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Loss of tumor suppressor gene expression in high-grade but not low-grade non-Hodgkin's lymphomas
J Geradts1, J W Andriko, S L Abbondanzo
1Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 27599-7525, USA.
Abstract:
The products of the MTS1/CDKN2 and retinoblastoma (RB) tumor suppressor genes, p16 and pRB, act as agonists in controlling the late G1 cell cycle checkpoint. Inactivation of either gene occurs in a wide range of human malignant neoplasms. Data on the expression of both genes in the same set of malignant lymphoid neoplasms are scarce. We studied the p16/pRB pathway in low-grade and high-grade non-Hodgkin's lymphomas, using immunohistochemical techniques. Paraffin sections of 9 reactive lymph nodes and 43 low-grade and 60 high-grade malignant lymphomas were reacted with antibodies against pRB and p16. All benign lymph nodes showed a normal pattern of RB and MTS1/CDKN2 expression. Of 101 evaluable lymphomas, only a single high-grade tumor displayed loss of RB reactivity. Loss of p16 was identified in 14 of 55 evaluable high-grade lymphomas but not in any of the low-grade lesions. All but 3 of the RB- and p16-negative cases were diffuse large cell lymphomas, for an abnormality rate of 55% in this category. While loss of RB function was a rare event in human lymphomagenesis, p16 was absent in some 25% of high-grade non-Hodgkin's lymphomas; diffuse large cell lymphomas were the primary target of tumor suppressor gene inactivation.
Insights
Loss of the p16 tumor suppressor gene is common in high-grade non-Hodgkin's lymphomas, particularly diffuse large cell lymphomas. RB gene inactivation is rare in these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cell Cycle Regulation
Background:
- The MTS1/CDKN2 (p16) and retinoblastoma (RB) tumor suppressor genes are crucial for regulating the G1 cell cycle checkpoint.
- Inactivation of these genes is frequent in various human cancers, but their co-expression in lymphoid neoplasms is understudied.
- Understanding p16 and pRB pathway alterations is vital for comprehending lymphomagenesis.
Purpose of the Study:
- To investigate the expression patterns of p16 and pRB in low-grade and high-grade non-Hodgkin's lymphomas.
- To determine the frequency and specific lymphoma subtypes affected by alterations in the p16/pRB pathway.
Main Methods:
- Immunohistochemical analysis of pRB and p16 expression was performed on paraffin-embedded tissue sections.
- Samples included 9 reactive lymph nodes, 43 low-grade, and 60 high-grade non-Hodgkin's lymphomas.
Main Results:
- Normal pRB and MTS1/CDKN2 expression was observed in all benign lymph nodes.
- Loss of RB reactivity was rare, occurring in only one high-grade lymphoma.
- Loss of p16 was detected in 14 of 55 high-grade lymphomas (approximately 25%), but not in low-grade lymphomas. Diffuse large cell lymphomas showed a 55% abnormality rate for p16/RB inactivation.
Conclusions:
- Alterations in the p16/pRB pathway, particularly p16 loss, are significantly associated with high-grade non-Hodgkin's lymphomas.
- Diffuse large cell lymphomas are the predominant subtype affected by tumor suppressor gene inactivation within this pathway.
- RB gene inactivation is infrequent in lymphomagenesis, while p16 inactivation is a notable event in aggressive lymphomas.
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