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PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma
1Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
Background:
PTEN gene at chromosomes 10q23.3 is a tumour suppressor gene that is inactivated in many types of human cancers. The known mechanisms of PTEN inactivation are rendered to mutation, epigenetic silencing by aberrant methylation or gene deletion. Although PTEN role has been documented in many cancers, PTEN alteration in papillary thyroid carcinoma (PTC) has not been fully elucidated. The aim of this study is to comprehensively investigate PTEN alterations in a large cohort of Middle Eastern papillary thyroid cancer by immunohistochemistry and fluorescent in situ hybridisation (FISH).
Methods:
PTEN protein expression was analysed by immunohistochemistry in a tissue microarray (TMA) format in a large cohort of more than 1000 patients with papillary thyroid cancer. Copy number changes in PTEN were analysed by FISH and data were correlated with clinicopathological parameters along with survival analysis.
Results:
PTEN inactivation reflected by complete absence of staining was seen in 24.5% of PTC samples, whereas PTEN deletion was seen only in 4.8% of the tested samples by FISH. No association was seen between PTEN loss of protein expression and PTEN gene deletion. However, interestingly, PTEN loss of expression was significantly associated with the follicular variant subset of papillary thyroid cancer.
Conclusion:
Our study confirmed that PTEN might have a role in pathogenesis in a subset of PTC. PTEN loss of protein expression is a more common event in follicular variant of papillary thyroid cancer. Lack of association between PTEN loss of protein expression and PTEN gene deletion might indicate that gene deletion may not be the sole cause for PTEN loss of expression and these results might raise the possibility of other mechanism such as promoter methylation-mediated gene silencing to be responsible for PTEN inactivation.
Insights
PTEN gene alterations are common in papillary thyroid cancer (PTC), particularly the follicular variant. Loss of PTEN protein expression, often without gene deletion, suggests other inactivation mechanisms may be involved in PTC development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The PTEN gene, a crucial tumor suppressor, is frequently inactivated in various cancers.
- Mechanisms of PTEN inactivation include mutation, methylation, and deletion.
- PTEN's specific role in papillary thyroid carcinoma (PTC) remains incompletely understood.
Purpose of the Study:
- To investigate PTEN alterations in a large cohort of Middle Eastern papillary thyroid cancer patients.
- To analyze PTEN protein expression and gene copy number changes.
- To correlate PTEN alterations with clinicopathological features and patient survival.
Main Methods:
- Immunohistochemistry (IHC) on a tissue microarray (TMA) of over 1000 PTC samples to assess PTEN protein expression.
- Fluorescent in situ hybridization (FISH) to detect PTEN gene copy number alterations.
- Statistical analysis correlating PTEN status with clinicopathological parameters and survival data.
Main Results:
- PTEN protein loss (complete absence of staining) was observed in 24.5% of PTC samples.
- PTEN gene deletion was detected in only 4.8% of samples via FISH.
- PTEN loss of expression showed a significant association with the follicular variant of PTC, but not with gene deletion.
Conclusions:
- PTEN plays a role in the pathogenesis of a subset of PTC.
- Loss of PTEN protein expression is more prevalent in the follicular variant of PTC.
- The lack of correlation between PTEN loss and gene deletion suggests alternative inactivation mechanisms, such as promoter methylation, may be involved.
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