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Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing
PTEN is a tumor suppressor that negatively regulates the PI3K-AKT signaling pathway, which is implicated in the pathogenesis of endometrial carcinoma. Sanger sequencing has been considered to be the gold standard for detection of PTEN sequence abnormalities. However, this approach fails to address t...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341518/ https://www.ncbi.nlm.nih.gov/pubmed/22301702 http://dx.doi.org/10.1038/modpathol.2011.208 |
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author | Djordjevic, Bojana Hennessy, Bryan T. Li, Jie Barkoh, Bedia A. Luthra, Rajyalakshmi Mills, Gordon B. Broaddus, Russell R. |
author_facet | Djordjevic, Bojana Hennessy, Bryan T. Li, Jie Barkoh, Bedia A. Luthra, Rajyalakshmi Mills, Gordon B. Broaddus, Russell R. |
author_sort | Djordjevic, Bojana |
collection | PubMed |
description | PTEN is a tumor suppressor that negatively regulates the PI3K-AKT signaling pathway, which is implicated in the pathogenesis of endometrial carcinoma. Sanger sequencing has been considered to be the gold standard for detection of PTEN sequence abnormalities. However, this approach fails to address the epigenetic mechanisms that contribute to functional PTEN loss. Using a study cohort of 154 endometrioid and non-endometrioid endometrial carcinomas, we performed full-length PTEN sequencing and PTEN immunohistochemistry on each tumor. PTEN sequence abnormalities were detected in a significantly lower proportion of cases (43%) than PTEN protein loss (64%, p= 0.0004). Endometrioid tumors had a significantly higher proportion of PTEN sequence abnormalities and PTEN protein loss than non-endometrioid tumors. Within the latter group, PTEN sequence abnormalities and PTEN protein loss were most frequent in undifferentiated carcinomas, followed by mixed carcinomas; they were least frequent in carcinosarcomas. Overall, at least one PTEN sequence abnormality was detected in each exon, and the greatest number of sequence abnormalities was detected in exon 8. Pure endometrioid tumors had a significantly higher frequency of sequence abnormalities in exon 7 than did the non-endometrioid tumors (p=0.0199). Importantly, no mutational hotspots were identified. While PTEN protein loss by immunohistochemistry was identified in 89% of cases with a PTEN sequence abnormality, PTEN protein loss was detected by immunohistochemistry in 44% of cases classified as PTEN wildtype by sequencing. For the first time, we demonstrate that PTEN immunohistochemistry is able to identify the majority of cases with functional PTEN loss. However, PTEN immunohistochemistry also detects additional cases with PTEN protein loss that would otherwise be undetected by gene sequencing. Therefore, for clinical purposes, immunohistochemistry appears to be a preferable technique for identifying endometrial tumors with loss of PTEN function. |
format | Online Article Text |
id | pubmed-3341518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-33415182012-11-01 Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing Djordjevic, Bojana Hennessy, Bryan T. Li, Jie Barkoh, Bedia A. Luthra, Rajyalakshmi Mills, Gordon B. Broaddus, Russell R. Mod Pathol Article PTEN is a tumor suppressor that negatively regulates the PI3K-AKT signaling pathway, which is implicated in the pathogenesis of endometrial carcinoma. Sanger sequencing has been considered to be the gold standard for detection of PTEN sequence abnormalities. However, this approach fails to address the epigenetic mechanisms that contribute to functional PTEN loss. Using a study cohort of 154 endometrioid and non-endometrioid endometrial carcinomas, we performed full-length PTEN sequencing and PTEN immunohistochemistry on each tumor. PTEN sequence abnormalities were detected in a significantly lower proportion of cases (43%) than PTEN protein loss (64%, p= 0.0004). Endometrioid tumors had a significantly higher proportion of PTEN sequence abnormalities and PTEN protein loss than non-endometrioid tumors. Within the latter group, PTEN sequence abnormalities and PTEN protein loss were most frequent in undifferentiated carcinomas, followed by mixed carcinomas; they were least frequent in carcinosarcomas. Overall, at least one PTEN sequence abnormality was detected in each exon, and the greatest number of sequence abnormalities was detected in exon 8. Pure endometrioid tumors had a significantly higher frequency of sequence abnormalities in exon 7 than did the non-endometrioid tumors (p=0.0199). Importantly, no mutational hotspots were identified. While PTEN protein loss by immunohistochemistry was identified in 89% of cases with a PTEN sequence abnormality, PTEN protein loss was detected by immunohistochemistry in 44% of cases classified as PTEN wildtype by sequencing. For the first time, we demonstrate that PTEN immunohistochemistry is able to identify the majority of cases with functional PTEN loss. However, PTEN immunohistochemistry also detects additional cases with PTEN protein loss that would otherwise be undetected by gene sequencing. Therefore, for clinical purposes, immunohistochemistry appears to be a preferable technique for identifying endometrial tumors with loss of PTEN function. 2012-02-03 2012-05 /pmc/articles/PMC3341518/ /pubmed/22301702 http://dx.doi.org/10.1038/modpathol.2011.208 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Djordjevic, Bojana Hennessy, Bryan T. Li, Jie Barkoh, Bedia A. Luthra, Rajyalakshmi Mills, Gordon B. Broaddus, Russell R. Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing |
title | Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing |
title_full | Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing |
title_fullStr | Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing |
title_full_unstemmed | Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing |
title_short | Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing |
title_sort | clinical assessment of pten loss in endometrial carcinoma: immunohistochemistry out-performs gene sequencing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341518/ https://www.ncbi.nlm.nih.gov/pubmed/22301702 http://dx.doi.org/10.1038/modpathol.2011.208 |
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