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Uterine serous carcinoma: assessing association between genomics and patterns of metastasis

BACKGROUND: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial carcinoma which has been increasing at alarming rates, particularly among Asian, Hispanic and Black women. USC has not been well characterized in terms of mutational status, pattern of metastases and survival. OBJECTI...

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Autores principales: Alessandrino, Francesco, Goncalves, Nicole, Metalonis, Sarah Wishnek, Luna, Cibele, Mason, Matthew M., Lyu, Jiangnan, Huang, Marilyn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203475/
https://www.ncbi.nlm.nih.gov/pubmed/37228503
http://dx.doi.org/10.3389/fonc.2023.1066427
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author Alessandrino, Francesco
Goncalves, Nicole
Metalonis, Sarah Wishnek
Luna, Cibele
Mason, Matthew M.
Lyu, Jiangnan
Huang, Marilyn
author_facet Alessandrino, Francesco
Goncalves, Nicole
Metalonis, Sarah Wishnek
Luna, Cibele
Mason, Matthew M.
Lyu, Jiangnan
Huang, Marilyn
author_sort Alessandrino, Francesco
collection PubMed
description BACKGROUND: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial carcinoma which has been increasing at alarming rates, particularly among Asian, Hispanic and Black women. USC has not been well characterized in terms of mutational status, pattern of metastases and survival. OBJECTIVE: To investigate the association between sites of recurrence and metastases of USC, mutational status, race, and overall survival (OS). METHODS: This single-center retrospective study evaluated patients with biopsy-proven USC that underwent genomic testing between January 2015 and July 2021. Association between genomic profile and sites of metastases or recurrence was performed using χ2 or Fisher’s exact test. Survival curves for ethnicity and race, mutations, sites of metastasis/recurrence were estimated using the Kaplan-Meier method and compared with log-rank test. Cox proportional hazard regression models were used to examine the association between OS with age, race, ethnicity, mutational status, and sites of metastasis/recurrence. Statistical analyses were performed using SAS Software Version 9.4. RESULTS: The study included 67 women (mean age 65.8 years, range 44-82) with 52 non-Hispanic women (78%) and 33 Black women (49%). The most common mutation was TP53 (55/58 women, 95%). The peritoneum was the most common site of metastasis (29/33, 88%) and recurrence (8/27, 30%). PR expression was more common in women with nodal metastases (p=0.02) and non-Hispanic women (p=0.01). ERBB2 alterations were more common in women with vaginal cuff recurrence (p=0.02), while PIK3CA mutation was more common in women with liver metastases (p=0.048). ARID1A mutation and presence of recurrence or metastases to the liver were associated with lower OS (Hazard Ratio (HR): 31.87; 95%CI: 3.21, 316.9; p<0.001 and HR: 5.66; 95%CI: 1.2, 26.79; p=0.01, respectively). In the bivariable Cox model, the presence of metastasis/recurrence to the liver and/or the peritoneum were both independent significant predictors of OS (HR: 9.8; 95%CI: 1.85-52.7; p=0.007 and HR: 2.7; 95%CI: 1.02-7.1; p=0.04, respectively). CONCLUSIONS: TP53 is often mutated in USC, which most commonly metastasize and recur in the peritoneum. OS was shorter in women with ARID1A mutations and with metastasis/recurrence to the liver. The presence of metastasis/recurrence to liver and/or peritoneum were independently associated with shorter OS.
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spelling pubmed-102034752023-05-24 Uterine serous carcinoma: assessing association between genomics and patterns of metastasis Alessandrino, Francesco Goncalves, Nicole Metalonis, Sarah Wishnek Luna, Cibele Mason, Matthew M. Lyu, Jiangnan Huang, Marilyn Front Oncol Oncology BACKGROUND: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial carcinoma which has been increasing at alarming rates, particularly among Asian, Hispanic and Black women. USC has not been well characterized in terms of mutational status, pattern of metastases and survival. OBJECTIVE: To investigate the association between sites of recurrence and metastases of USC, mutational status, race, and overall survival (OS). METHODS: This single-center retrospective study evaluated patients with biopsy-proven USC that underwent genomic testing between January 2015 and July 2021. Association between genomic profile and sites of metastases or recurrence was performed using χ2 or Fisher’s exact test. Survival curves for ethnicity and race, mutations, sites of metastasis/recurrence were estimated using the Kaplan-Meier method and compared with log-rank test. Cox proportional hazard regression models were used to examine the association between OS with age, race, ethnicity, mutational status, and sites of metastasis/recurrence. Statistical analyses were performed using SAS Software Version 9.4. RESULTS: The study included 67 women (mean age 65.8 years, range 44-82) with 52 non-Hispanic women (78%) and 33 Black women (49%). The most common mutation was TP53 (55/58 women, 95%). The peritoneum was the most common site of metastasis (29/33, 88%) and recurrence (8/27, 30%). PR expression was more common in women with nodal metastases (p=0.02) and non-Hispanic women (p=0.01). ERBB2 alterations were more common in women with vaginal cuff recurrence (p=0.02), while PIK3CA mutation was more common in women with liver metastases (p=0.048). ARID1A mutation and presence of recurrence or metastases to the liver were associated with lower OS (Hazard Ratio (HR): 31.87; 95%CI: 3.21, 316.9; p<0.001 and HR: 5.66; 95%CI: 1.2, 26.79; p=0.01, respectively). In the bivariable Cox model, the presence of metastasis/recurrence to the liver and/or the peritoneum were both independent significant predictors of OS (HR: 9.8; 95%CI: 1.85-52.7; p=0.007 and HR: 2.7; 95%CI: 1.02-7.1; p=0.04, respectively). CONCLUSIONS: TP53 is often mutated in USC, which most commonly metastasize and recur in the peritoneum. OS was shorter in women with ARID1A mutations and with metastasis/recurrence to the liver. The presence of metastasis/recurrence to liver and/or peritoneum were independently associated with shorter OS. Frontiers Media S.A. 2023-05-09 /pmc/articles/PMC10203475/ /pubmed/37228503 http://dx.doi.org/10.3389/fonc.2023.1066427 Text en Copyright © 2023 Alessandrino, Goncalves, Metalonis, Luna, Mason, Lyu and Huang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Alessandrino, Francesco
Goncalves, Nicole
Metalonis, Sarah Wishnek
Luna, Cibele
Mason, Matthew M.
Lyu, Jiangnan
Huang, Marilyn
Uterine serous carcinoma: assessing association between genomics and patterns of metastasis
title Uterine serous carcinoma: assessing association between genomics and patterns of metastasis
title_full Uterine serous carcinoma: assessing association between genomics and patterns of metastasis
title_fullStr Uterine serous carcinoma: assessing association between genomics and patterns of metastasis
title_full_unstemmed Uterine serous carcinoma: assessing association between genomics and patterns of metastasis
title_short Uterine serous carcinoma: assessing association between genomics and patterns of metastasis
title_sort uterine serous carcinoma: assessing association between genomics and patterns of metastasis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203475/
https://www.ncbi.nlm.nih.gov/pubmed/37228503
http://dx.doi.org/10.3389/fonc.2023.1066427
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