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Updated: Jun 10, 2026
A Next-generation Tissue Microarray (ngTMA) Protocol for Biomarker Studies
Published on: September 23, 2014
Immunohistochemical examination of the mTORC1 pathway in high grade prostatic intraepithelial neoplasia (HGPIN) and
Sevan Evren1, Arthur Dermen, Gina Lockwood
1Department of Laboratory Medicine, University Health Network, Toronto, ON, Canada.
Background:
The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and a key regulator of protein synthesis and growth and is upregulated in many cancers. mTOR is activated by AKT phosphorylation (p-mTOR). p-mTOR associates with regulatory-associated protein of TOR (RAPTOR), forming the mTORC1 complex. mTORC1 promotes the activation of p70 ribosomal protein s6 kinase 1 (p70(S6K1)) and ribosomal protein s6 (RPS6). Upregulation of this pathway can lead to an aberrant increase in cell growth and metabolism characteristic of malignant transformation.
Methods:
This study presents the immunohistochemical (IHC) expression of the mTORC1 pathway in prostate neoplasia. The expression of p-mTOR and RAPTOR and p-p70(S6K1) and p-RPS6 were examined in HGPIN and PCa using tissue microarrays (TMA). Since each case in our TMAs was represented by three tissue cores, we quantified the IHC intratumoral heterogeneity of mTOR expression. This extensive analysis is the first detailed assessment documenting the IHC heterogeneity of mTOR expression in HGPIN and prostate cancer and represents the first IHC description of the mTORC1 pathway in HGPIN and PCa.
Results:
A Cochran-Armitage analysis demonstrated decreasing p-mTOR activity progressing from PIN through GL6 and GL7 to HG PCa. There was considerable intratumoral IHC heterogeneity within an individual patient. However, a statistically significant correlation was observed between p-mTOR, p-p70(S6K1), and p-RPS6 in each representative core.
Conclusion:
mTOR inhibitors may be an effective treatment for HGPIN and PCa. The extent of mTOR expression in an individual patient would determine the effective use of mTOR inhibitors as a potential therapeutic strategy.
Insights
The mammalian target of rapamycin (mTOR) pathway is upregulated in prostate cancer. mTOR inhibitors show potential as a treatment for high-grade prostatic intraepithelial neoplasia and prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Signaling
Background:
- The mammalian target of rapamycin (mTOR) pathway regulates cell growth and protein synthesis.
- mTOR pathway dysregulation is implicated in various cancers, including prostate cancer.
- The mTORC1 complex, comprising p-mTOR and RAPTOR, activates downstream targets like p70(S6K1) and RPS6, promoting cell proliferation.
Purpose of the Study:
- To investigate the immunohistochemical (IHC) expression of the mTORC1 pathway in prostate neoplasia.
- To assess the intratumoral heterogeneity of mTOR pathway expression in high-grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PCa).
Main Methods:
- Immunohistochemistry (IHC) was employed to examine the expression of p-mTOR, RAPTOR, p-p70(S6K1), and p-RPS6.
- Tissue microarrays (TMAs) containing cores from HGPIN and PCa were utilized.
- Intratumoral heterogeneity of mTOR expression was quantified across multiple cores per patient.
Main Results:
- A decreasing trend in p-mTOR activity was observed from PIN to high-grade PCa.
- Significant intratumoral heterogeneity in IHC expression of mTOR components was noted within individual patients.
- A statistically significant correlation was found between p-mTOR, p-p70(S6K1), and p-RPS6 expression in each tissue core.
Conclusions:
- mTOR pathway inhibitors may represent a viable therapeutic strategy for HGPIN and PCa.
- Individual patient mTOR expression levels are crucial for determining the efficacy of mTOR inhibitor therapy.
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