The present case illustrates the clinically aggressive nature of a primary retroperitoneal serous cystadenocarcinoma.

Background. Alterations of the p53 gene are involved in the development of diverse human malignancies, but their incidence and clinicopathologic features are still not well characterized for endometrial carcinoma. Methods. To investigate the clinicopathologic significance of p53, mutations and loss of heterozygosity (LOH) in endometrial carcinoma in 92 patients with this disease were examined. Results. Mutations of p53 were detected in 20 (22%) of the 92 patients with carcinoma, and LOH was detected in 23 (32%) of the 72 patients in whom heterozygosity of the gene was available. There was a significant correlation between the occurrence of mutation and LOH. Mutations and LOH were more frequent in patients with Grade 3 tumors than in those with Grades 1 and 2 tumors (P = 0.0498, P = 0.0051, respectively). Patients with LOH had a poorer postoperative survival than those without LOH (P = 0.0022, log‐rank test), and patients with both LOH and mutation showed the worst prognosis (P < 0.0001, log rank test). Loss of heterozygosity of the p53 gene showed a significant relation to prognosis that was independent of tumor stage, histologic grade, and muscular invasion. Conclusions. Mutation and LOH of the p53 gene are prognostic indicators in patients with endometrial carcinoma, suggesting that alterations of p53 may play an important role in the development of this cancer.

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An antigen histochemically localized in the nuclei and cytoplasmic granules of normal and leukemic human myeloid cells has been identified as myeloperoxidase (MPO; EC 1.11.1.7). The localization and amount of the enzyme was determined by using a murine monoclonal antibody designated H-43-5 raised against nuclear proteins derived from human promyelocytic HL-60 leukemia cells. The highest amount of nuclear MPO (3.5 ,.g per 106 nuclei) was found in granulocytes; less than half of this amount was detected in nuclei from HL-60 cells. Still lower levels were found in nuclei from monocytes and a series of human monomyelocytic leukemia cells. MPO from HL-60 cells was purified by immunoaffinity chromatography and fractionated into three components (forms I, II, and III) by CM-cellulose chromatography. Chromatography of these MPO forms on DNA-Sepharose columns confirmed that all three forms of MPO were tightly bound to DNA with apparent relative affinities in the order of form III > form II > form I. The affinity of MPO form III for DNA was sufficient to enable the formation and elution of DNA-MPO complexes during sizeexclusion chromatography at high ionic strength and neutral pH. This form of MPO was also able to shield DNA from strand scission induced by active oxygen species generated by xanthine oxidase acting aerobically on xanthine. These data suggest that intranuclear MPO may help to protect DNA against damage resulting from oxygen radicals produced during myeloid cell maturation and function.Oxygen metabolites are thought to play a central role in defending the body against microorganisms (1, 2) and protecting against cellular injury (3). In myeloid blood cells, including the human promyelocytic HL-60 leukemic cells, superoxide anions are generated during the maturation processes that lead to granulocyte or macrophage formation (4). However, production of excess oxygen radicals may cause DNA damage (5, 6) and cytotoxicity to these cells (7-9). Although possible mechanisms of protection against active oxygen species have been described (10, 11), little attention has been focused on the potential function of nuclear proteins in shielding chromatin and DNA from these oxygen species.In our laboratory, we are studying myeloid-specific nuclear antigens to determine their role in cell differentiation (12). One of these antigens was identified as myeloperoxidase (MPO; donor:hydrogen-peroxide oxidoreductase EC 1.11.1.7). This finding was unexpected because MPO was thought to be localized primarily in azurophil granules, cytoplasmic structures of phagocytic cells (13)(14)(15)(16), where its primary function is microbicidal.In this report, we describe the quantitation of intranuclear MPO in different cell types blocked at different stages of myeloid development. We have analyzed the degree of DNA-MPO interaction as well as inhibition by MPO of DNA strand breakage induced by oxygen radicals. Our results indicate that MPO is a DNA-binding nuclear protein that may protect the genetic material of myeloid cells from damag...

To determine whether p53 alterations, which are frequent in human breast cancers, are also common in rat mammary tumors, we examined 40 tumors from 24 rats treated with 7,12-dimethylbenz[a]anthracene (DMBA) and 34 tumors from 14 rats treated with N-nitroso-N-methylurea (NMU) (an N-nitroso compound). DMBA and NMU are known genotoxic mutagens. The entire coding regions of the p53 and Ha-ras genes were examined for mutations by polymerase chain reaction single-strand conformational polymorphism analysis and by direct sequencing. One of the 40 DMBA-induced mammary tumors had a p53 mutation, a single-base substitution (AGC-->GGC) at codon 307, resulting in an amino-acid change from Ser to Gly. No mutations were found in NMU-induced tumors. The incidence of Ha-ras gene mutation was 79% (27 of 34) at codon 12 in the NMU group and 23% (nine of 40) at codon 61 in the DMBA group. Thus, p53 mutation, in contrast to Ha-ras mutation, did not seem to be a prerequisite for carcinogenesis in chemically induced rat mammary tumors.