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  • 1
    Electronic Resource
    Electronic Resource
    c-mos immunoreactivity is an indicator of good prognosis in lung cancer (2000)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Histopathology 37 (2000), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Reports concerning the expression of cytoplasmic components of the mitogen-activating protein kinase (MAPK) pathway in lung cancer are limited. One of the molecules participating in this pathway is the product of the c-mos proto-oncogene. In vitro investigations, in somatic cells, have shown that c-mos expression has opposing effects on cell cycle progression suggesting that it may represent an important determinant of aberrant cell function. In this study we analysed, by immunohistochemical means, its status in a series of lung carcinomas and correlated the findings with clinicopathological parameters and survival of the patients.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsSixty cases of lung carcinomas were included in the study. These comprised 52 non-small (NSCLCs) and eight small cell lung carcinomas (SCLCs). Sections from the carcinomas were immunostained with the polyclonal anti-c-mos antibody P-19. Specificity was tested by using the appropriate control peptide and control cell lines. Expression was observed in 63% of the cases, with NSCLCs showing higher reactivity (67%) than SCLCs (37.5%). Staining was observed mainly to the cytoplasm and membranes of the cancerous cells, but some nuclei reacted as well. An intratumour heterogeneous immunoreactivity was noticed. The most interesting and unexpected finding was that c-mos positive staining was associated with better recurrence-free survival in our series, regardless of histological type (P = 0.035). Furthermore, favourable disease-related and recurrence-free survival was observed in the SqC group with c-mos immunoreactivity (P 〈 0.001).〈section xml:id="abs1-3"〉〈title type="main"〉Conclusions c-mos proto-oncogene is expressed in a significant proportion of lung carcinomas and may play a role in its development. The fact that its expression is associated with a relatively good prognosis may be indicative of a negative impact on tumour growth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2559.2000.00898.x
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  • 2
    Electronic Resource
    Electronic Resource
    Expression of p53 protein in laryngeal squamous cell carcinoma and dysplasia: possible correlation with human papillomavirus infection and clinicopathological findings (1994)
    Springer
    Virchows Archiv 425 (1994), S. 481-489 
    Details
    ISSN: 1432-2307
    Keywords: p53 ; Human papillomavirus ; Polymerase chain reaction ; In situ hybridization ; Laryngeal squamous cell carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to evaluate the expression of p53 protein in 28 premalignant and 40 malignant squamous cell proliferations of the larynx and its relationship to tobacco consumption, human papillomavirus infection and differentiation grade of the lesions, p53 expression was examined by means of a microwave post-fixation immunohistochemical method using the PAb 240 and PAb 1801 monoclonal antibodies. HPV infection was assessed by non-isotopic in situ hybridization (NISH) and polymerase chain reaction (PCR). A large proportion of carcinomas (77.5%) and dysplasias (61%) expressed p53. No difference was found between differentiation grades of the lesions regarding p53 detection (P〉0.1), but moderate or intense p53 expression was more frequent in the carcinomas (P〈0.05). A statistical correlation was found between cigarette consumption and both p53 detection and p53 staining intensity (P〈0.05 in each case). HPV study revealed HPV 16 and 18 infection only in carcinomas. The frequency was 28% and the physical state of the virus as demonstrated by NISH was integration into the genome. We observed an inverse relationship between HPV infection and p53 expression (P=0.006). Our findings suggest that p53 overexpression is a common and early event which increases in frequency with progression of laryngeal squamous cell carcinoma. The expression of p53 is influenced by tobacco and high-risk types of HPV.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00197551
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  • 3
    Electronic Resource
    Electronic Resource
    Epidermal growth factor receptor expression in squamous cell lung carcinomas: An immunohistochemical and gene analysis in formalin-fixed, paraffin-embedded material (1993)
    Springer
    Virchows Archiv 423 (1993), S. 295-302 
    Details
    ISSN: 1432-2307
    Keywords: Epidermal growth factor receptor ; Squamous cell lung carcinoma ; Southern blot ; Differential polymerase chain reaction ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epidermal growth factor (EGF) and its receptor (EGFr) constitute an important and well-characterized mitogenic system in various ectodermal tissues. We evaluated the expression of EGFr and examined possible EGFr gene alterations in 18 formalin-fixed, paraffin-embedded squamous cell lung carcinomas (SCLC) by an immunohistochemical assay, Southern blotting and differential polymerase chain reaction (DPCR). The immunohistochemical study employing the F4 and EGF-R1 monoclonal antibodies, directed against the intra- and extra-cellular portion of the receptor respectively, showed EGFr over-expression in 89% of the SCLC cases examined. All cases showed positive immunostaining for both antibodies, thus excluding the possibility of truncated receptors. In addition, analysis of the EGFr gene was carried out by Southern blotting and DPCR on paraffin extracted DNA from the same carcinoma cases. We found amplification of the EGFr gene in 5/18 (27%) SCLCs. All 5 positive cases showed EGFr over-expression, suggesting a possible correlation between the presence of EGFr gene amplification and over-expression of receptor protein. No correlation was observed among EGFr staining, EGFr gene amplification and differentiation of carcinomas. In addition, Southern blot analysis with HER-A2, a probe which hybridizes a sequence of the receptor's intracellular domain, revealed three novelEcoRI restriction fragment patterns. We suggest that these patterns correspond toEcoRI polymorphic sites of the receptor's tyrosine kinase domain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01606894
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  • 4
    Electronic Resource
    Electronic Resource
    Molecular aspects of multiple myeloma (2000)
    Springer
    Annals of oncology 11 (2000), S. 1217-1228 
    Details
    ISSN: 1569-8041
    Keywords: cell cycle ; cytogenetics ; human herpesvirus 8 ; interleukin-6 ; multiple myeloma ; therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Multiple myeloma (MM) is a B-cell neoplasm characterized by bone marrowinfiltration with malignant plasma cells, which synthesize and secretemonoclonal immunoglobulin (Ig) fragments. Despite the considerable progressin the understanding of MM biology, the molecular basis of the disease remainselusive. The initial transformation is thought to occur in a post-germinalcenter B-lineage cell, carrying a somatically hypermutated Ig heavy chain(IGH) gene. This plasmablastic precursor cell colonizes the bone marrow,propagates clonally and differentiates into a slowly proliferating myelomacell population, all under the influence of specific cell adhesion moleculesand cytokines. Production of interleukin-6 by stromal cells, osteoblasts and,in some cases, neoplastic cells is an essential element of myeloma cellgrowth, with the cytokine stimulus being delivered intracellularly via theJack-STAT and ras signaling pathways. While karyotypic changes havebeen identified in up to 50% of MM patients, recent molecularcytogenetic techniques have revealed chromosomal abnormalities in the vastmajority of examined cases. Translocations mostly involve illegal switchrearrangements of the IGH locus with various partner genes (CCND1, FGFR3,c-maf). Such events have been assigned a critical role in MMdevelopment. Mutations in coding and regulatory regions, as well as aberrantexpression patterns of several oncogenes (c-myc, ras) andtumor suppressor genes (p16, p15) have been reported. Keyregulators of programmed cell death (BCL-2, Fas), tumor expansion(metalloproteinases) and drug responsiveness (topoisomerase II alpha) havealso been implicated in the pathogenesis of this hematologic malignancy. Atumorigenic role for human herpesvirus 8 (HHV8) was postulated recently,following the detection of viral sequences in bone marrow dendritic cells ofMM patients. However, since several research groups were unable to confirmthis observation, the role of HHV8 remains unclear. Translation of theadvances in MM molecular biology into novel therapeutic strategies isessential in order to improve disease prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008331714186
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  • 5
    Electronic Resource
    Electronic Resource
    Molecular analysis of p53 gene in laryngeal premalignant and malignant lesions. p53 protein immunohistochemical expression is positively related to proliferating cell nuclear antigen labelling index (1995)
    Springer
    Virchows Archiv 426 (1995), S. 339-344 
    Details
    ISSN: 1432-2307
    Keywords: p53 mutations ; Polymerase chain reaction ; Single strand conformation polymorphism ; Proliferating cell nuclear antigen ; Laryngeal squamous cell carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was undertaken in order to investigate the molecular nature of the p53 gene in 19 laryngeal squamous cell carcinomas and dysplasias. Moreover, we have examined the possible relationship between proliferating cell nuclear antigen (PCNA) expression and p53 protein detection status in 42 laryngeal premalignant and malignant lesions in which 14 of the 19 samples used in the molecular study were included. p53 gene analysis was performed with the single-strand conformation polymorphism technique. PCNA was stained with the peroxidase/antiperoxidase immunohistochemical method using the monoclonal antibody PC-10. Data from previous work concerning p53 expression was used. We found that 9 of 12 of the immunohistochemically p53 positive (+) cases had mutations in exons 5 or 6. In the remaining immunohistochemically p53(+) and p53 negative (−) specimens there was no indication of sequence alterations. Furthermore, we did not observe any deletions in the chromosomal region 17p31.1 which encodes exons 4–8 of the p53 gene. The PCNA labelling index (LI) increased progressively with p53 protein detection status (percentage of cells immunohistochemically positive for p53). The difference between the group with the higher percentage of p53(+) cells and the others was statistically significant. These data show that although there is a discrepancy between immunohistochemical demonstration of p53 and molecular analysis, a large proportion of the former harbours the mutant form of the protein. In addition, p53 overexpression is positively correlated with PCNA LI, a finding which accompanies tumour progression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00191341
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