Ras oncogene expression of malignant melanoma and melanocytic nevus has been immunohistochemically analyzed using monoclonal antibodies which were generated against ras oncogene products (p21ras) derived from Harvey sarcoma virus. Freshly frozen tissues from 11 melanomas and 8 melanocytic nevi were examined by immunofluorescence method, and also, formalin-fixed and paraffin-embedded tissues from 26 melanomas and 24 melanocytic nevi by ABC method. There existed differences of p21ras expressions by the type of melanoma that nodular melanoma, epithelioid cell type melanoma, and deeply invaded melanoma revealed higher reactivity with anti-p21ras monoclonal antibody than the other types. The reactivity of melanomas were, thus, well correlated to the degree of malignancy of melanomas. In melanocytic nevi, dermally located nevus cells had relatively strong reactivity with anti-p21ras monoclonal antibody in contrast to junctional type nevi and the nevus cells located in the epidermis in compound type nevi which did not show the positive reaction. p21ras expressions in both melanomas and melanocytic nevi may represent a marker of the immature state of cells corresponding to early stages of the melanocyte evolution as well as the morphologic and enzymologic characteristics.

The inactivation of antioncogenes has been postulated to be important in the development of human malignancies. In 1986, a cDNA clone of the putative retinoblastoma antioncogene (Rb gene) has been isolated by molecular genetic approach. Recent work has shown that the neoplastic phenotype of retinoblastoma and osteosarcoma cells can be suppressed by the introduction of a cloned Rb gene. Interestingly, the product of the Rb gene has recently been shown to associate with the transforming proteins of DNA tumor viruses.

A 56-year-old female, who was diagnosed as CML in 1983 and had been well controlled with busulfan, was admitted to our hospital because of fever and iliac bone pain. Peripheral blood showed leukocytosis (WBC 70,000/microliters and bone marrow was normocellular with 53% leukemic cells, suggesting that she was in the blastic crisis. Chromosomal analysis of bone marrow cells at that time revealed t (9; 22; 12) and some additional abnormalities. The number of chromosomes ranged from 44 to 131 and the mode of chromosome number was 65. She was treated with combination regimen consisting of vincristine, 6-mercaptopurine and prednisolone and right iliac tumor was irradiated. Three months after admission, she died of DIC and pulmonary insufficiency due to leukemic infiltration.

Two cases of Ph1-negative chronic myelogenous leukemia (CML) are described, they were 66-year-old female and 73-year-old male. Both patients shared all of the following features: presence of anemia, thrombocytopenia and leukocytosis with every stage of neutrophilic differentiation, hypercellular bone marrow with hyperplasia of the degranulated neutrophilic series, diminished neutrophilic alkaline phosphatase, elevated serum lysozyme and vitamin B12 level, mosaic pattern of trisomy 8 and normal karyotypes in chromosome analysis, and markedly increased number of CFU-GM. In addition, bcr rearrangement by Southern blot hybridization was not demonstrated in these patients. The diagnosis of chronic myelomonocytic leukemia was not verified, however, because of the absence of monocytosis in peripheral blood. The existence of so-called Ph1-negative CML like these two cases as a diagnostic entity must be further studied.

Nineteen patients with typical osteosarcoma were studied for evidence of association with human leukocyte antigen (HLA) phenotypes. HLA-A11 was detected in nine of 19 patients (47.4%) compared with 16.9% of 235 controls (chi 2 " 10.861, p less than 0.001), which yielded an odds ratio of 4.523. The positive rate of HLA-A11 was significantly increased in the patients. Interestingly, five of seven patients with poor prognosis had HLA-A11, compared with two of nine disease-free patients, 18 months after the initial treatment. These data suggest that major histocompatibility complex (MHC)-linked genes determines susceptibility to the occurrence of osteosarcoma and its prognosis.

Thirteen colorectal cancer cell lines were established from 120 fresh colon cancer specimens. Expression of colon cancer-related antigens and blood group-related antigens on these cell lines were evaluated by Mixed Hemadsorption test (MHA) and Immune Adherence test (IA). The results were compared with the results of immunohistological analysis of the antigen expression in sections of the original tissues, and deletions of several blood group-related antigens in cell lines were observed. Colon cancer cell line HT-29, cultured in different lots of FCS or in different types of serum-free medium showed various antigen expression, suggesting the effect of culture medium on phenotypic expression. In glucose-free medium, HT-29 cells showed the characteristic "dome formation" which is typical of enterocytic differentiation forming brush borders in such cells. HT-29 cells cultured on bovine corneal endothelial extracellular matrix (BCE-ECM) coated plates showed similar enterocytic changes under phase-contrast microscope. Also, irradiated HT-29 cells cultured under 8-Azaguanine containing medium retained their strong resistance to 8-Azaguanine. These results suggest that these cancer cell lines might alter their phenotype, morphology, differentiation, growth pattern and drug sensitivity depending on the culture environment.

In 1982, the French-American-British (FAB) Cooperative Group proposed the myelodysplastic syndrome (MDS), which comprised a group of heterogeneous hematologic disorders characterized by various degrees of cytopenias and a possibility of leukemic transformation. And chromosome findings of bone marrow cells from patients with this syndrome are reported to have one of the greatest prognostic significance. In our chromosome study of 97 patients with MDS, we found clonally abnormal karyotypes in 61 patients (63%), including the whole chromosome or partial loss of long arm of chromosome 7 (-7/7q-) in 18 patients and a partial loss of chromosome 5 (5q-) in 14 patients. Among these 97 patients, 26 received cytostatic chemotherapy (small dose of cytarabine; 23 patients, small dose of behenoyl Ara-C; 2, and intensive combined chemotherapy; 1) as well as supportive care. Among these 26 treated cases, pretreatment hematological characteristics or FAB subclassifications were not associated with response to chemotherapy. In contrast, only one of 9 patients with -7/7q- and/or 5q- achieved a partial remission, while 5 of 8 patients with other abnormal karyotypes and 4 of 9 patients with normal karyotype achieved a complete (4 patients) or a partial remission. In conclusion, pretreatment cytogenetic findings can predict the potential responders to this chemotherapy, and may be one of the most important factors in the selection of the treatment for this ill-managed syndrome.

We attempted to elucidate the diagnosis and treatment in 11 patients with hereditary medullary thyroid carcinoma which were inherited as autosomal dominant traits. The oncogens are thought to be supported by the two-mutational event theory; the C cell hyperplasia, the first step, is the expression of the genetic mutation, which requires a subsequent somatic mutation to transform the initially mutated cell into a cancer cell. The C-cell hyperplasia was thought to be precancer state. The definitive diagnosis was established by measurement of calcitonin and CEA levels in sera. In patients with normal levels of calcitonin and CEA, the provocative test (Ca-gluconate plus pentagastrin) was useful such as in pt. no. 11,K.N.). The principle of surgery is total thyroidectomy because of multicentric occurrence in both lobes. Two patients (pt nos. 10, 11) with normal postoperative levels of provocative test underwent total thyroidectomy.