Paraffin-embedded surgical biopsy material from 17 Hürthle cell tumors of the thyroid was examined for DNA content by flow cytometry to assess the diagnostic and prognostic utility of ploidy determinations in these rare tumors. Both adenomas (11 cases) and carcinomas (6 cases) were studied. As a control for methods, ten randomly selected normal autopsy thyroids were analyzed, all of which demonstrated normal diploid DNA content. Among the Hürthle cell tumors, however, aneuploid peaks were present in six adenomas (55%) and in four carcinomas (67%). Similarly, polyploid DNA peaks in the absence of other aneuploid peaks were present in two adenomas and two carcinomas (18% and 33%, respectively). These findings demonstrate the limited value of aneuploidy or polyploidy as diagnostic features for malignancy in Hürthle cell tumors of the thyroid. As for prognosis, there does not appear to be any unfavorable prognostic significance for abnormal DNA content in histologically benign Hürthle cell tumors treated by surgical excision because no metastases or recurrences occurred in this group at a mean disease-free follow-up of 50 +/- 19 months for six aneuploid lesions and 19 +/- 7 months for two polyploid adenomas. Preliminary data suggest that aneuploidy may, however, have an important prognostic value for histologically defined Hürthle cell carcinomas, because the only patient to die from the tumor in this series had an aneuploid Hürthle carcinoma. Thus, the authors' data indicate that the diagnostic utility of DNA content in Hürthle cell tumors is extremely limited and that there does not appear to be any negative prognostic significance for aneuploidy in histologically defined Hürthle cell adenomas.
A monoclonal antibody, designated BM-1, which is reactive in B5 formalin-fixed, paraffin-embedded tissues, has been generated against a cytoplasmic and nuclear antigen expressed in human myeloid precursor cells and derived leukemias. Using the avidin-biotin-complex immunoperoxidase procedure, BM-1 was found to stain selectively myeloid precursor cells in normal bone marrow and mature granulocytes in the blood. In a screen of 26 normal adult and fetal human organs fixed in B5 formalin, BM-1 was negative in all nonhematopoietic tissues with the exception of tissue granulocytes and scattered cells in the peripheral cortex of the thymus. Likewise a screen of 30 solid tumor cell lines including a spectrum of carcinomas, sarcomas, and neural-derived tumors was negative. BM-1 was also negative with 21 T and B cell lymphomas and 11 Hodgkin's disease tumors. A preliminary study of tumors of the hematopoietic system revealed that BM-1 was reactive with M2 and M3 acute myelogenous leukemias (AML), chronic myelogenous leukemias (CML) and myelomonocytic leukemias, and granulocytic sarcomas. M1, M4, M5, and M6 AML clot preparations were negative in this study, indicating that BM-1 may have a role in the histopathologic diagnosis of myelogenous leukemia. Myeloid leukemic cell lines HL-60, ML-2, KG1, and TPH-1-O showed BM-1 nuclear and/or cytoplasmic reactivity in a subpopulation of cells, but erythroid and lymphoid leukemias and all lymphoma cell lines were negative. Immunoperoxidase studies of a panel of fetal tissues showed BM-1 positive cells in the peripheral cortex of the thymus and portal myelopoietic regions of the liver at 18 weeks gestation. Finally, DNA-cellulose and solid phase radioimmunoassay (RIA) techniques developed in our laboratory demonstrate that the BM-1 antigenic domain is reactive only after binding to eukaryotic but not prokaryotic single- or double-stranded DNA. Immunoblot techniques using a DNA-cellulose purified protein sample revealed that BM-1 recognizes a 183 kD protein. These studies indicate that BM-1 is recognizing a myeloid-specific antigen that, because of its DNA binding characteristics, may have an important role in the differentiation of myeloid cells at the molecular level.
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