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Published on: September 13, 2019
Loss of RB and MTS1/CDKN2 (p16) expression in human sarcomas
1Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill 27599-7525, USA.
Abstract:
The product of the MTS1/CDKN2 gene (p16) and the retinoblastoma protein (pRB) inhibit cell cycle progression at the late G1 checkpoint. The absence of functional p16 or pRB has been identified in a variety of human tumors but has not been well studied in mesenchymal neoplasia. Using an immunohistochemical approach, the authors identified abnormal expression of either p16 or RB in 16 and 14 of 59 sarcomas, respectively, for an overall abnormality rate of 51%. Specific rates of abnormality varied by histological subtype, with leiomyosarcomas most commonly affected by loss of either tumor-suppressor gene product. There was no significant correlation between p16 or RB expression and overall grade, mitotic grade, or tumor progression for sarcomas. In contrast, no fibromatoses and other spindle cell neoplasms of low malignant potential displayed abnormal p16 expression, and only 4 of 23 cases showed loss of pRB expression. These data show that aberrant expression of p16/pRB is one of the most common molecular derangements in sarcomagenesis.
Insights
Abnormal expression of p16 and retinoblastoma protein (pRB) is common in sarcomas, affecting over half of tumors. This suggests their aberrant expression is a key event in sarcoma development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p16/CDKN2 and pRB proteins are critical regulators of the cell cycle, inhibiting progression at the G1 checkpoint.
- Loss of p16 or pRB function is implicated in various human cancers.
- Their role in mesenchymal neoplasia, particularly sarcomas, is less understood.
Purpose of the Study:
- To investigate the frequency and patterns of aberrant p16 and pRB expression in a cohort of human sarcomas.
- To determine if p16/pRB abnormalities correlate with histological subtype, grade, or tumor progression.
Main Methods:
- Immunohistochemistry was employed to assess the expression of p16 and pRB proteins in 59 sarcoma samples.
- Expression levels were analyzed in relation to histological subtypes and clinicopathological features.
Main Results:
- Abnormal expression of p16 or pRB was detected in 51% of sarcomas (30 out of 59 cases).
- Leiomyosarcomas showed the highest rates of abnormality for both proteins.
- No significant correlation was found between p16/pRB expression and tumor grade or progression.
- Low-grade spindle cell neoplasms rarely showed p16/pRB abnormalities.
Conclusions:
- Aberrant p16/pRB expression is a frequent molecular alteration in sarcomagenesis.
- These tumor suppressor genes are significantly implicated in the development of sarcomas, especially leiomyosarcomas.
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