Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Marginean EC

PROVIDER: S-EPMC7750168 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Marginean Esmeralda C EC Gotfrit Joanna J Marginean Horia H Yokom Daniel W DW Bateman Justin J JJ Daneshmand Manijeh M Sud Shelly S Gown Allen M AM Jonker Derek D Asmis Timothy T Goodwin Rachel A RA

Translational oncology 20201217 2

<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results< ...[more]

PMID: 33341488

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Project description:Background: Activated signal transducer and activator of transcription 3 (pSTAT3) is often present in breast cancer, but its prognostic impact is still unclear. We investigated how breast tumor-specific pSTAT3Y705 levels are associated with patient and tumor characteristics and risk of recurrence. Materials and Methods: Primary breast cancer patients without preoperative treatment were included preoperatively. The patients were treated in Lund, Sweden, in 2002-2012 and followed until 2016. Levels of pSTAT3Y705 were evaluated in 867 tumors using tissue microarrays with immunohistochemistry and categorized according to the H-score as negative (0-9; 24.2%), intermediate (10-150; 69.9%), and high (160-300; 5.9%). Results: Patients were followed for up to 13 years, and 137 recurrences (88 distant) were recorded. Higher pSTAT3Y705 levels were associated with patient characteristics including younger age, any alcohol consumption, higher age at first child birth, and smaller body size, as well as tumor characteristics including smaller tumor size, lower histological grade, lymph node negativity, progesterone receptor positivity, and HER2 negativity (all P trends ? 0.04). Higher pSTAT3Y705 levels were associated with lower risk of early recurrences (LogRank P trend = 0.10; 5-year LogRank P trend = 0.004) and distant metastases (LogRank P trend = 0.045; 5-year LogRank P trend = 0.0007), but this was not significant in the multivariable models. There was significant effect modification between tamoxifen treatment and pSTAT3Y705 negativity on the recurrence risk in chemonaïve patients with estrogen receptor positive tumors [adjusted hazard ratio (HR) 0.38; P interaction = 0.046]. Conclusion: Higher pSTAT3Y705 levels were associated with several patient and tumor characteristics that are mainly associated with good prognosis and a tendency toward lower risk for early recurrences. In the future, these results may help guide the selection of patients for trials with drugs targeting the STAT3 pathway.

Dataset Information

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

Background

Methods

Results

Discussion

Publications

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

Similar Datasets

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