Alkaline phosphatase and gamma glutamyltranspeptidase in human lymphomas.

Alkaline phosphatase (AP) and gamma glutamyltranspeptidase (GGT) were studied in normal lymphoid cells and in 28 cases of human lymphomas (23 of non-Hodgkin's and 5 of Hodgkin's disease). The expression of AP was enhanced in several samples with a high proportion of mature B cells, particularly in centroblastic-centrocytic lymphoma, whereas tissues mainly composed of T cells always showed low levels of this enzyme. GGT levels were high in thymus, as well as in centroblastic-centrocytic lymphoma and other NHL, thus demonstrating no restriction to a particular cell lineage. Some B-cell neoplasms with cellular origin different from that of centroblastic-centrocytic lymphoma, such as chronic lymphocytic leukemia and centrocytic lymphoma, had low levels of both enzymes. The role of investigation with specific antibodies against these two enzymatic activities in the physiology of lymphoma cell membrane is discussed.

Relation between enzymatic activities and the degree of malignancy of human lymphomas.

The relationship between the intracellular levels of DNA polymerase alpha (DP-alpha), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) and the degree of malignancy of human lymphomas was investigated. Twelve non-neoplastic lymph nodes and 88 malignant lymphomas were examined. For non-Hodgkin's lymphomas (NHL) the low or high grade of malignancy was established according to three classifications: the Rappaport, the Kiel and the Working Formulation for Clinical Usage, with the latter also recognizing an intermediate grade group. Non-neoplastic lymph nodes had significantly lower levels of all the three enzymes than those found in high-grade malignant NHL (the P value ranged from less than 0.02 to less than 0.001). Hodgkin's disease, a slowly evolving neoplasia, showed lower levels of DP-alpha (P less than 0.001) and ADA (P less than 0.001), but not of LDH, than high-grade NHL. Among NHL, whatever classification was used, the low-grade malignant lymphomas had significantly lower levels than the high-grade ones for all the three enzymes (P less than 0.005 or P less than 0.001). The intermediate-grade group of the Working Formulation differed from the high-grade group for DP-alpha (P less than 0.01) and ADA (P less than 0.02) but not for LDH. It differed from the low-grade group only for ADA (P less than 0.005). Lymphoblastic and Burkitt's lymphomas were the groups with the highest levels of the three enzymes. Among low-grade lymphomas very low values were found in the histological entities defined as DLWD in the Rappaport classification, CLL and lymphoplasmacytoid immunocytoma in the Kiel classification and small lymphocytic (group A) in the WF. The levels of all enzymes in these histotypes were always significantly different from the other low-grade histotypes, and from the intermediate-grade ones of the WF. In the Kiel classification polymorphous lymphoplasmacytoid lymphoma, recently recognized as a group with a quite aggressive clinical course, was characterized by high levels of all three enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine deaminase and terminal deoxynucleotidyl transferase in human lymphomas: an aid to the diagnosis and subclassification of lymphoblastic lymphomas.

Adenosine deaminase (ADA) and terminal deoxynucleotidyl transferase (TdT) activities were determined on 97 biopsy specimens obtained from patients with non-neoplastic diseases (12 cases), Hodgkin (30 cases), and non-Hodgkin lymphomas (55 cases). Thirty additional cases were tested only for TdT. TdT was positive in 10 out of 13 lymphoblastic lymphomas (LL) examined and negative in all the other specimens, including the ten cases of the immunoblastic type. Levels of ADA above 350 U/mg of protein were found in 10 out of 12 LL tested, but not in any other specimen. The 3 TdT- LL had high contents of ADA. Therefore, all LL can be detected using both ADA and TdT markers. The 3 TdT- LL had a heterogeneous phenotype and their possible origin is discussed in view of the possibility that they constitute a rare entity distinct from the more common TdT+ LL. Very low levels of ADA (below 100 U/mg of protein) were found in chronic lymphocytic leukemia and immunocytoma, and in Burkitt's lymphoma. In other B-cell non-Hodgkin lymphomas, intermediate values between 100 and 350 U were often found, and this finding could be relevant to the different cellular origin of the various B-cell neoplasias. We conclude that ADA distribution is solid lymphoid tumors reflects the cellular origin of these neoplasias. Adenosine deaminase alone and in combination with TdT can be useful in the diagnosis and classification of childhood lymphomas in which the immature hystotypes predominate.

Multienzymatic analyses of human malignant lymphomas. Correlation of enzymatic data with pathologic and ultrastructural findings in Burkitt's and lymphoblastic lymphomas.

Enzyme activity measurements are of great relevance to the classification and biochemical characterization of the various types of leukemias, but they have been much less studied in solid lymphoid tumors. The authors report investigations in human lymphomas. The levels of the following enzymes were determined: terminal deoxynucleotidyl transferase (TdT), deoxyribonucleic acid polymerase alpha (DP alpha), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), thymidine and uridine kinases (TK and UK, respectively), and thymidine phosphorylase (ThPh). Moreover, cytochemical investigations were done in the group of Burkitt's lymphoma (BL) and lymphoblastic lymphoma (LL), and ultrastructural studies were performed in seven of the nine LL of this series. These results were obtained: (1) TdT (90 cases) was highly specific for LL; eight of nine LL were positive, and all other histologic types were negative; the only TdT-, acid esterase (AcE) positive, nonconvoluted LL was probably related to TdT- normal medullary thymocytes, and had an unfavorable clinical course with resistance to a vincristine-and-prednisone-including treatment; (2) ADA (61 cases) could distinguish clearly between the high levels of LL and the low levels found in any other group of lymphomas; among LL, the highest values were found in T-cell-derived neoplasias, and the lowest value in a periodic acid-Schiff (PAS) positive, acid phosphatase negative case that showed the presence of large nucleoli at the ultrastructural analysis, a finding that is unusual for LL and possibly related to a more immature differentiation stage; (3) PNP (39 cases) values alone were not clinically relevant, but together with ADA levels, a subset of T-LL with high ADA:PNP ratio could be selected among LL; (4) DP alpha (61 cases), and TK and UK (37 cases) were found in concentrations reflecting the malignancy of the non-Hodgkin's lymphoma, and were more elevated in the high-grade malignant lymphomas; (5) ThPh (34 cases) was always elevated in Hodgkin's disease, but low in Burkitt's lymphoma and LL; thus, they had a high TK:ThPh ratio that could be useful in predicting clinical response to thymidine treatment. The authors think that taken together, multiple enzyme determinations could be useful in the characterization of human lymphomas.

Poly(A) polymerase distribution in normal and malignant lymphoid cells.

The incorporation of ATP on poly(A) primers catalyzed by poly(A) polymerase was investigated in normal and neoplastic lymphoid cells from animal and human sources. High levels of the enzyme were found in mouse thymus, in chicken bursa and thymus, as well as in neoplastic cells from patients affected by lymphoblastic and Burkitt's lymphomas. Low or very low quantities were found in peripheral blood lymphocytes, chronic lymphocytic leukemia cells, normal lymph nodes and solid lymphoid tissues of Hodgkin's disease. In general, the enzymatic content of neoplastic lymphoid cells reflected those of their normal counterpart. No effect of fasting or cortisone treatment on poly(A) polymerase in mouse spleen, thymus or liver was found. No particular relationships with B, T or non-T, non-B lineages were observed, but some relationship with DNA polymerase alpha was found. Therefore, it may be that poly(A) polymerase levels are related to the proliferative activity of the cellular populations.

Lactate dehydrogenase levels in cellular extracts of human malignant lymphomas.

Serum lactate dehydrogenase (LDH) levels have been claimed as an independent prognostic factor in non-Hodgkin's lymphomas (NHL). In the present study, the intracellular and serum LDH levels in Hodgkin's (HD) and NHL were investigated. We found that among NHL, the histologic types of high-grade malignancy (lymphoblastic, immunoblastic and centroblastic), according to the Kiel classification, have a significantly higher intracellular (p less than 0.01) and serum (p less than 0.05) content of this enzyme than those of low-grade malignancy. This finding could explain in part the relation between high serum LDH levels and poor prognosis. It is also possible that the stage of the disease at the moment of the serum determination could be related to the serum LDH level, because a large tumor burden is likely to release more enzyme than a smaller one. However, we could not test this hypothesis because in our series there was ony one NHL patient with stage I or II. Serum LDH level could be a predictor of prognosis in NHL because of its relationship with more malignant histological types, and possibly with more advanced diseases.