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Article ; Online: Lessons from genomic profiling: towards a molecular-based classification of ovarian Sertoli-Leydig cell tumour.

Kommoss, Felix K F

2023 Volume 84, Issue 4, Page(s) 712–714

Abstract: Currently available molecular data support a dichotomous classification of Sertoli-Leydig cell tumours (SLCTs) based on DICER1 mutational status. This correspondence suggests a possible roadmap towards a molecular-based classification of SLCT. ...

Abstract	Currently available molecular data support a dichotomous classification of Sertoli-Leydig cell tumours (SLCTs) based on DICER1 mutational status. This correspondence suggests a possible roadmap towards a molecular-based classification of SLCT.
MeSH term(s)	Male ; Female ; Humans ; Sertoli-Leydig Cell Tumor/genetics ; Sertoli-Leydig Cell Tumor/pathology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Sex Cord-Gonadal Stromal Tumors/pathology ; Ribonuclease III/genetics ; Genomics ; DEAD-box RNA Helicases/genetics
Chemical Substances	Ribonuclease III (EC 3.1.26.3) ; DICER1 protein, human (EC 3.1.26.3) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2023-12-19
Publishing country	England
Document type	Letter
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.15110
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Article ; Online: Small-cell carcinoma of the ovary hypercalcaemic type shows a wild-type immunohistochemical staining pattern of p53.

Kommoss, Felix K F / Schmidt, Dietmar / Kommoss, Friedrich / Tessier-Cloutier, Basile

Histopathology

2023 Volume 83, Issue 1, Page(s) 154–156

MeSH term(s)	Female ; Humans ; Tumor Suppressor Protein p53 ; Ovary/pathology ; Carcinoma, Small Cell/pathology ; Small Cell Lung Carcinoma ; Lung Neoplasms
Chemical Substances	Tumor Suppressor Protein p53
Language	English
Publishing date	2023-04-17
Publishing country	England
Document type	Letter
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.14926
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Article ; Online: p53 Immunohistochemical Staining and TP53 Gene Mutations in Endometrial Cancer: Does Null Pattern Correlate With Prognosis?

Kommoss, Felix K F / Jamieson, Amy / McAlpine, Jessica N / Gilks, C Blake

The American journal of surgical pathology

2023 Volume 48, Issue 3, Page(s) 373

MeSH term(s)	Female ; Humans ; Tumor Suppressor Protein p53/genetics ; Genes, p53 ; Mutation ; Prognosis ; Endometrial Neoplasms/genetics
Chemical Substances	Tumor Suppressor Protein p53 ; TP53 protein, human
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	752964-8
ISSN	1532-0979 ; 0147-5185
ISSN (online)	1532-0979
ISSN	0147-5185
DOI	10.1097/PAS.0000000000002170
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Article: Preclinical In Vivo Modeling of Pediatric Sarcoma-Promises and Limitations.

Imle, Roland / Kommoss, Felix K F / Banito, Ana

Journal of clinical medicine

2021 Volume 10, Issue 8

Abstract: Pediatric sarcomas are an extremely heterogeneous group of genetically distinct diseases. Despite the increasing knowledge on their molecular makeup in recent years, true therapeutic advancements are largely lacking and prognosis often remains dim, ... ...

Abstract	Pediatric sarcomas are an extremely heterogeneous group of genetically distinct diseases. Despite the increasing knowledge on their molecular makeup in recent years, true therapeutic advancements are largely lacking and prognosis often remains dim, particularly for relapsed and metastasized patients. Since this is largely due to the lack of suitable model systems as a prerequisite to develop and assess novel therapeutics, we here review the available approaches to model sarcoma in vivo. We focused on genetically engineered and patient-derived mouse models, compared strengths and weaknesses, and finally explored possibilities and limitations to utilize these models to advance both biological understanding as well as clinical diagnosis and therapy.
Language	English
Publishing date	2021-04-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10081578
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Article ; Online: Improved preoperative risk stratification in endometrial carcinoma patients: external validation of the ENDORISK Bayesian network model in a large population-based case series.

Grube, Marcel / Reijnen, Casper / Lucas, Peter J F / Kommoss, Frieder / Kommoss, Felix K F / Brucker, Sara Y / Walter, Christina B / Oberlechner, Ernst / Krämer, Bernhard / Andress, Jürgen / Neis, Felix / Staebler, Annette / Pijnenborg, Johanna M A / Kommoss, Stefan

Journal of cancer research and clinical oncology

2022 Volume 149, Issue 7, Page(s) 3361–3369

Abstract: Purpose: Preoperative risk stratification of newly diagnosed endometrial carcinoma (EC) patients has been hindered by only moderate prediction performance for many years. Recently ENDORISK, a Bayesian network model, showed high predictive performance. ... ...

Abstract	Purpose: Preoperative risk stratification of newly diagnosed endometrial carcinoma (EC) patients has been hindered by only moderate prediction performance for many years. Recently ENDORISK, a Bayesian network model, showed high predictive performance. It was the aim of this study to validate ENDORISK by applying the model to a population-based case series of EC patients. Methods: ENDORISK was applied to a retrospective cohort of women surgically treated for EC from 2003 to 2013. Prediction accuracy for LNM as well as 5-year DSS was investigated. The model's overall performance was quantified by the Brier score, discriminative performance by area under the curve (AUC). Results: A complete dataset was evaluable from 247 patients. 78.1% cases were endometrioid histotype. The majority of patients (n = 156;63.2%) had stage IA disease. Overall, positive lymph nodes were found in 20 (8.1%) patients. Using ENDORISK predicted probabilities, most (n = 156;63.2%) patients have been assigned to low or very low risk group with a false-negative rate of 0.6%. AUC for LNM prediction was 0.851 [95% confidence interval (CI) 0.761-0.941] with a Brier score of 0.06. For 5-year DSS the AUC was 0.698 (95% CI 0.595-0.800) as Brier score has been calculated 0.09. Conclusions: We were able to successfully validate ENDORISK for prediction of LNM and 5-year DSS. Next steps will now have to focus on ENDORISK performance in daily clinical practice. In addition, incorporating TCGA-derived molecular subtypes will be of key importance for future extended use. This study may support further promoting of data-based decision-making tools for personalized treatment of EC.
MeSH term(s)	Humans ; Female ; Prognosis ; Retrospective Studies ; Bayes Theorem ; Endometrial Neoplasms/pathology ; Risk Assessment ; Lymph Nodes/pathology
Language	English
Publishing date	2022-08-08
Publishing country	Germany
Document type	Journal Article
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-022-04218-4
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Article ; Online: Preclinical In Vivo Modeling of Pediatric Sarcoma—Promises and Limitations

Roland Imle / Felix K. F. Kommoss / Ana Banito

Journal of Clinical Medicine, Vol 10, Iss 1578, p

2021 Volume 1578

Abstract	Pediatric sarcomas are an extremely heterogeneous group of genetically distinct diseases. Despite the increasing knowledge on their molecular makeup in recent years, true therapeutic advancements are largely lacking and prognosis often remains dim, particularly for relapsed and metastasized patients. Since this is largely due to the lack of suitable model systems as a prerequisite to develop and assess novel therapeutics, we here review the available approaches to model sarcoma in vivo. We focused on genetically engineered and patient-derived mouse models, compared strengths and weaknesses, and finally explored possibilities and limitations to utilize these models to advance both biological understanding as well as clinical diagnosis and therapy.
Keywords	pediatric sarcoma ; animal models ; GEMMs ; PDXs ; preclinical testing ; Medicine ; R
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Spindle Cell Sarcoma of the Uterine Corpus With Adipose Metaplasia: Expanding the Morphologic Spectrum of Neoplasms With MEIS1-NCOA2 Gene Fusion.

Kommoss, Felix K F / Kölsche, Christian / Mentzel, Thomas / Schmidt, Dietmar / von Deimling, Andreas / McCluggage, W Glenn / Kommoss, Friedrich

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists

2021 Volume 41, Issue 4, Page(s) 417–422

Abstract: We report a spindle cell sarcoma arising in the uterine corpus of a 26-yr-old patient. The patient underwent a simple hysterectomy and the uterine corpus contained a 9 cm tumor showing nodular and "finger-like" myometrial invasion. Histologically, the ... ...

Abstract	We report a spindle cell sarcoma arising in the uterine corpus of a 26-yr-old patient. The patient underwent a simple hysterectomy and the uterine corpus contained a 9 cm tumor showing nodular and "finger-like" myometrial invasion. Histologically, the tumor was composed of a monomorphic population of atypical spindle cells which contained widespread foci of cytologically benign adipocytes. Immunohistochemistry revealed diffuse strong positivity for CD10, CD56, and CD99 and diffuse weak positive staining with ER and WT1 while smooth muscle markers, S100, TLE1, and cyclin D1 were negative. Total RNA sequencing identified an in-frame fusion between exon 6 of MEIS1 and exon 12 of NCOA2. Copy number analysis revealed few aberrations with no deletions or amplifications identified. No adjuvant therapy was given and the patient is disease-free 9 yr after initial diagnosis. This case represents the second report of a uterine sarcoma harboring a MEIS1-NCOA2/1 gene fusion and expands the morphologic spectrum of recently reported spindle cell sarcomas arising in the genitourinary tract harboring MEIS1-NCOA2/1 gene fusions. This is the first reported case of such tumors with an adipocytic component.
MeSH term(s)	Adult ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Female ; Gene Fusion ; Humans ; Immunohistochemistry ; Metaplasia ; Myeloid Ecotropic Viral Integration Site 1 Protein/genetics ; Nuclear Receptor Coactivator 2/genetics ; Sarcoma/genetics ; Sarcoma/pathology ; Soft Tissue Neoplasms/pathology ; Uterine Neoplasms/genetics
Chemical Substances	Biomarkers, Tumor ; Myeloid Ecotropic Viral Integration Site 1 Protein ; NCOA2 protein, human ; Nuclear Receptor Coactivator 2
Language	English
Publishing date	2021-06-23
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	604859-6
ISSN	1538-7151 ; 0277-1691
ISSN (online)	1538-7151
ISSN	0277-1691
DOI	10.1097/PGP.0000000000000803
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Article ; Online: Genomic characterization of DICER1-associated neoplasms uncovers molecular classes.

Nature communications

2023 Volume 14, Issue 1, Page(s) 1677

Abstract: DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, ... ...

Abstract	DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated "low-grade mesenchymal tumor with DICER1 alteration" (LGMT DICER1), "sarcoma with DICER1 alteration" (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.
MeSH term(s)	Child ; Adolescent ; Humans ; Germ-Line Mutation ; Sarcoma/genetics ; Neoplastic Syndromes, Hereditary/genetics ; Genomics ; Ribonuclease III/genetics ; Genetic Predisposition to Disease ; Rare Diseases ; Mutation ; DEAD-box RNA Helicases/genetics
Chemical Substances	Ribonuclease III (EC 3.1.26.3) ; DICER1 protein, human (EC 3.1.26.3) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2023-03-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-37092-w
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Article ; Online: Teratoma-associated and so-called pure Wilms tumour of the ovary represent two separate tumour types with distinct molecular features.

Kommoss, Felix K F / Chong, Anne-Sophie / Apellaniz-Ruiz, Maria / Turashvili, Gulisa / Park, Kay J / Hanley, Krisztina / Valera, Elvis Terci / von Deimling, Andreas / Vujanic, Gordan / McCluggage, W Glenn / Foulkes, William D

Histopathology

2023 Volume 84, Issue 4, Page(s) 683–696

Abstract: Aims: Ovarian Wilms tumour (WT)/nephroblastoma is an extremely rare neoplasm that has been reported to occur in pure form or as a component of a teratomatous neoplasm. We hypothesized that teratoma-associated and pure ovarian WT may represent different ... ...

Abstract	Aims: Ovarian Wilms tumour (WT)/nephroblastoma is an extremely rare neoplasm that has been reported to occur in pure form or as a component of a teratomatous neoplasm. We hypothesized that teratoma-associated and pure ovarian WT may represent different tumour types with diverging molecular backgrounds. To test this hypothesis, we comprehensively characterized a series of five tumours originally diagnosed as ovarian WT. Methods and results: The five cases comprised three teratoma-associated (two mature and one immature) and two pure WTs. Two of the teratoma-associated WTs consisted of small nodular arrangements of "glandular"/epithelial structures, while the third consisted of both an epithelial and a diffuse spindle cell/blastemal component. The pure WTs consisted of "glandular" structures, which were positive for sex cord markers (including inhibin and SF1) together with a rhabdomyosarcomatous component. The two pure WTs harboured DICER1 pathogenic variants (PVs), while the three associated with teratomas were DICER1 wildtype. Panel-based DNA sequencing of four of the cases did not identify PVs in the other genes investigated. Analysis of the HA19/IGF2 imprinting region showed retention of imprinting in the pure WTs but loss of heterozygosity with hypomethylation of the ICR1 region in two of three teratoma-associated WTs. Furthermore, copy number variation and clustering-based whole-genome DNA methylation analyses identified divergent molecular profiles for pure and teratoma-associated WTs. Conclusion: Based on the morphological features, immunophenotype, and molecular findings (DICER1 PVs, copy number, and DNA methylation profiles), we suggest that the two cases diagnosed as pure primary ovarian WT represent moderately to poorly differentiated Sertoli Leydig cell tumours (SLCTs), while the tumours arising in teratomas represent true WTs. It is possible that at least some prior cases reported as pure primary ovarian WT represent SLCTs.
MeSH term(s)	Male ; Female ; Humans ; DNA Copy Number Variations ; Wilms Tumor/genetics ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Teratoma/genetics ; Teratoma/pathology ; Sex Cord-Gonadal Stromal Tumors ; Kidney Neoplasms/genetics ; Ribonuclease III/genetics ; DEAD-box RNA Helicases/genetics
Chemical Substances	DICER1 protein, human (EC 3.1.26.3) ; Ribonuclease III (EC 3.1.26.3) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2023-12-12
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.15116
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Article ; Online: Dedifferentiated and Undifferentiated Ovarian Carcinoma: An Aggressive and Molecularly Distinct Ovarian Tumor Characterized by Frequent SWI/SNF Complex Inactivation.

Tessier-Cloutier, Basile / Kommoss, Felix K F / Kolin, David L / Němejcová, Kristýna / Smith, DuPreez / Pors, Jennifer / Stewart, Colin J R / McCluggage, W Glenn / Foulkes, William D / von Deimling, Andreas / Köbel, Martin / Lee, Cheng-Han

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2023 Volume 37, Issue 1, Page(s) 100374

Abstract: Dedifferentiated and undifferentiated ovarian carcinomas (DDOC/UDOC) are rare neoplasms defined by the presence of an undifferentiated carcinoma. In this study, we detailed the clinical, pathological, immunohistochemical, and molecular features of a ... ...

Abstract	Dedifferentiated and undifferentiated ovarian carcinomas (DDOC/UDOC) are rare neoplasms defined by the presence of an undifferentiated carcinoma. In this study, we detailed the clinical, pathological, immunohistochemical, and molecular features of a series of DDOC/UDOC. We collected a multi-institutional cohort of 23 DDOC/UDOC and performed immunohistochemistry for core switch/sucrose nonfermentable (SWI/SNF) complex proteins (ARID1A, ARID1B, SMARCA4, and SMARCB1), mismatch repair (MMR) proteins, and p53. Array-based genome-wide DNA methylation and copy number variation analyses were performed on a subset of cases with comparison made to a previously reported cohort of undifferentiated endometrial carcinoma (UDEC), small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and tubo-ovarian high-grade serous carcinoma (HGSC). The age of all 23 patients with DDOC/UDOC ranged between 22 and 71 years (with an average age of 50 years), and a majority of them presented with extraovarian disease (16/23). Clinical follow-up was available for 19 patients. Except for 2 patients, the remaining 17 patients died from disease, with rapid disease progression resulting in mortality within a year in stage II-IV settings (median disease-specific survival of 3 months). Eighteen of 22 cases with interpretable immunohistochemistry results showed loss of expression of core SWI/SNF protein(s) that are expected to result in SWI/SNF complex inactivation as 10 exhibited coloss of ARID1A and ARID1B, 7 loss of SMARCA4, and 1 loss of SMARCB1. Six of 23 cases were MMR-deficient. Two of 20 cases exhibited mutation-type p53 immunoreactivity. Methylation profiles showed coclustering of DDOC/UDOC with UDEC, which collectively were distinct from SCCOHT and HGSC. However, DDOC/UDOC showed an intermediate degree of copy number variation, which was slightly greater, compared with SCCOHT but much less compared with HGSC. Overall, DDOC/UDOC, like its endometrial counterpart, is highly aggressive and is characterized by frequent inactivation of core SWI/SNF complex proteins and MMR deficiency. Its molecular profile overlaps with UDEC while being distinct from SCCOHT and HGSC.
MeSH term(s)	Female ; Humans ; Middle Aged ; Young Adult ; Adult ; Aged ; Tumor Suppressor Protein p53/genetics ; DNA Copy Number Variations ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Carcinoma/pathology ; Carcinoma, Ovarian Epithelial ; Endometrial Neoplasms/pathology ; Carcinoma, Small Cell ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; DNA Helicases/genetics ; DNA Helicases/metabolism ; Nuclear Proteins/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Brain Neoplasms ; Neoplastic Syndromes, Hereditary ; Colorectal Neoplasms
Chemical Substances	Tumor Suppressor Protein p53 ; Biomarkers, Tumor ; SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-) ; Nuclear Proteins ; Transcription Factors
Language	English
Publishing date	2023-11-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2023.100374
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