CRMP5 antibodies found in a patient with limbic encephalitis and myasthenia gravis.

Collapsin response mediator protein 5 (CRMP5) antibodies are often associated with thymoma or small cell lung cancer and paraneoplastic syndromes such as limbic encephalitis (LE). A patient is described with myasthenia gravis who, following thymectomy and immunosuppression, acquired a viral infection and developed LE and increased levels of serum CRMP5 antibodies. The cognitive symptoms improved and CRMP5 antibody levels decreased after plasma exchange, suggesting that CRMP5 antibodies may have contributed to the development of LE.

An immunoprecipitation assay for the detection of onconeural antibodies.

INTRODUCTION: Onconeural antibodies are found in some patients with cancer, and are associated with paraneoplastic neurological syndromes. METHOD: A multi-well adapted fluid-phase immunoassay using radiolabelled recombinant onconeural proteins for the detection of onconeural antibodies is described. RESULT AND CONCLUSION: This immunoprecipitation technique is more sensitive in detecting onconeural antibodies than immunohistochemistry and immune blots.

Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique.

Onconeural antibodies are found in patients with cancer and are associated with paraneoplastic neurological syndromes (PNS). The objective of the present study was to assess the frequency of Yo antibodies in ovarian and breast cancer using a sensitive immunoprecipitation technique, and to look for any association of Yo antibodies with neurological symptoms and prognostic factors. A multiwell adapted fluid-phase immunoassay using radiolabelled recombinant cerebellar degeneration related protein (cdr2), produced by coupled in vitro transcription/translation was used for the detection of Yo antibodies. This technique combines high specificity and sensitivity with high sample analysing capacity for the antibody in question. Sera or EDTA-blood from 810 ovarian (n = 557) and breast cancer (n = 253) patients were analysed for Yo antibodies by immunoprecipitation, as well as immunofluorescence and immune blots. Two hundred healthy blood donors and sera from 17 patients with paraneoplastic cerebellar degeneration and Yo antibodies served as controls. Immunoprecipitation was more sensitive in detecting Yo antibodies than immunofluorescence and immune blots. The prevalence of Yo antibodies was 13/557 (2.3%) in ovarian cancer and 4/253 (1.6%) in breast cancer using immunoprecipitation. Yo antibodies were not correlated with specific histological subgroups. The Yo index of ovarian cancer patients in FIGO stage IV was higher compared to FIGO stage I-III. The prevalence of Yo antibodies was 3 times higher in patients with stage III breast cancer than in stage I and II. Only 2/17 (11.8%) patients with Yo antibodies detected during the screen of 810 cancer patients had PNS. The results show that the prevalence of Yo antibodies is low in ovarian and breast cancer. Yo antibodies may be associated with advanced cancer, but less often with PNS.

Hu and voltage-gated calcium channel (VGCC) antibodies related to the prognosis of small-cell lung cancer.

PURPOSE: Hu antibodies previously have been associated with longer survival of patients with small-cell lung cancer (SCLC). Voltage-gated calcium channel (VGCC) antibodies play a pathogenic role in Lambert Eaton myasthenic syndrome, which is also associated with SCLC. These antibodies may reduce tumor growth in patients with the neurologic disease, but it is not clear whether they provide prognostic information in those without neurologic symptoms. PATIENTS AND METHODS: Two hundred patients with SCLC (age 39 to 79 years; mean, 62.3 years; 129 males and 71 females) receiving chemotherapy were studied for the presence of Hu and VGCC antibodies. Sera were examined for Hu antibodies by an in vitro transcription-translation-based immunoprecipitation technique and by immunohistochemistry/dot blot. VGCC (P/Q subtype) antibodies were detected by radioimmunoassay. Survival analysis was used to analyze the data. Results Hu antibodies were detected in 51 of 200 patients (25.5%) by in vitro transcription-translation-based immunoprecipitation and in 37 of 200 patients (18.5%) by immunohistochemistry or dot blot, whereas VGCC antibodies were detected in only 10 of 200 patients (5%). The presence of Hu antibodies did not correlate with VGCC antibodies, and there was no association between Hu or VGCC antibodies and the extent of disease or survival. CONCLUSION: Hu and VGCC antibodies are found in a proportion of SCLC patients, irrespective of neurologic symptoms, but their presence does not correlate with the prognosis of the SCLC.

Paraneoplastic antibodies against HuD detected by a sensitive radiobinding assay.

Patients with paraneoplastic encephalomyelitis(subacute sensory neuronopathy) (PEM/SSN), most commonly associated with small-cell lung cancer (SCLC), frequently harbor Hu antibodies, which are usually detected by indirect immunohistochemistry or immunoblot. We developed a new radioimmunobinding assay to detect Hu antibodies based on in vitro transcribed and translated (ITT) HuD. High levels of Hu antibodies were detected in all seven PEM/SSN patients tested, but not in any of 15 patients with other paraneoplastic syndromes, 20 patients with Sjögren's syndrome, 20 patients with miscellaneous tumors and 99 of 100 blood donors. One of the blood donors had low levels of Hu antibodies. The radiobinding assay detected Hu antibodies in 45 of 191 (24%) patients with SCLC, in comparison with immunofluorescence and immuno dot blot, where only 34 of 191 (18%) were detected. All patients with Hu antibodies detected by immunofluorescence and immuno dot-blot were also positive by the radioimmunobinding assay. The results demonstrate that this assay is very specific and sensitive for the detection of Hu antibodies.

Frequent mutations of the p53 gene in cutaneous melanoma of the nodular type.

The frequency and significance of p53 alterations in cutaneous melanoma have not been completely clarified. In the present study, 31 primary melanomas of the nodular type and 15 metastases occurring between 1981 and 1983 were studied with respect to mutations in exons 7 and 8, as well as to p53 protein immunostaining using different antibodies. Altogether 13% of the primary tumors showed strong p53 staining using the DO-7 antibody. Different results were obtained with other antibodies. Seven mutations were found in primary and metastatic tumors; all of these were single base changes, most of which occurred in the core domain of the p53 protein responsible for sequence-specific DNA binding (residues 102-293). The mutations were not significantly associated with p53 staining results, and p53 alterations (mutations or marked immunopositivity) had no prognostic value. Our results indicate that point mutations in exons 7 and 8 are more frequent than previously reported in primary melanomas, and such changes may be important for the development of certain melanoma subgroups.