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Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...

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Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
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Published on: March 14, 2014

Prostate cancer cell phenotypes based on AGR2 and CD10 expression.

Melissa E Ho1, Sue-Ing Quek, Lawrence D True

  • 1Department of Urology, University of Washington, Seattle, WA 98195-6100, USA.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|January 26, 2013
PubMed
Summary

Prostate cancer phenotypes based on AGR2 and CD10 expression predict patient outcomes. High AGR2 and low CD10 in metastases suggest a role in tumor spread, while the opposite is linked to poor primary tumor prognosis.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Prostate cancer progression and metastasis are complex processes.
  • Identifying biomarkers that correlate with clinical outcomes is crucial for effective treatment strategies.
  • Anterior gradient 2 (AGR2) and CD10 are proteins whose expression patterns may offer prognostic insights in prostate cancer.

Purpose of the Study:

  • To investigate the correlation between the expression patterns of AGR2 and CD10 in prostate cancer.
  • To determine if distinct phenotypes defined by AGR2 and CD10 expression correlate with clinical outcomes, including recurrence-free survival.
  • To explore the differential expression of AGR2 and CD10 in primary tumors versus metastatic sites.

Main Methods:

  • Immunophenotyping was used to distinguish four prostate cancer phenotypes based on AGR2 and CD10 expression levels: CD10(low)AGR2(high), CD10(high)AGR2(high), CD10(low)AGR2(low), and CD10(high)AGR2(low).
  • The correlation between these phenotypes and clinical outcomes, specifically recurrence-free survival, was analyzed.
  • Expression patterns of AGR2 and CD10 were examined in primary tumors, bone and soft tissue metastases, and xenografts.

Main Results:

  • AGR2-positive tumors were associated with longer recurrence-free survival, whereas CD10-positive tumors were linked to shorter recurrence-free survival.
  • In high-stage prostate cancer, the CD10(low)AGR2(high) phenotype showed a ninefold increase in recurrence-free survival compared to the CD10(high)AGR2(low) phenotype.
  • The CD10(high)AGR2(low) phenotype was prevalent in high-grade primary tumors, indicating poor prognosis. Conversely, metastases showed higher AGR2 and lower CD10 expression, with AGR2 readily detected in metastatic sites.

Conclusions:

  • The combination of AGR2 and CD10 expression defines distinct prostate cancer phenotypes with significant prognostic value.
  • The CD10(high)AGR2(low) phenotype in primary tumors predicts a poor clinical outcome.
  • A shift in expression, with higher AGR2 and lower CD10, observed in metastases suggests AGR2 may play a role in tumor cell dissemination and survival at distal sites, potentially acting protectively in primary tumors but promotively in metastasis.