The Overexpression of Programmed Death-Ligand 2 in Uterine Adenosarcoma: Correlation with High-Grade Morphology, Mutant Type TP53 Expression and Clinical Outcomes

Immunotherapy involving the programmed death-1 (PD-1)/the programmed death-ligand (PD-1/PD-L) blockade is an understudied tumor therapy approach in cases of adenosarcoma. PD-L1 and PD-L2, and tumor protein p53 (p53) were examined in 20 uterine adenosarcoma cases, and tumor-infiltrating lymphocytes a...

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Veröffentlicht in:International journal of surgical pathology 2023-06, Vol.31 (4), p.352-364
Hauptverfasser: Ok Atılgan, Alev, Yılmaz Akçay, Eda, Özen, Özlem, Haberal Reyhan, A. Nihan, Ayhan, Ali
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container_issue 4
container_start_page 352
container_title International journal of surgical pathology
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creator Ok Atılgan, Alev
Yılmaz Akçay, Eda
Özen, Özlem
Haberal Reyhan, A. Nihan
Ayhan, Ali
description Immunotherapy involving the programmed death-1 (PD-1)/the programmed death-ligand (PD-1/PD-L) blockade is an understudied tumor therapy approach in cases of adenosarcoma. PD-L1 and PD-L2, and tumor protein p53 (p53) were examined in 20 uterine adenosarcoma cases, and tumor-infiltrating lymphocytes and tumor-associated macrophages were counted in tumor tissue using immunohistochemistry. While CPS PD-L1 positivity with 1% and 10% cut-off values was observed in 40% and 10% of tumors, respectively, CPS PD-L2 positivity with 1%, 10% and 50% cut-off values was observed in 100%, 85% and 50% of the tumors, respectively. The CPS PD-L2 positivity with a 50% cut-off value was positively correlated with tumor grade and the presence of sarcomatous overgrowth and lymphovascular invasion (LVI) (p = 0.025, p = 0.025, and p = 0.025, respectively). Nine of 11 high-grade adenosarcomas and none of the low-grade adenosarcomas showed mutant type p53 expression (p = 0.000). However, PD-L1 expression and tumor-infiltrating immune cells did not correlate with clinicopathological parameters. The CPS PD-L2 positivity with a 50% cut-off value was also positively correlated with mutant type p53 expression (p = 0.024) and tumor-associated macrophages density (p = 0.024). The CPS PD-L2 positivity with a 50% cut-off value and mutant type p53 expression were associated with shorter disease-free survival and shorter overall survival. The high density of tumor-associated macrophages and low density of tumor-infiltrating lymphocytes were also associated with shorter disease-free survival and overall survival (p 
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The CPS PD-L2 positivity with a 50% cut-off value was positively correlated with tumor grade and the presence of sarcomatous overgrowth and lymphovascular invasion (LVI) (p = 0.025, p = 0.025, and p = 0.025, respectively). Nine of 11 high-grade adenosarcomas and none of the low-grade adenosarcomas showed mutant type p53 expression (p = 0.000). However, PD-L1 expression and tumor-infiltrating immune cells did not correlate with clinicopathological parameters. The CPS PD-L2 positivity with a 50% cut-off value was also positively correlated with mutant type p53 expression (p = 0.024) and tumor-associated macrophages density (p = 0.024). The CPS PD-L2 positivity with a 50% cut-off value and mutant type p53 expression were associated with shorter disease-free survival and shorter overall survival. 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The high density of tumor-associated macrophages and low density of tumor-infiltrating lymphocytes were also associated with shorter disease-free survival and overall survival (p &lt; 0.05).These results suggested that the CPS PD-L2 positivity with a 50% cut-off value, p53 mutation and tumor microenvironment played an essential role in the progression of uterine adenosarcomas.</description><subject>Adenosarcoma</subject><subject>B7-H1 Antigen - genetics</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Ligands</subject><subject>Prognosis</subject><subject>Tumor Microenvironment</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumors</subject><issn>1066-8969</issn><issn>1940-2465</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAURS1ERUvhA9ggS2xYkOLnxE7MrhpKW2mq6WK6jpz4JXGVxMFOgPkdvhSPplCJqis_2efea71LyDtgZwB5_hmYlIWSinNgSkChXpATUBlLeCbFyzjH92QPHJPXIdwzxrjk8IocpyKTMhfqhPzedkg3P9Djr8ljCNaN1DX01rvW62FAQ7-inrtkbVs9GsqpHendjN6OSM8Nji5oX7tBf6Er5z32et47_LRzR69s2yWXXhukN85Pnetdu_tEb5ZZjzPd7iak21uR0ovH5H3EqrejrXVPN8scnTG8IUeN7gO-fThPyd23i-3qKllvLq9X5-ukTmUxJ6nEtDGQ1SmkVaPyiolaxZtC1QUzMsMGNHLglRQFsMqg0kUDaKqo0RpMeko-Hnwn774vGOZysKHGvtcjuiWUXAoBjDPJI_rhP_TeLX6Mvyt5AZDlMlNFpOBA1d6F4LEpJ28H7XclsHJfYPmkwKh5_-C8VHH7_xR_G4vA2QEIusXH2Ocd_wDNEKSL</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Ok Atılgan, Alev</creator><creator>Yılmaz Akçay, Eda</creator><creator>Özen, Özlem</creator><creator>Haberal Reyhan, A. 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While CPS PD-L1 positivity with 1% and 10% cut-off values was observed in 40% and 10% of tumors, respectively, CPS PD-L2 positivity with 1%, 10% and 50% cut-off values was observed in 100%, 85% and 50% of the tumors, respectively. The CPS PD-L2 positivity with a 50% cut-off value was positively correlated with tumor grade and the presence of sarcomatous overgrowth and lymphovascular invasion (LVI) (p = 0.025, p = 0.025, and p = 0.025, respectively). Nine of 11 high-grade adenosarcomas and none of the low-grade adenosarcomas showed mutant type p53 expression (p = 0.000). However, PD-L1 expression and tumor-infiltrating immune cells did not correlate with clinicopathological parameters. The CPS PD-L2 positivity with a 50% cut-off value was also positively correlated with mutant type p53 expression (p = 0.024) and tumor-associated macrophages density (p = 0.024). The CPS PD-L2 positivity with a 50% cut-off value and mutant type p53 expression were associated with shorter disease-free survival and shorter overall survival. The high density of tumor-associated macrophages and low density of tumor-infiltrating lymphocytes were also associated with shorter disease-free survival and overall survival (p &lt; 0.05).These results suggested that the CPS PD-L2 positivity with a 50% cut-off value, p53 mutation and tumor microenvironment played an essential role in the progression of uterine adenosarcomas.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>35466759</pmid><doi>10.1177/10668969221095189</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-8595-8880</orcidid></addata></record>
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subjects Adenosarcoma
B7-H1 Antigen - genetics
B7-H1 Antigen - metabolism
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Female
Humans
Ligands
Prognosis
Tumor Microenvironment
Tumor Suppressor Protein p53 - genetics
Tumors
title The Overexpression of Programmed Death-Ligand 2 in Uterine Adenosarcoma: Correlation with High-Grade Morphology, Mutant Type TP53 Expression and Clinical Outcomes
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