MDM2 gene amplification are useful diagnostic clues. These tumors have the potential to behave aggressively.


Lung Cancer ◽  
2005 ◽  
Vol 49 ◽  
pp. S122-S123
Author(s):  
D. Dworakowska ◽  
E. Jassem ◽  
J. Jassem ◽  
R. Schneider-Stock ◽  
C. Boltze ◽  
...  

2000 ◽  
Vol 13 (6) ◽  
pp. 621-626 ◽  
Author(s):  
Thomas Günther ◽  
Regine Schneider-Stock ◽  
Carsten Häckel ◽  
Hans-Udo Kasper ◽  
Matthias Pross ◽  
...  

2021 ◽  
Author(s):  
Rintaro Noro ◽  
Kazufumi Honda ◽  
Kengo Nagashima ◽  
Noriko Motoi ◽  
Shinobu Kunugi ◽  
...  

2020 ◽  
Vol 66 (10) ◽  
pp. 483-490
Author(s):  
Yoshihisa MORISHITA ◽  
Shintaro SUZUKI ◽  
Hiroki GOTO ◽  
Masahiro FUKUMURA ◽  
Satoru MIYABE ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3632-3632
Author(s):  
Akram Mesleh Shayeb ◽  
Razelle Kurzrock ◽  
Shumei Kato

3632 Background: HER2 alterations is a predictive biomarker for anti-HER2 regimen. Success in breast and gastric cancers with anti-HER2 therapies translated to explore their efficacy in other tumors. Currently, measurement of HER2 can be done by assessing the expression of protein [e.g. immunohistochemistry (IHC)] or gene amplification of copy number variation (CNV) [e.g. fluorescence in situ hybridization or next-generation sequencing (NGS)]. But little is known about the transcription level (mRNA) of HER2. Herein, we investigated HER2 mRNA expression and its association with gene and protein expressions among diverse cancer types. Methods: Between 2015-2019, HER2 status was evaluated using IHC, qRT-PCR and NGS by Paradigm Diagnostics (CLIA-certified laboratory). All tumors in the database were included for analysis. Correlations between all 3 tests were done. An illustrative patient who was treated with anti-HER2 therapy base on the mRNA testing is presented. Results: HER2 testing was performed on 5305 patients (pts) with diverse cancers including NSCLC (n=1175), breast (n=1040) and colon (n=566); 4.1% (161/3926) had amplification through NGS, 33.3% (615/1848) had mRNA overexpression and 9.3% (236/2533) had overexpression by IHC. Of 723 pts who had all three tests performed, we found 7.5% (54/723) of pts with all three HER2 markers being positive (CNV [+]/mRNA [+]/ IHC [+]). Meanwhile, variety of amplification/ expression patterns were seen (see Table). CNV positivity translated to protein expression in 95% of cases. While only 4% of pts were IHC positive when CNV and mRNA were negative. 20% (144/723) of pts had mRNA overexpression alone among diverse cancer types. Representative case of 70yo female with metastatic cholangiocarcinoma harboring mRNA overexpression (but negative for CNV, IHC unclear due to sample insufficiency) who had near complete response to anti-HER2 therapy with progression-free survival of 24+ months is presented. Conclusions: HER2 status can be discordant with different assays but NGS positivity has excellent correlation with mRNA and protein expression. Of importance, HER2 mRNA can be overexpressed in 20% of pts even when gene amplification and protein expression are negative. Further studies are warranted to determine the clinical utility of mRNA as a biomarker for HER2 and potential use for anti-HER2 targeted therapies. [Table: see text]


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