LOCALIZATION OF THE CELL-PROLIFERATION AND APOPTOSIS-ASSOCIATED CAS PROTEIN IN LYMPHOID NEOPLASMS

We have evaluated the expression and distribution of the cellular apop tosis susceptibility (CAS) protein in normal lymphoid tissue and malig nant lymphomas. CAS protein, the product of the CAS gene, is associate d with microtubules and the mitotic spindle. Immunohistochemistry with an antibody to CAS shows many CAS-positive cells in normal tonsils. T he majority of strongly CAS-positive cells were localized to the dark zone of the follicles, whereas the mantle zone and interfollicular are as were essentially negative. Double staining for CAS and Ki-67 reveal ed co-expression of the two proliferation markers in approximately 85 to 90% of the CAS-positive cells. Different subtypes of lymphomas exhi bited varying patterns of CAS expression. Low-grade non-Hodgkin's lymp homa generally revealed weak staining with CAS, with 10 to 60% of all cells being positive. In contrast, highly malignant non-Hodgkin's lymp homa and malignant cells of Hodgkin's disease displayed very strong CA S positivity, with staining pattern of CAS and Ki-67 was superimposabl e within a particular lymphoma subtype. However, in all lymphomas we o bserved a significant fraction of CAS-positive normal and malignant ly mphocytes that were Ki-67 negative, probably because they were momenta rily noncycling cells. We conclude that a high expression of CAS corre lates with proliferation of normal and malignant lymphoid cells. The f act that detection of CAS protein identifies a higher portion of proli ferating and malignant cells than Ki-67 warrants further evaluation of CAS protein as a marker with a diagnostic potential.