Loss of tumor suppressor gene expression in high-grade but not low-grade non-Hodgkin's lymphomas.
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.
Geradts
J
J
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 27599-7525, USA.
Andriko
J W
JW
Abbondanzo
S L
SL
D002453:Cell Cycle; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D015870:Gene Expression; D016161:Genes, Retinoblastoma / Q000235:genetics*; D019942:Genes, p16 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000737:chemistry; D008228:Lymphoma, Non-Hodgkin / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000032:analysis
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein