Neural Cell Adhesion Molecules (NCAM) and NCAM-PSA Expression in Neuroendocrine Lung Tumors

Lantuéjoul, Sylvie; Moro, D.; Michalides, Rob; Brambilla, Christian; Brambilla, Élisabeth

doi:10.1097/00000478-199810000-00012

Cited by 181 publications

(105 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…48,49 It is reported that CD56 is useful for the immunohistochemical differentiation of small cell carcinoma and large cell neuroendocrine carcinoma from nonneuroendocrine carcionomas. [49][50][51] The frequencies of the expressions of CD56 were higher in small cell carcinoma (96%) than in large cell neuroendocrine carcinoma (53%), and the difference was statistically significant in our study.…”

Section: Discussionsupporting

confidence: 48%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

View full text Add to dashboard Cite

The distinction between pulmonary large cell neuroendocrine carcinoma and small cell carcinoma is difficult in some cases. Some propose that these carcinomas should be classified as one high-grade neuroendocrine carcinoma. We examined biological features of small cell carcinoma (n ¼ 23), large cell neuroendocrine carcinoma (n ¼ 17), and classic large cell carcinoma (n ¼ 12). The average ratio of nuclear diameter of the tumor cells to that of lymphocytes for small cell carcinoma was smaller than that for large cell neuroendocrine carcinoma (Po0.0001). The frequencies of the expressions of CD56, mASH1, TTF-1, and p16 were higher and that of NeuroD was lower in small cell carcinoma than in large cell neuroendocrine carcinoma. The frequency of loss of heterozygosity at 3p was higher in high-grade neuroendocrine carcinomas than in classic large cell carcinoma (P ¼ 0.0002). Allelic losses at D5S422 (5q33) were more frequent in small cell carcinoma than in large cell neuroendocrine carcinoma (P ¼ 0.0091). Mean fractional regional loss indices of the tumors were 0.38, 0.65, and 0.72 for patients with classic large cell carcinoma, large cell neuroendocrine carcinoma, and small cell carcinoma, respectively (P ¼ 0.0003). Five-year overall survivals of patients with classic large cell carcinoma, large cell neuroendocrine carcinoma and small cell carcinoma in stage I were 67, 73, 60%, respectively. Patients with NeuroD expression had better survivals, and those with p63 expression had poorer survivals in large cell neuroendocrine carcinoma. Patients with TTF-1 expression had poorer survivals in small cell carcinoma. Our data suggest that large cell neuroendocrine carcinoma and small cell carcinoma are different morphologically, phenotypically, and genetically, although there are some overlapping features. Although further studies are needed to analyze the biological behavior of high-grade neuroendocrine carcinomas including sensitivity to chemotherapy, the pathological distinction of large cell neuroendocrine carcinoma from small cell carcinoma may be necessary to treat the patients with neuroendocrine tumors.

show abstract

Section: Discussionsupporting

confidence: 48%

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

et al. 2006

View full text Add to dashboard Cite

show abstract

“…PolySia-specific retargeting also resulted in effective adenoviral infection of polySia-expressing human tumors in vitro and in vivo (e.g., SCLC, neuroblastoma, and rhabdomyosarcoma). PolySia is also an attractive molecular target because it is associated with malignant features (20)(21)(22). Furthermore, the high degree of tumor selectivity promises a lower risk for offtarget infection.…”

Section: Discussionmentioning

confidence: 99%

“…PolySia-expression is high during embryonic development (17,18) but absent from peripheral organs in adult humans (19). Remarkably, polySia is frequently expressed in tumors of neuroendocrine origin such as SCLC, glioblastoma, medulloblastoma, and rhabdomyosarcoma (20). A prominent function of polySia is the regulation of cell-cell contacts because the presence of this negatively charged molecule on the cell surface promotes intercellular repulsion.…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, polySia expression has been correlated with metastatic potential and epithelial-to-mesenchymal transition (21,22). The prevalence of polySia on invasively growing tumors is associated with poor clinical prognosis (20), and the absence in healthy peripheral tissues makes it an attractive molecular target for oncolytic adenovirus retargeting.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PolySia-Specific Retargeting of Oncolytic Viruses Triggers Tumor-Specific Immune Responses and Facilitates Therapy of Disseminated Lung Cancer

Kloos

Woller

Gürlevik

et al. 2015

Cancer Immunology Research

View full text Add to dashboard Cite

Polysialic acid (polySia) is expressed on several malignant tumors of neuroendocrine origin, including small cell lung cancer. In this study, we investigated the therapeutic efficacy of tumor-directed T-cell responses, elicited by polySia-retargeted oncolytic adenovirus infection, in an orthotopic murine model of disseminated polySia-positive lung cancer. In several cell lines, we demonstrated highly polySia-selective retargeting of adenoviral infection using a bispecific adapter comprising the ectodomain of the coxsackievirus/adenovirus receptor and a polySia-recognizing single-chain antibody domain. PolySiadependent systemic infection in vivo facilitated effective uptake of viruses in subcutaneous polySia-expressing human tumors, whereas hepatic viral load and hepatotoxicity were significantly reduced. The impact and nature of antitumoral immune responses triggered by systemic delivery of polySia-retargeted oncolytic adenoviruses were investigated in an orthotopic model of disseminated lung cancer. Interestingly, improved transduction by polySia-retargeted oncolytic adenoviruses led to CD45-positive cell infiltrates in close association with large lytic areas. Consistently, enhanced tumor regression and prolonged survival was only observed in immunocompetent mice, but not in T-celldeficient mice. To investigate whether improved systemic infection by polySia retargeting would elicit a tumor-specific T-cell response, we screened the used lung cancer cells for mutated oncogenes by complete exon sequencing. In agreement with our other results, only retargeted oncolysis was able to induce a significant response specific for the tumor-associated neoepitope Gsta2-Y9H. In conclusion, we demonstrated that effective retargeting of oncolytic adenovirus against polySia-expressing tumors elicits an effective tumor-directed T-cell response after systemic virus delivery and facilitates therapy of disseminated lung cancer.

show abstract

“…17,18 Tissue Processing for Image Analysis For measurement of cell nuclei, single-cell preparations were used. From each case, the most representative tissue block, in which the surrounding normal tissue could be clearly separated from the tumor, was selected.…”

Section: Methodsmentioning

confidence: 99%

Quantitative nuclear texture features analysis confirms WHO classification 2004 for lung carcinomas

et al. 2006

View full text Add to dashboard Cite

The purpose of this study was to discriminate the main subsets of lung carcinomas of the WHO classification of 2004 by nuclear chromatin texture feature analysis. Our collective comprised 56 typical and 19 atypical carcinoids, 37 small-cell carcinomas, 15 large-cell neuroendocrine carcinomas, 42 adenocarcinomas, and 26 squamous cell carcinomas. After Feulgen staining, cell nuclei were automatically measured using a highresolution image analyser (CytoSavant Oncometrics, Vancouver, BC, Canada). Texture features describing the granularity and the compactness of the nuclear chromatin were extracted for calculation of classification rules, which allowed the discrimination of different tumor groups. By applying the classification rule that described the granularity of the nuclear chromatin (defined by four different parameters) small-cell and non-small-cell lung carcinoma could correctly be discriminated in 93%. No significant discrimination was possible between the different subtypes of large-cell carcinomas, including large-cell neuroendocrine carcinoma. When using compactness of chromatin (defined by four texture parameters) as a means of discrimination, carcinoids and non-small-cell lung carcinomas were correctly distinguished in 92%. No significant discrimination between neuroendocrine tumors was achieved though. Our findings are in accordance with the new WHO classification of 2004: neuroendocrine tumors of the lung are now classified according only to their mitotic counts and presence of necrosis but not by their morphology; their discrimination by the means of nuclear image analysis is not sufficient and therefore not appropriate any longer.

show abstract

Neural Cell Adhesion Molecules (NCAM) and NCAM-PSA Expression in Neuroendocrine Lung Tumors

Cited by 181 publications

References 26 publications

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

PolySia-Specific Retargeting of Oncolytic Viruses Triggers Tumor-Specific Immune Responses and Facilitates Therapy of Disseminated Lung Cancer

Quantitative nuclear texture features analysis confirms WHO classification 2004 for lung carcinomas

Contact Info

Product

Resources

About