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

Clinical decisions Colorectal cancer Immunohistochemistry Phosphorylated signal transducer and activator of transcription-3 (pSTAT3) Primary cancer paired with liver metastasis

Journal

Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619

Informations de publication

Date de publication:
Feb 2021
Historique:
received: 11 11 2020
revised: 07 12 2020
accepted: 08 12 2020
pubmed: 21 12 2020
medline: 21 12 2020
entrez: 20 12 2020
Statut: ppublish

Résumé

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). 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 33341488
pii: S1936-5233(20)30488-5
doi: 10.1016/j.tranon.2020.100996
pmc: PMC7750168
pii:
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100996

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Esmeralda C Marginean (EC)

The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa ON K1H 8L6 Canada; Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9. Electronic address: celia.marginean@providence.org.

Joanna Gotfrit (J)

The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa ON K1H 8L6 Canada; Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9. Electronic address: jgotfrit@toh.ca.

Horia Marginean (H)

The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa ON K1H 8L6 Canada; Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9. Electronic address: hmarginean@toh.ca.

Daniel W Yokom (DW)

The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa ON K1H 8L6 Canada; Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9. Electronic address: dwyokom@gmail.com.

Justin J Bateman (JJ)

Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9; The Ottawa Hospital, Department of Pathology, 501 Smyth Road, Ottawa ON K1H 8L6 Canada. Electronic address: jbateman@toh.ca.

Manijeh Daneshmand (M)

The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa ON K1H 8L6 Canada; Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9. Electronic address: manijeh_d@hotmail.com.

Shelly Sud (S)

The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa ON K1H 8L6 Canada; Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9. Electronic address: shellysud@me.com.

Allen M Gown (AM)

PhenoPath Laboratories, 551 N. 34th Street Seattle 98103 USA. Electronic address: gown@phenopath.com.

Derek Jonker (D)

The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa ON K1H 8L6 Canada; Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9. Electronic address: djonker@toh.ca.

Timothy Asmis (T)

The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa ON K1H 8L6 Canada; Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9. Electronic address: tasmis@toh.ca.

Rachel A Goodwin (RA)

The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa ON K1H 8L6 Canada; Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, ON K1Y 4E9. Electronic address: rgoodwin@toh.ca.

Classifications MeSH