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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine-specific protein (NSP)-reticulons are endoplasmic reticulum-associated protein complexes, which have been identified as markers for neuroendocrine differentiation. In this study, the expression of two members of the family of NSP-reticulons, NSP-A and NSP-C, have been investigated in different types of lung cancer and compared with the expression patterns of five conventional neuroendocrine markers, the neural cell adhesion molecule (NCAM), synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. NSP-A and NSP-C antibodies were reactive with most carcinoid tumour and small cell lung carcinoma (SCLC) cases, while atypical carcinoid tumours showed a variable expression. In the total group of neuroendocrine tumours, a high concordance of expression was found between NSP-A and NSP-C, while their expression correlated well with NCAM and synaptophysin positivity. Chromogranin A, Leu-7, and neurofilament proteins were shown to be expressed to a limited extent in these neuroendocrine tumours. In a selected group of non-SCLCs known to exhibit neuroendocrine features, NSP-A expression was detected at much higher frequency than NSP-C. In virtually all NSP-A positive cases, this expression was associated with one or more of the other neuroendocrine markers. NSP-A expression showed a stronger correlation with conventional neuroendocrine markers than NCAM. In detecting neuroendocrine differentiation in non-SCLC, NSP-A is more sensitive than synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. It is concluded that NSP-reticulons are valuable markers in the diagnosis of neuroendocrine differentiation in non-SCLC and should be used in conjunction with NCAM.
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PMID:A comparison of NSP-reticulons with conventional neuroendocrine markers in immunophenotyping of lung cancers. 922 37

To determine the neuroendocrine (NE) features of thymic epithelial tumor, immunohistochemistry and electron microscopy studies were performed on eight NE tumors (thymic carcinoids) and 26 non-NE tumors (nine thymic carcinomas, five atypical thymomas, and 12 thymomas other than lymphocytic thymoma). Immunohistochemical studies were performed with antibodies against general markers for NE cells (synaptophysin, alpha subunit of a guanine nucleotide-binding protein, Go, and small-cell lung carcinoma cluster 1 antigen), and a broad panel of antibodies for hormonal substances. Thymic carcinoid showed synchronous diffuse immunoreactivity for the three NE markers and contained cells that were positive for a variety of hormonal products: human chorionic gonadotropin (hCG) alpha-subunit (eight of eight), hCG beta-subunit (three of eight), adrenocorticotropic hormone (ACTH) (three of eight), calcitonin (two of eight), calcitonin gene-related peptide (two of eight), and serotonin (one of eight). Conversely, although positivity for NE markers was neither synchronous nor diffuse in non-NE tumors, seven of nine thymic carcinomas, three of five atypical thymomas (focal or dispersed distribution), and none of the five thymomas were positive for at least two of these NE markers. A small number of neoplastic cells were positive for hCGalpha-subunit or ACTH in three thymic carcinomas and one atypical thymoma. Ultrastructurally, dense core granules (DCG) were much more frequent in thymic carcinoid, but several DCG-like granules were identified in 12 of 13 non-NE tumors with or without immunoexpression of NE markers. The presence of focal or dispersed NE cells in thymic carcinoma and atypical thymoma may reflect multidirectional differentiation within the tumor, which, like cytological atypia, epithelial CD5 expression, and lack of immature T cell infiltration, may be another feature of this group at thymic tumors.
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PMID:Neuroendocrine differentiation in thymic epithelial tumors with special reference to thymic carcinoma and atypical thymoma. 956 81

Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information. Non-small cell lung cancer patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of HER2 (c-erbB-2), a membrane-bound receptor with tyrosine kinase activity, has been associated with shortened survival. The Cancer and Leukemia Group B (CALGB) performed a study of patients with stage IIIA (N2 nodes positive) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery, then post-operative therapy consisting of sequential chemotherapy and radiation therapy. Since all patients underwent mediastinoscopy, this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response. In particular, we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy. We performed immunohistochemical analysis for a panel of NE markers [neuron-specific enolase (NSE), Leu-7, chromogranin A (ChrA), synaptophysin (Syn)], HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers. Secondary endpoints were a correlation with chemotherapy response and survival. Slides were scored for intensity (0-4) and percentage of cells positive (0-4). Of 61 eligible patients, there were 38 with both pre- and post-chemotherapy specimens. When both intensity of staining and percentage of positive cells were considered, post-chemotherapy specimens had a higher percentage of positive NE markers compared with pre-chemotherapy. In addition, there was no correlation between NE marker, HER2 or CEA expression (prior to or post treatment) and response to chemotherapy or survival. These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer.
Lung Cancer 1998 Sep
PMID:Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: a Cancer and Leukemia Group B study. 985 98

We report a case of unique double primary lung cancers with neuroendocrine features in a 63-year-old male smoker. The mass in the left lower lobe (LLL) was a small cell/large cell carcinoma with spindle cell sarcomatous areas and organoid structure. The mass in the left upper lobe (LUL) was a tubular adenocarcinoma with neuroendocrine features including organoid nests showing occasional rosette formation, nuclear palisading in the periphery of the nests and positive immunoreaction for CD56, chromogranin A and synaptophysin. The difference in histological structures between the two masses led us to diagnose double primary lung cancer. The combination of small cell lung carcinoma and spindle cell carcinoma is very uncommon. The relationship between LLL and LUL tumors remains unclear. Multiple lung cancers with neuroendocrine features have only rarely been reported in the literature. The patient in our case died of widespread cancer 2 years and 4 months after the surgery without adjuvant chemotherapy, a longer postoperative survival time than in cases of ordinary extensive small cell lung cancer. Multiple lung cancers with neuroendocrine features are extremely rare and similar cases have not been reported in the literature. Neuroendocrine differentiation has attracted widespread attention and, therefore, examining neuroendocrine features in lung cancers is important.
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PMID:A case of synchronous double primary lung cancer with neuroendocrine features. 1034 47

Several studies have suggested that non-small cell lung cancer (NSCLC) patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of p53 and HER2 may confer relative chemotherapy resistance and shortened survival. The Cancer and Leukemia Group B performed a series of studies involving sequential chemotherapy followed by radiation for patients with unresectable stage III NSCLC. The objectives of this study were to analyze pathological specimens using immunohistochemistry for NE markers, p53 and HER2 to determine if there was a correlation between marker expression and response or survival. Of 160 eligible patients, 28 (18%) were not evaluable because of inadequate material. The percentage of specimens positive for markers was as follows: neuron-specific enolase 38%, Leu-7 2%, chromogranin A 0%, synaptophysin 5%, > or =2+NE markers 3%, p53 61%, and HER2 65%. There was no statistically significant correlation between any individual marker and response to induction chemotherapy or response to combined chemotherapy/radiation except for synaptophysin. Six of 6 (100%) synaptophysin positive tumors responded by the completion of all therapy compared with 69/125 (55%) synaptophysin negative tumors (P=0.04). None of the individual markers had a significant effect on survival in univariate analysis. Neuron-specific enolase was marginally significant in multivariate analysis (P=0.08). In conclusion, this study did not demonstrate that expression of NE markers, p53 and HER2 were predictive of response to chemotherapy, combined chemotherapy/radiation or for survival in this group of patients with stage III NSCLC. Future studies must employ either different markers or be performed on more adequate surgical specimens.
Lung Cancer
PMID:Use of neuroendocrine markers, p53, and HER2 to predict response to chemotherapy in patients with stage III non-small cell lung cancer: a Cancer and Leukemia Group B study. 1155 6

In small-cell lung carcinoma (SCLC) tumour cell contamination of leukaphereses is unknown. The present study was performed to define appropriate markers for reverse transcriptase polymerase chain reaction (RT-PCR), then to assess the contamination rate of leukaphereses and corresponding bone marrow samples. Immunocytochemistry (ICC) and RT-PCR methods were also compared. Among the 33 patients included, analyses were performed in 16 who had multiple leukaphereses and 17 who had only bone marrow. Leukapheresis products and bone marrow were analysed by ICC using several specific monoclonal antibodies against neural-cell adhesion molecule (N-CAM), epithelial glycoprotein (EGP-40) and cytokeratins (CK). Samples were also analyzed by RT-PCR for expression for N-CAM, synaptophysin, neuron-specific enolase, chromogranin, cytokeratin-18/-19, CEA, EGP-40, apomucin type 1 (MUC-1) and human endothelial cell-specific molecule (ESM-1). Using ICC staining, contaminating tumour cells were detected in 34% of leukaphereses (27% in patients with limited disease and 43% in those with extensive disease). N-CAM was the most reliable marker for detection of contamination. For RT-PCR, CK-19 and CEA were the only appropriate markers. Positive signal rate in leukaphereses increased to 78% (89% for patients with limited disease and 67% for extensive disease). In bone marrow, both techniques were in agreement whereas in leukaphereses, RT-PCR was better than ICC. A high rate of tumour cell contamination was demonstrated not only in bone marrow but also in leukaphereses from SCLC patients. The most appropriate technique was RT-PCR mainly in patients with limited disease.
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PMID:High tumour contamination of leukaphereses in patients with small cell carcinoma of the lung: a comparison of immunocytochemistry and RT-PCR. 1174 93

Non-small-cell lung carcinoma (NSCLC) describes a histologically heterogeneous group of tumours with variable clinical behaviour. Performance status, tumour stage and histological type have important prognostic implications, but clinical outcomes in individual patients remain unpredictable. A significant minority of NSCLCs (10%-30%) show neuroendocrine (NE) differentiation, and a number of studies have attempted to evaluate the therapeutic and prognostic significance of the expression of NE markers on the basis of the theoretical assumption that NE-differentiated tumours may be associated with an adverse prognosis and greater chemosensitivity. However, the results of these studies are conflicting: some have found that NE differentiation has a negative impact on survival, but others have failed to demonstrate any correlation with prognosis. Similar discrepancies have also been observed in terms of chemosensitivity. Nevertheless, these data are difficult to interpret because there is no gold standard defining NE differentiation, as is shown by the fact that the proportion of NE-differentiated NSCLCs varies according to the technique and marker used, although chromogranin A and synaptophysin show the best correlation with ultrastructural evidence of NE differentiation. In conclusion, there is no doubt that caution is required when interpreting the results of a number of studies questioning the clinical impact of the NE features of NSCLCs.
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PMID:Clinical significance of neuroendocrine phenotype in non-small-cell lung cancer. 1176 37

The clinical significance of neuroendocrine (NE) differentiation is unclear in large cell carcinoma (LCC) of the lung. Fifty-five surgically resected carcinomas of the lung with an original pathologic diagnosis of LCC were reviewed histologically with special attention to NE morphology. Antibodies against neural cell adhesion molecule (NCAM), chromogranin A (CGA) and synaptophysin (SY) were used to confirm the NE differentiation. Thirteen (24%) cases were classified as large cell neuroendocrine carcinoma, 9 (16%) as LCC with NE differentiation, and 33 (60%) as pure LCC. There was no significant difference in overall survival between the three groups. When the 55 carcinomas were divided into three groups depending on the number of NE marker expression, there was significantly better overall survival in the NE > or = 2 (P = 0.02). Multivariate analysis proved NE > or = 2 was an independent predictor of survival. The number of NE markers was more important in terms of survival than histological sub-classification.
Lung Cancer 2002 Nov
PMID:Immunohistochemical neuroendocrine differentiation is an independent prognostic factor in surgically resected large cell carcinoma of the lung. 1239 30

Histidine decarboxylase is one of the enzymes of the amine precursor uptake and decarboxylation system and is known to be distributed in mast cells and enterochromaffin-like cells. With the hypothesis that histidine decarboxylase expression is a marker for neuroendocrine differentiation, we studied the immunoreactivity of histidine decarboxylase in neuroendocrine cells and tumors of the thyroid gland, adrenal medulla, lung, and gastrointestinal tract. Formalin-fixed paraffin sections were subjected to immunohistochemistry using anti-histidine decarboxylase antibody, and the sensitivity and specificity were compared with those of conventional neuroendocrine markers (CD56, chromogranin A, synaptophysin, and neuron-specific enolase). Enterochromaffin or enterochromaffin-like cells, adrenal chromaffin cells, and thyroid C-cells were positive for histidine decarboxylase, and related tumors (carcinoid tumor, pheochromocytoma, medullary carcinoma) showed a high percentage of positive staining. Furthermore, we used the antibody to distinguish small cell lung carcinoma from non-neuroendocrine lung carcinoma and also to detect neuroendocrine differentiation in large-cell neuroendocrine carcinoma and gastrointestinal small-cell carcinoma. The anti-histidine decarboxylase antibody stained most small cell lung carcinoma (18 of 23, sensitivity 0.78), and was rarely reactive with non-neuroendocrine lung tumors (2 of 44; specificity, 0.95). These values were close to those obtained from CD56 staining (sensitivity/specificity, 0.87/0.98). Histidine decarboxylase was also positive for 6 of 12 large cell neuroendocrine carcinomas and 4 of 7 gastrointestinal small cell carcinomas. In conclusion, we demonstrated that histidine decarboxylase is useful to distinguish between small cell lung carcinoma and non-neuroendocrine carcinoma and to demonstrate neuroendocrine differentiation.
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PMID:Histidine decarboxylase expression as a new sensitive and specific marker for small cell lung carcinoma. 1252 16

Small cell carcinoma arising in the esophagus is a relatively rare disease. In the more common small cell carcinoma of the lung, the diagnostic significance of several new markers has been recently reported. This study used immunohistochemical techniques in addition to clinicopathological analysis, in order to clarify the utility of newer markers as biological parameters or as diagnostic tools. Six patients with small cell carcinoma of the esophagus were clinicopathologically analyzed. Immunohistochemical staining was performed using primary antibodies for bombesin, CD56 and CD57 in addition to conventional endocrine markers chromogranin A, neuron specific enolase and synaptophysin. All patients died within 2 years of surgery due to cancer recurrence, whether or not they had received adjuvant therapy. Pathological stages ranged from IIa to IVb and lymph node metastasis was observed in five cases. Of the six cases, four showed a positive reaction for bombesin and five were positive for CD57. In contrast, no cases revealed a positive reaction for CD56. The one case to survive 24 months after surgery was not shown to express bombesin, CD56 or CD57. Small cell carcinoma of the esophagus demonstrated an unfavorable prognosis. The study suggested that in this disease, bombesin and CD57 (but not CD56) were useful as biological markers, predicting clinical outcome rather than having diagnostic significance.
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PMID:Small cell carcinoma of the esophagus; clinicopathological and immunohistochemical analysis of six cases. 1464 20


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