Summary Traditional clinicopathological features do not predict which patients will develop chemotherapy resistance. The TP53 gene is frequently altered in ovarian cancer but its prognostic implications are controversial. Little is known on the impact of TP53-downstream genes on prognosis. Using molecular and immunohistochemical analyses we examined TP53 and its downstream genes p21, BAX and BCL-2 in ovarian tumour tissues and have evaluated the results in relation to clinico-pathological parameters, clinical outcome and response to platinum-based chemotherapy. Associations of tested factors and patient and tumour characteristics were studied by Spearman rank correlation and Pearsons χ 2 test. The Cox proportional hazard model was used for univariate and multivariate analysis. The associations of tested factors with response was tested using logistic regression analysis. TP53 mutation, p21 and BCL-2 expression were not associated with increased rates of progression and death. Expression of TP53 was associated with a shorter overall survival only (relative hazard rate [RHR] 2.01, P = 0.03). Interestingly, when combining TP53 mutation and expression data, this resulted in an increased association with overall survival (P = 0.008). BAX expression was found to be associated with both progression-free (RHR 0.44, P = 0.05) and overall survival (RHR 0.42, P = 0.03). Those patients who simultaneously expressed BAX and BCL-2 had a longer progression-free and overall survival compared to patients whose tumours did not express BCL-2 (P = 0.05 and 0.015 respectively). No relations were observed between tested factors and response to platinum-based chemotherapy. We conclude that BAX expression may represent a prognostic indicator for patients with ovarian cancer and that the combined evaluation of BAX and BCL-2 may provide additional prognostic significance.

SUMMARY:Chromosomal information on germ cell tumors of the infantile testis, ie, teratomas and yolk sac tumors, is limited and controversial. We studied two teratomas and four yolk sac tumors using comparative genomic hybridization (CGH) and in situ hybridization. No chromosomal anomalies were found in the teratomas by any of the methods, not even after CGH on microdissected tumor cells. All yolk sac tumors showed aneuploidy, loss of parts of 4q and 6q, and gain of parts of 20q. Underrepresentation of parts of 8q and overrepresentation of parts of 3p, 9q, 12p, 17, 19q, and 22 were detected in most cases. In addition, one recurrent yolk sac tumor after a sacral teratoma was studied, showing a highly similar pattern of imbalances. While CGH demonstrated loss of 1p36 in one testicular yolk sac tumor, in situ hybridization revealed loss of this region in all yolk sac tumors. High-level amplification of the 12q13-q14 region was found in one yolk sac tumor. MDM2, of which the encoding gene maps to this chromosomal region, was found in all cases using immunohistochemistry, whereas no p53 could be detected. Accordingly, no mutations within exons 5 to 8 of the p53 gene were observed. These data prove the absence of gross chromosomal aberrations in teratomas of the infantile testis and show a characteristic pattern of gains and losses in the yolk sac tumors. Besides confirmation of previously found anomalies, recurrent losses of 1p21-31 and 4q23-33 and gains of 9q34 and 12p12-13 have not been reported before. While genetic inactivation of p53 seems unimportant in the pathogenesis of these tumors, biochemical inactivation by MDM2 might be involved. These data support the existence of three entities of germ cell tumors of the human testis: teratomas and yolk sac tumors of infants, seminomas and nonseminomas of adolescents and young adults, and spermatocytic seminomas of the elderly, each with its own specific pathogenesis. (Lab Invest 2000, 80:1055-1064.

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Genes homologous to the auxin-inducible Ntl03 glutathione S-transferase (GST) gene of tobacco, were isolated from a genomic library of Arabidopsis thaliana. We isolated a 2 clone containing an auxininducible gene, AtlO3-1a, and part of a constitutively expressed gene, AtlO3-1b. The coding regions of the Arabidopsis genes were highly homologous to each other and to the coding region of the tobacco gene but distinct from the GST genes that have been isolated from arabidopsis thusfar. Overexpression of a cDNA clone in Escherichia coli revealed that the AT103-1A protein had GST activity.

Cyclins, cyclin-dependent kinases (CDKs) and cyclindependent kinase inhibitors (CKIs) play a key role in cell cycle control. To achieve an orderly progression through the cell cycle, different cyclin -CDK complexes need to be activated and deactivated at appropriate times. Cyclin D-CDK4 is one of the complexes that promotes cell passage through the G1 phase of the cell cycle. It increases the phosphorylation state of the retinoblastoma protein which then releases transcription factors (e.g. E2F) essential for progression into the S-phase (reviewed by Sherr, 1993;Hartwell and Kastan, 1994;Hunter and pines, 1994 al., 1994).Another negative regulator of cyclin D-CDK4/6 activity is the p16 protein, encoded by the CDKN2 (MTSIpl6in'k4/ CDK4I) gene (Serrano et al., 1993;Nobori et al., 1994 (1979) classification the primary and metastatic carcinomas were subtyped into serous (n = 14 primary, n = 5 metastatic), mucinous (n = 4), endometroid (n = 7), clear cell (n = 2), mixed (n = 3), poorly differentiated (n = 1) and unknown (n = 1). To estimate the percentage of tumour cells, frozen sections were made from a representative part of each tumour and stained with haematoxylin and eosin. The