We have found markedly deficient expression of the class I major histocompatibility antigens HLA-A,B,C and beta 2m on human small-cell lung cancer (SCLC) lines and fresh tumor samples. The deficit of ...HLA-A,B,C and beta 2-microglobulin (beta 2m) antigen expression was demonstrated with both radiobinding assays and indirect immunofluorescence assays. Immunoprecipitation of metabolically labeled cells with antibodies to class I antigens showed most SCLC lines to have synthesized almost no beta 2m and HLA-A,B,C proteins. Northern blot analysis, using human HLA-A,B, and beta 2m cDNA probes, showed that almost all SCLC lines tested had markedly decreased amounts of HLA and beta 2m mRNA, but both gene products could be induced with interferon treatment of SCLC lines. We conclude that human SCLC, in contrast to other lung cancer types, is characterized by greatly reduced transcription of HLA-A,B,C and beta 2m genes, which suggests the existence of a mechanism for evading the host immune response to the tumor and of an E1a-like product in this type of tumor cell.
Formalin-fixed paraffin-embedded tissue specimens obtained by fine needle aspiration of pancreatic masses from 47 patients were examined retrospectively for cytology and the presence of mutant ...c-K-ras oncogenes. Point mutations of c-K-ras in codon 12 were detected by RNA-DNA RNAse A mismatch cleavage after in vitro DNA amplification of the cellular c-K-ras sequences by the polymerase chain reaction. Of the 36 patients with pancreatic adenocarcinoma, mutant c-K-ras oncogenes were detected in 18 of 25 (72%) with malignant cytologies, 2 of 8 (25%) with atypical cytologies, and 0 of 3 with benign aspiration cytologies. The remaining 11 patients without pancreatic adenocarcinomas did not have mutant c-K-ras genes detectable by the assay. The diagnosis of pancreatic adenocarcinoma was based upon clinical follow-up. The presence of mutant c-K-ras oncogenes did not significantly affect survival in the patients studied. Mutant c-K-ras genes were found at the time of initial clinical presentation in the majority of pancreatic adenocarcinomas, suggesting an important role of the mutation in oncogenesis. In conjunction with cytology, our approach represents an application for cancer diagnosis at the molecular genetic level.
Previous studies of fine-needle aspiration (FNA) specimens from lymph nodes of patients with tuberculosis (TB) and infection with the human immunodeficiency virus (HIV) have often involved small ...numbers of specimens and have produced conflicting results. We reviewed 93 FNA specimens from peripheral lymph nodes in a consecutive series of 79 patients with TB to compare results for patients with and without HIV infection. The 45 patients with HIV infection in the series were more frequently male, more likely to have negative results on a purified protein derivative tuberculin skin test, and they had more disseminated disease. Granulomatous inflammation, a positive result on a culture, acid-fast bacilli, or necrosis was found in 71% of the studies. Identification of granulomatous inflammation occurred at a similar rate in FNA specimens from patients with HIV infection (16%) and without HIV infection (21%; P = .56). Necrosis was the sole reported finding in a significant subset of cases (16%), occurring in patients with and patients without HIV infection. FNA of peripheral lymph nodes of patients with TB was an effective diagnostic test. Granulomatous inflammation and other FNA findings in peripheral lymph nodes of patients with TB were similar in those with and those without HIV infection.
Immunohistochemical analysis of 30 paraffin-embedded astrocytic neoplasms was performed to correlate the expression of intermediate filament proteins with histologic subtype. Each tumor was studied ...with monoclonal antibodies to keratin, vimentin, desmin, 200-kd neurofilament protein, and glial fibrillary acidic protein (GFAP). Immunoreactivity with the anti-keratin monoclonal antibodies AE1 and AE3 was demonstrated in 24 cases (80%) including 4 of 6 (66%) well-differentiated astrocytomas (WDAs), 10 of 12 (83%) anaplastic astrocytomas (ANAs), and 10 of 12 (83%) glioblastomas multiforme (GBMs). These cases were further studied with the monoclonal antikeratin antibodies 34 beta E12 and 34 beta H11. Of the 24 AE1/AE3-positive cases, 14 (58%) reacted with 34 beta E12. None of the cases was reactive with 34 beta H11. Vimentin expression was demonstrated in 24 cases (80%), including 2 of 6 (33%) WDAs, 11 of 12 (92%) ANAs, and 11 of 12 (92%) GBMs. Coexpression of keratin and vimentin was observed in 20 cases (67%), including 2 of 6 WDAs, 9 of 12 (75%) ANAs, and 9 of 12 (75%) GBMs. Immunoreactivity with GFAP antibody was present in all 30 (100%) cases, but none of the tumors was reactive with antibodies to desmin or 200-kd neurofilament protein. These findings demonstrate that expression of both keratin and vimentin intermediate filaments is common in astrocytic neoplasms regardless of histologic grade.
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