Morphologic and genetic features of sarcomas : improving diagnosis and exploring biomarkers
Author: Zhang, Yifan
Date: 2022-09-23
Location: CCK lecture hall, Radiumhemmet, Karolinska University Hospital, Solna
Time: 09.00
Department: Inst för onkologi-patologi / Dept of Oncology-Pathology
View/ Open:
Thesis (2.496Mb)
Abstract
Sarcomas are malignant tumors of soft tissue and bone origin. They are a family of rare but diverse neoplasms which pose clinical challenges due to their heterogeneous properties. In order to increase our understanding of sarcoma biology, we are continuously reviewing clinical cohorts regarding morphological presentation and underlying genetic changes. This thesis focuses on translational research from improving diagnostics to exploring biomarkers in select sarcoma subtypes.
In Paper I we investigated fine needle aspirations of synovial sarcomas (SS) in order to identify common characteristics. Samples from SS displayed similar features such as abundant oval, round or spindle-shaped cells with pericapillary formation and pink background stroma. All tumors also harbored the pathognomonic fusion gene SYT-SSX, which can be detected by sequencing and is recommended to verify a diagnosis of SS.
In Paper II we investigated FNAs of clear cell chondrosarcomas (CCCS) in order to identify common characteristics. Samples from CCCS displayed similar features such as abundant clear cells with round nucleus and prominent nuclei, which separated it from its most common differential diagnosis chondroblastoma, a benign tumor. Due to the rarity of CCCS we also conducted a literature review and found that CCCS was more common in patients >25 and chondroblastoma more common in patients <25 years of age. There is however a significant overlap and a clear cutoff age cannot be established.
In Paper III we investigated the role of TERT promoter mutation in chondrosarcomas (CS). We found that TERT promoter mutation (C228T) was common in CS and was significantly correlated with higher tumor grade, increased risk of metastasis and tumor-related death, as well as a more aggressive course of disease. We also found that CS undergo branching evolution, as patients can have a wild-type primary tumor and a mutated metastasis or vice versa. As TERT promoter mutation status is easily detected by sequencing it can be useful as a prognostic biomarker.
In Paper IV we investigated the expression of PD-L1 in three common sarcoma types: liposarcoma (LS), undifferentiated pleomorphic sarcoma (UPS), and CS. We found that PD-L1 expression was most common in UPS, rare in LS and very rare in CS, but it did not correlate to metastasis or death from disease in any sarcoma subtype.
In Paper I we investigated fine needle aspirations of synovial sarcomas (SS) in order to identify common characteristics. Samples from SS displayed similar features such as abundant oval, round or spindle-shaped cells with pericapillary formation and pink background stroma. All tumors also harbored the pathognomonic fusion gene SYT-SSX, which can be detected by sequencing and is recommended to verify a diagnosis of SS.
In Paper II we investigated FNAs of clear cell chondrosarcomas (CCCS) in order to identify common characteristics. Samples from CCCS displayed similar features such as abundant clear cells with round nucleus and prominent nuclei, which separated it from its most common differential diagnosis chondroblastoma, a benign tumor. Due to the rarity of CCCS we also conducted a literature review and found that CCCS was more common in patients >25 and chondroblastoma more common in patients <25 years of age. There is however a significant overlap and a clear cutoff age cannot be established.
In Paper III we investigated the role of TERT promoter mutation in chondrosarcomas (CS). We found that TERT promoter mutation (C228T) was common in CS and was significantly correlated with higher tumor grade, increased risk of metastasis and tumor-related death, as well as a more aggressive course of disease. We also found that CS undergo branching evolution, as patients can have a wild-type primary tumor and a mutated metastasis or vice versa. As TERT promoter mutation status is easily detected by sequencing it can be useful as a prognostic biomarker.
In Paper IV we investigated the expression of PD-L1 in three common sarcoma types: liposarcoma (LS), undifferentiated pleomorphic sarcoma (UPS), and CS. We found that PD-L1 expression was most common in UPS, rare in LS and very rare in CS, but it did not correlate to metastasis or death from disease in any sarcoma subtype.
List of papers:
I. Y Zhang, S Wessman, J Wejde, E Tani and F Haglund de Flon. Synovial sarcoma diagnosed by fine needle aspiration cytology and molecular techniques during 10 years. Cytopathology. 2019;30(5): 504-509.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Y Zhang, Z Alagic, E Tani, M Skorpil, P Tsagkozis and F Haglund de Flon. Clear-cell chondrosarcomas: Fine-needle aspiration cytology, radiological findings, and patient demographics of a rare entity. Diagnostic Cytopathology. 2021; 49(1): 46-53.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Y Zhang, Y Chen, C Yang, N Seger, A Hesla, P Tsagkozis, O Larsson, Y Lin and F Haglund de Flon. TERT promoter mutation is an objective clinical marker for disease progression in chondrosarcoma. Modern Pathology. 2021;34(11): 2020-2027.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Y Zhang, Y Chen, A Papakonstantinou, P Tsagkozis, C Linder Stragliotto and F Haglund de Flon. Evaluating PD-L1 expression in undifferentiated pleomorphic sarcomas, liposarcomas and chondrosarcomas. Biomolecules. 2022; 12(2):292.
Fulltext (DOI)
Pubmed
View record in Web of Science®
I. Y Zhang, S Wessman, J Wejde, E Tani and F Haglund de Flon. Synovial sarcoma diagnosed by fine needle aspiration cytology and molecular techniques during 10 years. Cytopathology. 2019;30(5): 504-509.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Y Zhang, Z Alagic, E Tani, M Skorpil, P Tsagkozis and F Haglund de Flon. Clear-cell chondrosarcomas: Fine-needle aspiration cytology, radiological findings, and patient demographics of a rare entity. Diagnostic Cytopathology. 2021; 49(1): 46-53.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Y Zhang, Y Chen, C Yang, N Seger, A Hesla, P Tsagkozis, O Larsson, Y Lin and F Haglund de Flon. TERT promoter mutation is an objective clinical marker for disease progression in chondrosarcoma. Modern Pathology. 2021;34(11): 2020-2027.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Y Zhang, Y Chen, A Papakonstantinou, P Tsagkozis, C Linder Stragliotto and F Haglund de Flon. Evaluating PD-L1 expression in undifferentiated pleomorphic sarcomas, liposarcomas and chondrosarcomas. Biomolecules. 2022; 12(2):292.
Fulltext (DOI)
Pubmed
View record in Web of Science®
Institution: Karolinska Institutet
Supervisor: Haglund de Flon, Felix
Co-supervisor: Lin, Yingbo; Larsson, Olle
Issue date: 2022-08-16
Rights:
Publication year: 2022
ISBN: 978-91-8016-455-9
Statistics
Total Visits
Views | |
---|---|
Morphologic ... | 306 |
Total Visits Per Month
October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | April 2024 | |
---|---|---|---|---|---|---|---|
Morphologic ... | 23 | 18 | 20 | 17 | 18 | 26 | 12 |
File Visits
Views | |
---|---|
Thesis_Yifan_Zhang.pdf | 122 |
Thesis_Zhang_0803_new.pdf | 1 |
Top country views
Views | |
---|---|
Ireland | 82 |
Sweden | 59 |
United Kingdom | 49 |
United States | 28 |
South Korea | 10 |
China | 7 |
Germany | 7 |
Russia | 7 |
India | 5 |
Japan | 4 |
Top cities views
Views | |
---|---|
Dublin | 82 |
Stockholm | 10 |
Norrköping | 7 |
Ashburn | 5 |
Bromma | 5 |
Moscow | 5 |
Hanoi | 4 |
Umeå | 4 |
Singapore | 3 |
Solna | 3 |