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Phosphorylated transducer and activator of transcription-3 (pSTAT3) immunohistochemical expression in paired primary and metastatic colorectal cancer

BACKGROUND: Signal Transducer and Activator of Transcription-3 (STAT3) mediates cellular functions. We assessed the IHC expression of phosphorylated STAT3 (pSTAT3) in paired primary tumors and liver metastases in patients with advanced stage colorectal cancer (CRC). METHODS: We included patients wit...

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Autores principales: Marginean, Esmeralda C., Gotfrit, Joanna, Marginean, Horia, Yokom, Daniel W., Bateman, Justin J., Daneshmand, Manijeh, Sud, Shelly, Gown, Allen M., Jonker, Derek, Asmis, Timothy, Goodwin, Rachel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750168/
https://www.ncbi.nlm.nih.gov/pubmed/33341488
http://dx.doi.org/10.1016/j.tranon.2020.100996
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author Marginean, Esmeralda C.
Gotfrit, Joanna
Marginean, Horia
Yokom, Daniel W.
Bateman, Justin J.
Daneshmand, Manijeh
Sud, Shelly
Gown, Allen M.
Jonker, Derek
Asmis, Timothy
Goodwin, Rachel A.
author_facet Marginean, Esmeralda C.
Gotfrit, Joanna
Marginean, Horia
Yokom, Daniel W.
Bateman, Justin J.
Daneshmand, Manijeh
Sud, Shelly
Gown, Allen M.
Jonker, Derek
Asmis, Timothy
Goodwin, Rachel A.
author_sort Marginean, Esmeralda C.
collection PubMed
description BACKGROUND: Signal Transducer and Activator of Transcription-3 (STAT3) mediates cellular functions. We assessed the IHC expression of phosphorylated STAT3 (pSTAT3) in paired primary tumors and liver metastases in patients with advanced stage colorectal cancer (CRC). METHODS: We included patients with tissue blocks available from both the primary CRC and a surgically resected liver metastasis. The IHC pSTAT3 expression agreement was measured using Cohen's kappa statistic. RESULTS: The study included 103 patients, 55% male, median age was 64. 43% tumors originated in rectum, and 63% of the primary tumors were synchronous. Expression of pSTAT3 was 76% in liver metastases and 71% in primary tumors. A difference in pSTAT3 staining between the primary tumor and liver metastases was noted in 64%. There was lost expression of pSTAT3 in the liver metastases in 28% and gained expression in 36% of cases compared to the primary. The kappa statistic comparing agreement between staining patterns of the primary tumors and liver metastases was a “less-than-chance”, at -0.02. Median survival was 4.9 years, with no difference in survival outcomes by pSTAT3 expression in the primary tumor or liver metastases. DISCUSSION: STAT3 is not a prognostic marker in the selective setting of metastatic CRC to liver, but it may remain a potential therapeutic target given most liver metastases expressed pSTAT3. Discordant pSTAT3 expression in between primary tumors and paired liver metastases suggests that use of this class of drug to treat liver predominant metastatic colorectal cancer in a biomarker-driven approach may require confirmatory liver tumor biopsy.
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spelling pubmed-77501682020-12-28 Phosphorylated transducer and activator of transcription-3 (pSTAT3) immunohistochemical expression in paired primary and metastatic colorectal cancer Marginean, Esmeralda C. Gotfrit, Joanna Marginean, Horia Yokom, Daniel W. Bateman, Justin J. Daneshmand, Manijeh Sud, Shelly Gown, Allen M. Jonker, Derek Asmis, Timothy Goodwin, Rachel A. Transl Oncol Original Research BACKGROUND: Signal Transducer and Activator of Transcription-3 (STAT3) mediates cellular functions. We assessed the IHC expression of phosphorylated STAT3 (pSTAT3) in paired primary tumors and liver metastases in patients with advanced stage colorectal cancer (CRC). METHODS: We included patients with tissue blocks available from both the primary CRC and a surgically resected liver metastasis. The IHC pSTAT3 expression agreement was measured using Cohen's kappa statistic. RESULTS: The study included 103 patients, 55% male, median age was 64. 43% tumors originated in rectum, and 63% of the primary tumors were synchronous. Expression of pSTAT3 was 76% in liver metastases and 71% in primary tumors. A difference in pSTAT3 staining between the primary tumor and liver metastases was noted in 64%. There was lost expression of pSTAT3 in the liver metastases in 28% and gained expression in 36% of cases compared to the primary. The kappa statistic comparing agreement between staining patterns of the primary tumors and liver metastases was a “less-than-chance”, at -0.02. Median survival was 4.9 years, with no difference in survival outcomes by pSTAT3 expression in the primary tumor or liver metastases. DISCUSSION: STAT3 is not a prognostic marker in the selective setting of metastatic CRC to liver, but it may remain a potential therapeutic target given most liver metastases expressed pSTAT3. Discordant pSTAT3 expression in between primary tumors and paired liver metastases suggests that use of this class of drug to treat liver predominant metastatic colorectal cancer in a biomarker-driven approach may require confirmatory liver tumor biopsy. Neoplasia Press 2020-12-17 /pmc/articles/PMC7750168/ /pubmed/33341488 http://dx.doi.org/10.1016/j.tranon.2020.100996 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Marginean, Esmeralda C.
Gotfrit, Joanna
Marginean, Horia
Yokom, Daniel W.
Bateman, Justin J.
Daneshmand, Manijeh
Sud, Shelly
Gown, Allen M.
Jonker, Derek
Asmis, Timothy
Goodwin, Rachel A.
Phosphorylated transducer and activator of transcription-3 (pSTAT3) immunohistochemical expression in paired primary and metastatic colorectal cancer
title Phosphorylated transducer and activator of transcription-3 (pSTAT3) immunohistochemical expression in paired primary and metastatic colorectal cancer
title_full Phosphorylated transducer and activator of transcription-3 (pSTAT3) immunohistochemical expression in paired primary and metastatic colorectal cancer
title_fullStr Phosphorylated transducer and activator of transcription-3 (pSTAT3) immunohistochemical expression in paired primary and metastatic colorectal cancer
title_full_unstemmed Phosphorylated transducer and activator of transcription-3 (pSTAT3) immunohistochemical expression in paired primary and metastatic colorectal cancer
title_short Phosphorylated transducer and activator of transcription-3 (pSTAT3) immunohistochemical expression in paired primary and metastatic colorectal cancer
title_sort phosphorylated transducer and activator of transcription-3 (pstat3) immunohistochemical expression in paired primary and metastatic colorectal cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750168/
https://www.ncbi.nlm.nih.gov/pubmed/33341488
http://dx.doi.org/10.1016/j.tranon.2020.100996
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