G. Stammler

Prognostic value of basic fibroblast growth factor and its receptor (FGFR-1) in patients with non-small cell lung carcinomas

Tumour specimens of 206 patients with untreated non-small cell lung carcinomas (NSCLC) were analysed immunohistochemically for the expression of the basic fibroblast growth factor (bFGF) and for its receptor (FGFR-1, Flg). Seventy of the tumours showed weak expression, 109 moderate and 27 high expression of bFGF. Thirty-eight tumours had low expression of FGFR-1, 116 had moderate and 52 cases high expression. Patients with high FGFR-1 expression had significantly shorter survival times than patients with weak or moderate expressions (P < 0.05), but there was no significant correlation between bFGF expression and patient survival. The results of the multivariate analysis demonstrated that FGFR-1 in the presence of stage is not an independent prognostic factor.

Prognostic implications of cyclins (D1, E, A), cyclin-dependent kinases (CDK2, CDK4) and tumor-suppressor genes (pRb, p16INK4A) in childhood acute lymphoblastic leukemia

Immunohistochemistry was used to analyze samples of 40 newly diagnosed childhood acute lymphoblastic leukemias (ALL) for their expression of cyclins (D1, E, A), cyclin‐dependent kinases (cdk2, cdk4) and tumor‐suppressor genes (pRb, p16INK4A), in order to discover whether or not the expression of these various proteins may be of prognostic relevance for the survival of children with ALL. Patients with ALL who were strongly positive for cyclin D1 had a lower probability of remaining in first continuous remission than ALL patients who were negative or weakly positive for this trait. There was also a significant correlation between expression of cyclin D1 and frequency of recurrence. For cyclin E and cyclin A, in contrast, there was no difference in the duration of relapse‐free‐intervals or the frequency of recurrence in patients. Children with cdk4‐positive ALL had a lower probability of remaining in first continuous remission than children with cdk4‐negative ALL. No prognostic relevance was found for cdk2. Patients with ALL who expressed pRb had a higher probability and patients who expressed p16 a lower probability of remaining in first continuous remission, but the results were not statistically significant. This investigation demonstrated that cyclin D1 and cdk4 were the most important prognostic factors for children with ALL, and that the combination of them showed the strongest prognostic relevance. Int. J. Cancer 74:508–512, 1997.

Expression of resistance-related proteins in tumoral and peritumoral tissues of patients with lung cancer.

Twenty tumoral and peritumoral tissues from patients with lung cancer were analyzed immunohistochemically for the drug resistance-related proteins P-glycoprotein (P-170), topoisomerase II (Topo-II), glutathione S-transferase-pi (GST-pi), metallothionein (MT), heat shock protein-70 (HSP-70) and the putative regulators of resistance (ErbB1, Fos and Jun). Protein expression of Topo-II, GST-pi, MT, HSP-70, ErbB1, Fos and Jun was elevated in tumor tissue in comparison to normal tissue. The different expression of the proteins between tumoral and normal tissues was statistically significant for Topo-II (P = 0.05), MT (P = 0.03), and HSP-70 (P = 0.01), whereas ErbB1 showed a borderline significance. The expression of the proteins was frequently increased in smokers in comparison to non-smokers. In general, the increase of the proteins of smokers corresponded in tumoral and non-tumoral tissue. Different expression was only found with MT and HSP-70 which were higher in tissues of smokers.

Heat shock (hsp70) and resistance proteins in non-small cell lung carcinomas

The aim of the study was to prove whether or not an association exists between the heat shock protein 70 (hsp70) and drug resistance. Tumor samples of 90 patients with previously untreated non-small lung carcinomas were investigated immunohistochemically for expression of resistance related proteins. Additionally, resistance to doxorubicin was determined using a short term test. No association between resistance related proteins. Additionally, resistance to doxorubicin was determined using a short term test. No association between resistance to doxorubicin and hsp70 was found. Of 63 resistant tumors, 33 showed low and 30 high hsp70 expression. Of the 26 sensitive tumors, 11 had low and 16 had high hsp70 expression. No relationship could be found between P-glycoprotein which is related to multidrug resistance and hsp70 expression or between hsp70 expression and expression of topoisomerase II, thymidylate synthase and metallothionein. On the other hand, a trend was noted for tumors with high glutathione S-transferase-pi expression to show high hsp70 expression. In addition, there was a significant relationship between hsp70 and catalase positivity. These data indicate that heat shock and stress promote intracellular oxidative damage and catalase is necessary for protection.

Expression of heat shock proteins, glutathione peroxidase and catalase in childhood acute lymphoblastic leukemia and nephroblastoma

In this study we analyzed the mRNA expression of the heat shock proteins 27 and 70, and the expression of the radical scavenging enzymes catalase and glutathione peroxidase (GPX) in childhood acute lymphoblastic leukemia (ALL, n = 54) and in nephroblastoma (n = 34). We found a significant positive correlation between both heat shock proteins and also between glutathione peroxidase and both heat shock proteins in ALL and nephroblastoma. There was also a significant correlation between catalase and glutathione peroxidase detectable. Furthermore, we investigated whether the expression of the heat shock proteins and the antioxidant enzymes glutathione peroxidase and catalase have implications in the clinical outcome in ALL. However, we found no significant correlation between the expression of these proteins and relapse rate, the relapse free intervals or the overall survival.

Messenger RNA expression of resistance factors and their correlation to the proliferative activity in childhood acute lymphoblastic leukemia

In this report we analyzed the mRNA expression of the resistance-related enzymes DNA topoisomerase II (Topo II), thymidylate synthase (TS), glutathione S-transferase-pi (GST-pi) and glutathione peroxidase (GP) in childhood acute lymphoblastic leukemia (ALL) and their correlation to the proliferative activity, determined by Ki-67. RNA of blast cells from 54 children with untreated ALL were examined by dot blot hybridization. We found a significant positive correlation between Topo II and TS and cell proliferation. No significant correlation was detected between the mRNA expression of the glutathione-dependent enzymes GST-pi or GP and Ki-67. The results were substantiated by a semiquantitative RT-PCR-assay and by immunocytochemistry.

Determination of DNA topoisomerase II in newly diagnosed childhood acute lymphoblastic leukemia by immunocytochemistry and RT-PCR.

The expression of DNA-topoisomerase II was analysed at the protein level in newly diagnosed cases of acute lymphoblastic leukemia (ALL) in children. Blast cells obtained from 81 children with untreated ALL were determined by means of immunocytochemistry. Of the ALL, 49 (60%) were positive for topoisomerase II and 32 (40%) negative. No significant correlation was found between the expression of topoisomerase II and the relapse rate or relapse-free intervals. These results were substantiated by determining the topoisomerase II mRNA expression in a collective of 21 patients by semiquantitative PCR. The PCR-assay and immunocytochemistry corresponded in 13 of 21 cases (62%).