Altered PTEN Expression as a Diagnostic Marker for the Earliest Endometrial Precancers
Abstract
Background PTEN tumor suppressor gene mutations are the most frequent genetic lesions in endometrial adenocarcinomas of the endometrioid subtype. Testing the hypothesis that altered PTEN function precedes the appearance of endometrial adenocarcinoma has been difficult, however, partly because of uncertainties in precancer diagnosis. Methods Two series of endometrial cancer and precancer (endometrial intraepithelial neoplasia, as diagnosed by computerized morphometric analysis) tissue samples were studied, one for PTEN mutations by the use of denaturing gradient gel electrophoresis and another for PTEN protein expression by immunohistochemistry. Endometria altered by high estrogen levels that are unopposed by progestins-conditions known to increase cancer risk-were also studied by immunohistochemistry. Fisher's exact test was used for statistical analysis. Results The PTEN mutation rate was 83% (25 of 30) in endometrioid endometrial adenocarcinomas and 55% (16 of 29) in precancers, and the difference in number of mutations was statistically significant (two-sided P =.025). No normal endometria showed PTEN mutations. Although most precancers and cancers had a mutation in only one PTEN allele, endometrioid endometrial adenocarcinomas showed complete loss of PTEN protein expression in 61% (20 of 33) of cases, and 97% (32 of 33) showed at least some diminution in expression. Cancers and most precancers exhibited contiguous groups of PTEN-negative glands, while endometria altered b…
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PTEN mutations are often observed early during tumorigenesis, whereas a complete loss is considered to be a late event.
“PTEN mutations are often observed early during tumorigenesis, whereas a complete loss is considered to be a late event48.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [48]
The toolkit has a significant advantage to generate isogenic models of novel mutations in early tumorigenesis.
“Taken together, these results demonstrate the significant advantage the toolkit we have developed in this study has to generate isogenic models of novel mutations in early tumorigenesis48,50–52.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [48]
This hypothesis had never before been tested in an isogenic model.
“While this hypothesis has been previously proposed48,50–52, it had never before been tested in an isogenic model.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [48]
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A functional genetic screen defines the AKT-induced senescence signaling network
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One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids
Geurts, M. H., Gandhi, S., Boretto, M. G., Akkerman, N., Derks, L. L. M., van Son, G., Celotti, M., Harshuk-Shabso, S., Peci, F., Begthel, H., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40701-3 · Cited by 66 · see citing works
“While this hypothesis has been previously proposed 48,50 – 52 , it had never before been tested in an isogenic model.”
- Authors
- Mutter, G. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Mutter, G. L.
- ORCID
- Mutter, G. L.
- Venue
- Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-06-07
- Volume
- 92
- Issue
- 11
- Pages
- 924-930
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2113190292
- Cited by
- 829
- References
- 2
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 19 · 2023: 22 · 2022: 26 · 2021: 30 · 2020: 18 · 2019: 34 · 2018: 25 · 2017: 33 · 2016: 33 · 2015: 38 · 2014: 41 · 2013: 41 · 2012: 45
- FWCI
- 39.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Keywords
- PTEN, endometrial adenocarcinoma, endometrial intraepithelial neoplasia, tumor suppressor mutations, endometrial carcinogenesis, unopposed estrogen, precancerous lesions, diagnostic biomarkers, endometrioid carcinoma
- MeSH terms
- Diagnosis, Differential, DNA Mutational Analysis, Female, Humans, Immunohistochemistry, Phosphoric Monoester Hydrolases, Precancerous Conditions, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Polymerase Chain Reaction, Genes, Tumor Suppressor, Endometrial Neoplasms, DNA Primers, Germ-Line Mutation, Tumor Suppressor Proteins, PTEN Phosphohydrolase
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