Using the poylmerase chain reaction and single‐strand conformation polymorphism analysis, p53 gene mutations were examined in 24 cases of ovarian tumor including 14 ovarian carcinomas and 2 borderline cases of common epithelial type, 7 germ cell tumors, and one stromal tumor. Abnormal bands indicating mutations were detected in 12 (50%) of the cases examined, being present most frequently in common “epithelial” ovarian carcinoma (71%, 10/14). One case each of squamous cell carcinoma originating in a dermoid cyst and anaplastic dysgerminoma were positive for mutation. Direct sequencing confirmed 12 mutations and revealed G→A and G→C nucleotide changes in 5 and 3 cases (42% and 25%), respectively. The mutation was localized at the CpG site of the gene in 3 cases. Immunohistochemical examination of p53 protein in 21 cases and DNA flow‐cytometrical analysis in 17 cases were also performed. Nuclear accumulation of the p53 protein and DNA aneuploidy pattern were detected in 11 (52%) and 9 (53%) cases, respectively. These were significantly correlated with p53 gene mutation (P<0.01 and P<0.05, respectively; Fisher's exact test). Neither mutation of the p53 gene, nuclear accumulation of p53 protein nor DNA aneuploidy was detected in borderline cases of common “epithelial” type, typical dysgerminoma and immature teratoma. These results suggest that p53 gene mutation, nuclear accumulation of the protein and the DNA aneuploidy pattern are events occurring almost simultaneously in the progression of ovarian tumors, and that p53 abnormalities seem to be correlated with a high grade of malignancy.

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Background. The overexpression of c‐erbB‐2 protein is a prognostic marker in patients with breast cancer. Alteration of the c‐erbB‐2 oncogene in development of adenocarcinoma of the uterine cervix, an unfavorable gynecologic neoplasm, is unknown. Methods. To clarify the role of the c‐erbB‐2 oncogene in adenocarcinoma of the uterine cervix, formalin‐fixed, paraffin‐embedded tissue sections from 44 cases of cervical adenocarcinoma were immunohistochemically examined for expression of c‐erbB‐2 protein and for c‐erbB‐2 gene amplification in DNA by slot blot‐hybridization analysis. Results. The expression of c‐erbB‐2 protein was detected in 34 cases (77%). Strong expression on cell membranes was detected in 11 cases (25%). Most cases with strong membrane expression of c‐erbB‐2 protein also showed amplification of the c‐erbB‐2 gene by slot blot‐hybridization. Expression of the protein on cell membranes was more often seen at clinical Stage II or III (9 of 23 [39%]) than at Stage 0 or I (2 of 21 [9%]) (P < 0.05, Fisher's exact test). Expression of the c‐erbB‐2 protein was also associated with poorer prognosis of patients with cervical adenocarcinoma by comparison of survival curves (P < 0.005) and by the Cox regression model analysis. Conclusions. Overexpression of c‐erbB‐2 protein is associated with amplification of c‐erbB‐2 gene and frequently occurred in cervical adenocarcinomas of the patients with poor prognoses.

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.

In order to understand the trigger mechanism of slow‐moving landslides occurring in the early cold season from late autumn to winter, we investigated the effect of temperature on the shear strength of slip surface soils. Displacement‐controlled and shear stress‐controlled box shear experiments were performed on undisturbed slip zone soils under residual strength conditions. Test results conducted at temperatures from 9 to 25°C showed remarkable shear strength reductions with decreasing temperature. Creep‐like slow shear displacements were induced by a decrease in temperature. These temperature‐dependent shear behaviors are attributed to the rheological properties of hydrous smectite that dominantly compose the soil material along the failure surface. Our experimental results imply that ground temperature conditions influence slope instability, especially for shallow landslides occurring in smectite‐bearing rock areas.