Expression of cyclin E and cyclin-dependent kinase 2 correlates with metastasis and prognosis in colorectal carcinoma.

The expression of cyclin E and cyclin-dependent kinases 2 (CDK2) in metastatic foci, the relationship of their expression with some clinicopathologic characteristics, and the correlation of their expression with prognosis remain unclear. To examine the roles of their expression in the progression of colorectal carcinoma, 21 normal mucosa, 9 hyperplastic polyps, 58 adenomas, 17 adenocarcinoma in adenomas, 203 primary cancers, 21 lymph node metastases, and 10 hepatic metastases were immunohistochemically stained with anti-cyclin E, anti-CDK2, and anti-Ki67 antibodies. In the carcinogenic process, both cyclin E and CDK2 expressions increased significantly. From the primary to the lymph node-metastatic foci, cyclin E protein remained unchanged, but CDK2 increased significantly. From the primary to the liver-metastatic foci, cyclin E apparently decreased, and CDK2 was reduced almost to zero. In primary carcinomas, the reduction of cyclin E was significantly associated with large tumor size, mucinous type, venous invasion, deep infiltration, lymph nodal metastasis, peritoneal metastasis, advanced stage, and poor prognosis. Decreased CDK2 was obviously correlated with large tumor size, venous invasion, deep infiltration, hepatic metastasis, advanced stage, and poor prognosis. Increased cyclin E protein was related to elevated CDK2, which was further linked to higher Ki67. Thus, CDK2 overexpression could facilitate lymph node metastasis. The overexpression of cyclin E and CDK2 may mainly promote the progression of early cancer. Anti-cyclin E or anti-CDK2 chemotherapy should be targeted to the cancers with such overexpression.

Secondary myeloid/natural killer cell precursor acute leukemia following essential thrombocythemia.

The de novo leukemic transformation of essential thrombocythemia is a rare event, and usually associated with previous treatments. We describe a patient who received treatments with nitrosourea for long-standing essential thrombocythemia and subsequently developed extramedullary tumors, tentatively diagnosed as lymphoblastic lymphoma. Combination chemotherapy was initially successful, but relapsed with marked bone marrow involvement. Surface marker analysis revealed that the tumor cells had CD5, CD7, CD33, CD34, and CD56 antigens but lacked other T-cell, and B-cell markers. Immunogenotypical studies revealed germline configurations for both T-cell receptors and immunoglobulin genes. These clinical and phenotypical features are consistent with a myeloid/natural killer cell precursor leukemia, a recently proposed distinct clinical entity. To our knowledge, this is the first report of secondary leukemia of myeloid/ natural killer cell precursor origin, and suggest that myeloid/natural killer cell precursor might be a potent target of therapy-related leukemia.

Selective increase in expression of isoform PP1 gamma 1 of type-1 protein phosphatase in chondrosarcoma cells.

The expression of the two catalytic subunits of protein phosphatase (PP) type 1 PP1 gamma 1 and PP1 delta was examined in 4 cases of osteochondroma and 4 cases of enchondroma as a benign cartilaginous tumor, and 4 cases of chondrosarcoma as a malignant cartilaginous tumor using immunohistochemical analysis. The percentage of tumor cells stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma 1 were significantly higher in chondrosarcoma than in osteochondroma and enchondroma. Furthermore, chondrosarcoma showed markedly high S-phase fraction in the cell cycle of tumor cells, as compared to osteochondroma and enchondroma. These results suggest that PP1 gamma 1 is involved in the accelerated growth of malignant cells in chondrosarcoma.

Enhanced expression of catalytic subunit isoform PP1 gamma 1 of protein phosphatase type 1 in malignant fibrous histiocytoma.

The expression of the three catalytic subunits of protein phosphatase (PP) type 1 and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, was examined in malignant fibrous histiocytoma using immunohistochemical analysis. The percentage of cells stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma 1 was significantly higher in tumorous region than in non-tumorous region of malignant fibrous histiocytoma. Furthermore, tumorous region showed markedly high S-phase fraction in the cell cycle, as compared to non-tumorous region. These results suggest that PP1 gamma 1 is involved in the accelerated growth of tumor cells in malignant fibrous histiocytoma.

The importance of primary cytomegalovirus infection in childhood cancer.

Sixty-eight paediatric patients with malignant tumours or leukaemia were followed for signs of infection with human cytomegalovirus (HCMV) over 1 year. HCMV was isolated from 24 out of 68 patients at some point during the observation period; from urine in 14, from both urine and throat in 9 patients, and from throat alone in 1 patient. Previous antibody analysis indicated the presence of HCMV antibodies in 10 of the 24 virus-shedding patients, while 7 patients were seronegative and 7 undefined. Thus the incidence of reactivation appears to be higher than that of primary infection in these immunocompromised patients. The mean duration of virus shedding was 4.2 months in the primary infection group, 1.7 months in the reactivation group and 1.1 months in the undefined group. No difference in the incidence of HCMV-associated illness was observed between patients with leukaemia and those with malignant tumours. Clinical symptoms associated with HCMV infection (pneumonia (2), fever (6) and hepatitis (1)) were observed in all patients with primary infections and in only five patients with reactivated infection.

Radiologic-pathologic correlations of small lung nodules with special reference to peribronchiolar nodules.

A radiologic and pathologic correlation has been made of small lung nodules. At necropsy 100 excised lungs were fixed and slices from them radiographed. The radiographs were used to select individual nodules for histologic study. Nodules in bronchopneumonia, acinonodose tuberculosis, chronic bronchiolitis, and simple pneumoconiosis due to ferric dust were shown to be located around inflamed terminal or respiratory bronchioles. Intraacinar infiltration was usually diffuse, but when nodules were seen, they occurred in peripheral airspaces with no relation to bronchioles. Hematogenous metastases showed distinctly marginated nodules, some truly intraacinar. Although each type of nodule can appear as an "acinar" or "subacinar" image on chest radiographs, this radiologic-pathologic study shows that they differ significantly in their relation to the airway structures.