The precise immune mechanisms of neuronal death in anti-Hu-associated paraneoplastic encephalomyelitis (PEM) are unclear. We performed an immunohistochemical study on postmortem brain tissue from 11 patients with anti-Hu-associated PEM to further characterize the immune reaction and to ascertain possible mechanisms of neuronal death. To analyze inflammatory infiltrates, antibodies against lymphocyte subpopulations (CD3, CD20, CD4, CD8), macrophage and activated microglia (CD68), major histocompatibility complex (MHC) classes I and II (HLA-ABC and HLA-DR), and the intercellular adhesion molecules (ICAM) -1 and -3 were used. Cell death mechanisms were defined using antibodies against the cytotoxic protein TIA-1, the C9neo component of complement, the Fas receptor (CD95) and its ligand, the apoptosis effector activated caspase-3, and the apoptosis inhibitor Bcl-2. A great number of T cells expressing the cytotoxic protein TIA-1 was observed, mainly in clusters around neurons. ICAM-1 immunoreactivity was increased in the neuropil and reactive astrocytes in areas of inflammation within the central nervous system and in satellite cells of pathological dorsal root ganglia surrounding apparently normal sensory neurons. By contrast, Fas, FasL, C9neo, and activated caspase-3 immunoreactivities were negative in pathological areas. Bcl-2 immunoreactivity was found in satellite cells, but not in sensory neurons of normal and pathological dorsal root ganglia. Our data point out to an induction of a cytotoxic, non-apoptotic, neuronal death in anti-Hu-associated PEM. The increased ICAM-1 immunoreactivity may favor the infiltration of lymphocytes in the pathological areas.

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The findings suggest that detection of free circulating DNA in sera of NSCLC patients is incidentally linked to the systemic nature of lung cancer even at the earliest stage. These observations provide the first hint that serum tumor DNA is present in NSCLC patients. The detection of DNA from cancer cells in the sera of NSCLC patients could be useful for monitoring relapse in a relatively non-invasive way, and the potential sensitivity of this test may help in selecting candidates for adjuvant chemotherapy.

The detection of 14‐3‐3 protein in cerebrospinal fluid by immunoblotting is useful for the diagnosis of Creutzfeldt‐Jakob disease (CJD). We found 14‐3‐3 protein in 10 of 80 (12.5%) patients with paraneoplastic neurological disorders (PNDs), whose presenting symptoms may mimic those of CJD. In 47 of 48 CJD patients, the 14‐3‐3 protein was detected as a single band, and it was detected as a double band in 1 patient. The double‐band pattern was observed in 9 of the 10 14‐3‐3 protein–positive patients with PNDs. The 14‐3‐3 protein assay may be positive in PND patients, but the immunoblotting pattern distinguishes most PND samples from those of CJD.

To better understand whether replication-error-type instability (RER 1 ) is a frequent genetic alteration event in surgicalpathologic stage-I non-small-cell lung cancer (NSCLC) and identify whether it constitutes an independent prognostic parameter, we examined 35 surgical-pathologic stage-I-NSCLC patients with complete follow-up in all cases for at least 49 months. The tumor samples and the paired histopathologically normal lung samples for each patient were analyzed for 8 microsatellite markers located at chromosomes 3p and 2p to investigate microsatellite alterations such as RER 1 and loss of heterozygosity (LOH). Single-strandconformation-polymorphism analysis for detection of p53 and k-ras gene mutations was also carried out. Genetic data were correlated with clinical outcome and histopathologically established prognostic factors. RER 1 at one or both chromosomes was identified in 24 of the 35 patients; 9 patients showed LOH. A statistically significant correlation was found between RER 1 and poor prognosis (p 5 0.001). Furthermore, RER 1 proved to be an independent factor that predicted decreased survival, ranking first, followed by visceral pleural invasion. A trend towards worse survival was strongest in the group of patients with tumor size greater than 3 cm (T2). Patients with other genetic abnormalities, such as K-ras mutations, p53 mutations or LOH, had prognoses similar to those of patients without such aberrations. The data suggest that RER 1 is common in NSCLC, that it may provide important prognostic information in stage-I NSCLC and serve as a useful marker for relapse-risk assessment in operable NSCLC patients. Int.