Summary A prospective study was performed in patients with non-small cell lung cancer (NSCLC) to evaluate the prognostic importance of multiple molecular marker (p53, c-Ki-ras, c-erbB-2) testing. 103 patients with potentially curative resections (RO resection) for NSCLC in histopathological stages I-IIIA were included. SSCP analysis and DNA sequencing for p53 and c-Ki-ras genes were performed on paired tumour and normal lung tissue samples and immunohistochemistry (c-erbB-2) was done on frozen tissue sections with a specific anti-c-erbB-2 monoclonal antibody. 46/103 (44.6%) NSCLC showed p53 mutations and 17/103 (16.5%) c-Ki-ras mutations including 12/37 (32.4%) adenocarcinomas. Overexpression of c-erbB-2 (p185) was detected in 56/103 (54.4%) tumours. 24/103 (23.3%) NSCLC were negative for alterations in all 3 parameters (c-Ki-ras, p53 and p185) whereas 79/103 (76.7%) were positive for at least one of the 3 parameters. In a regression model including a multiple molecular marker parameter (negative for all 3 markers versus positive for at least one marker), histopathological stage (P < 0.00001), respectively the pT (P < 0.01) and pN (P < 0.00001) categories and the multiple molecular marker parameter (P < 0.01) were of significant prognostic importance. This study demonstrates that testing 3 molecular markers (c-Ki-ras, p53 and c-erbB-2) improves estimation of prognosis compared to single marker testing and appears to define low (82.6% ± 7.9% 5-year survival) and high risk (40.2% ± 5.5% 5-year survival) groups for treatment failure in potentially curative (RO) resected NSCLC.

In B-cells, activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. AID introduces mutations in immunoglobulin variable regions (IGV) during B-cell receptor affinity maturation, but may also introduce aberrant mutations into non-immunoglobulin genes, most commonly BCL6. Follicular lymphoma (FL) B-cells constitutively express AID and undergo CSR, SHM and aberrant SHM. We have studied AID expression, the presence of SHM mutations, CSR, and aberrant SHM in BCL6 in a cohort of 75 FL patients. Whereas IgM-expressing (non-switched) FL were characterized by an expected positive correlation between AID and IGV and BCL6 mutations, isotype-switched FL showed dissociation between AID expression and aberrant SHM, and inverse correlation between SHM and AID expression. Our results unveil two manifest biological subgroups of FL and indicate that the specific dissociation between AID and SHM after isotype switch may correlate with the clinical outcome of this heterogeneous disease.

In burn victims with short survival times of ≤1 h after fire exposure, the immunohistochemical expression profiles of TNF-α, IL-8 and ICAM-1 in the lungs were not altered enough to prove an instant inflammatory reaction in these cases. Nevertheless, the positive reaction of TNF-α in erythrocytes of burn victims may indicate the beginning of a non-specific immune response to fire-induced inhalation trauma.

This study clearly shows that BM osteoclasts stay TRAP-positive for 7 days post-mortem, although with markedly reduced TRAP-SIs compared with biopsies. Since TRAP-SIs were not correlated with the duration of PMI, TRAP staining of BM osteoclasts cannot serve as a tool to determine the time of death of a patient.