Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-small cell lung cancers with neuroendocrine differentiation (NSCLC-NE) may demonstrate biologic behavior intermediate between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with impact on prognosis. We studied the expression of four well-defined neuroendocrine (NE) markers: neuron-specific enolase (NSE), chromogranin A, Leu-7, gastrin-releasing peptide, and a panel of three non-NE markers, including vimentin, and the epithelial markers carcino-embryonic antigen (CEA) by immunohistochemistry, and mucin by histochemistry in 237 resected NSCLCs from patients on six LCSG protocols. Twenty-nine (12%) tumors were positive for 2 or more NE markers. An NE differentiation score was calculated but failed to correlate with recurrence as did other combinations of markers. However, the presence of tissue staining for CEA was strongly associated with improved survival (p = 0.011), whereas the presence of mucin was associated with a worse outcome (p < 0.001). Individually, CEA and mucin remained prognostic even when corrected for stage, histologic features, and performance status. We conclude that NE differentiation is not predictive of recurrence in patients with resected NSCLC but data on patterns of CEA and mucin expression may improve prognostication and permit rational design of new therapeutic approaches.
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PMID:Impact of neuroendocrine differentiation in non-small cell lung cancer. The LCSG experience. 798 66

Non-small cell lung cancer with neuroendocrine differentiation may represent a subset of patients with a more aggressive (like small cell lung cancer) or less aggressive (like carcinoid) biological behavior. To investigate their prognostic significance, immunohistochemical stains for 4 neuroendocrine markers (neuron-specific enolase, chromogranin A, Leu-7, and synaptophysin) and carcinoembryonic antigen (CEA) were studied in 260 patients with surgically resected stage I and II non-small cell lung cancer. The following percentages of cases were positive for each marker: neuron-specific enolase, 70.0%; chromogranin A, 14.2%; Leu-7, 7.7%; synaptophysin, 11.2%; and CEA, 68.5%. Sixty-one (23.5%) were positive for > or = 2 neuroendocrine markers. When compared to adenocarcinoma, squamous cell carcinoma displayed lower positivity for CEA and > or = 2 neuroendocrine markers. There was no significant difference in stage, site of relapse (distant versus local), disease-free, or overall survival for each marker individually or for those with > or = 2 neuroendocrine markers. Multivariate analysis showed that higher nodal stage (N1 versus N0), tumor stage (T2 versus T1), older age, and the presence of mucin predicted for poorer overall survival. Neuroendocrine markers and CEA were not of prognostic significance in this group of patients with resected stage I and II non-small cell lung cancer.
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PMID:The prognostic significance of neuroendocrine markers and carcinoembryonic antigen in patients with resected stage I and II non-small cell lung cancer. 818 76

IA-1 is a recently isolated novel complementary DNA which encodes a protein of 510 amino acids that contains both a zinc finger DNA-binding domain and a putative prohormone domain. mRNA expression of IA-1 has been found thus far only in tumors of neuroendocrine origin. In this report we describe the expression of IA-1 mRNA in a panel of 64 human lung cancer cell lines. IA-1 mRNA was detected by Northern blot analysis in 97% (30 of 31) of small cell lung cancer cell lines. In contrast, IA-1 mRNA was detected in only 13% (4 of 30) of non-small cell lung cancer cell lines. Nine of the 30 (30%) expressed either chromogranin A mRNA or produced L-dopa decarboxylase. Four of these 9 (44%) had detectable levels of IA-1 mRNA. In most of the lung cancer cell lines examined, IA-1 showed high concordance with the other neuroendocrine markers, L-dopa decarboxylase, and chromogranin A. The one exception was a variant small cell lung cancer cell line which expressed low or nondetectable levels of L-dopa decarboxylase. IA-1 is a candidate marker of neuroendocrine differentiation of human lung tumors.
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PMID:IA-1, a new marker for neuroendocrine differentiation in human lung cancer cell lines. 836 10

Levels of the tumour markers neurone specific enolase (NSE), lactate dehydrogenase (LDH), chromogranin A (ChrA) and carcinoembryonic antigen (CEA) were measured in serum taken at presentation and during treatment, remission and relapse from 154 patients who received chemotherapy for small cell lung cancer at a single centre over a 6 year period. At presentation NSE was the most frequently elevated marker, being raised in 81% of patients and significantly higher in extensive as opposed to limited disease, as were LDH and ChrA. The response rate to therapy was best correlated with presentation level of ChrA, being 79% for those whose levels were within twice the upper limit of normal and 51% above (P < 0.01). Multivariate regression analysis showed NSE, performance status and albumin at presentation to be the best independent predictors of survival. Patients with NSE below twice the upper limit of normal, Karnofsky performance status of 80 or above and albumin 35 g l-1 or above had a median survival of 15 months with 25% alive at 2 years, whilst those with NSE above twice normal, Karnofsky below 80 and albumin less that 35 g l-1 had all died by 8 months. Changes in marker levels during therapy were of low predictive value for outcome although the finding of rising NSE during chemotherapy after an initial fall correlated with significantly reduced duration of remission. There was a strong inverse correlation between the NSE level at the time of response and duration of remission (P < 0.0001). Prediction of relapse was most reliable with ChrA, 52% of patients having rising levels before clinical evidence of disease recurrence.
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PMID:Tumour markers for prediction of survival and monitoring of remission in small cell lung cancer. 838 78

For determination of the cellular distribution of bcl-2 expression in lung cancer and clarification of its correlation with cell neuroendocrine differentiation, Bcl-2 immunostaining was carried out on a large series of formalin-fixed, paraffin-embedded lung cancer samples, and four general neuroendocrine marker and seven peptide hormone stainings were carried out on all Bcl-2-positive squamous cell carcinomas and adenocarcinomas of the lung as well as on 8 pulmonary neuroendocrine carcinomas histologically diagnosed. In addition, 3 small cell lung cancer cell lines were studied by Western blotting. Neuroendocrine differentiation in Bcl-2-negative squamous cell carcinomas and adenocarcinomas was examined with chromogranin A and alpha-subunit of Go protein stainings. Bcl-2 protein was detected in 104/111 small cell carcinomas, 8/8 neuroendocrine carcinomas, 0/6 typical (well differentiated) carcinoids, 23/64 squamous cell carcinomas, 4/65 adenocarcinomas, and all 3 small cell lung cancer cell lines. All 8 neuroendocrine carcinomas, 11 of the Bcl-2-positive squamous cell carcinomas, and all 4 Bcl-2 positive adenocarcinomas expressed multiple neuroendocrine markers. The distributions of Bcl-2 and neuroendocrine marker immunoreactivity closely paralleled each other on consecutive sections. In squamous cell carcinomas, Bcl-2-positive cells could be roughly subdivided into those with neuroendocrine differentiation features, usually demonstrating intense Bcl-2 staining, with basaloid tumor cells usually expressing weak to moderate Bcl-2 staining. The present study clearly shows Bcl-2 protein expression to be remarkably differentially regulated according to histological types of lung cancers and to appear to quite likely be closely associated with neuroendocrine differentiation of tumor cells, indicating that bcl-2 is importantly involved in cell development and differentiation, in addition to protecting cells from apoptosis. Bcl-2 might be usable as a neuroendocrine marker in lung cancers and possibly also in neural-crest-derived tumors.
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PMID:Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation. 877 38

Two small cell lung cancer (SCLC) cell lines have been established from malignant effusions obtained from an SCLC patient with hypercalcemia during a 3-month follow-up period. The two cell lines established were shown to transcribe the parathyroid hormone-related protein (PTHrP) gene and to constantly secrete fairly large amounts of PTHrP into the culture medium. The efficiency of PTHrP gene transcription and secretion was greater in the cell line established in the late stage (KOT-2) as compared with that obtained in the early stage (KOT-1). Immunohistochemical studies showed that these cells also coexpress neuroendocrine (NE) products such as chromogranin A and neuron-specific enolase (NSE).
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PMID:Establishment of two human small cell lung cancer cell lines: the evidence of accelerated production of parathyroid hormone-related protein with tumor progression. 956 9

Recent reports indicate that Small Cell Lung Cancer (SCLC) responds favorably to chemotherapy, and this response is associated with the expression of neuroendocrine (NE) markers. However, the currently available reports on the expression of NE markers in SCLC and Non-Small Cell Lung Cancer (NSCLC) are highly inconsistent and need to be reevaluated. Therefore, we have undertaken the current study to clearly define the expression of NE markers in SCLC and NSCLC using representative cell lines. We studied the NE markers, chromogranin A, Neuron specific enolase (NSE), Leu-7 and synaptophysin using various immunochemical and molecular biological methods. By employing Western blotting method, we found that both SCLC and NSCLC cells express large amounts of NSE and chromogranin A. The natural killer cell surface associated antigen (Leu-7) was expressed specifically only by SCLC cell lines. This finding was further confirmed by immunofluorescence staining of the SCLC cells. We could not detect any synaptophysin levels in any of the above cell types by Western blotting technique. Therefore, we employed reverse transcription polymerase chain reaction (RT.PCR) to study the expression of synaptophysin mRNA and found that both SCLC and NSCLC cells express it, albeit in different amounts.
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PMID:Expression of neuron-specific enolase, chromogranin A, synaptophysin and Leu-7 in lung cancer cell lines. 970 May 77

A new human cancer cell line was established from a metastatic lesion of a small cell lung carcinoma (SCLC-R1) and maintained in continuous culture with a doubling time of 62 h. The SCLC-R1 line, whose ultrastructural features are presented, showed a diploid DNA content, a translocation involving chromosome 16 [t(16;?)(q24;?)] and noticeable deletions in the FHIT (fragile histidine triad) region in the short arm of chromosome 3 [del(3)(p14)] and in the telomeric region of the short arm of chromosome 12 [del(12)(p13)]. The involvement of 12p in metastatic small cell lung cancer is reported here for the first time. No amplification or rearrangements were evident in the c-myc, L-myc, N-myc, int-2, c-erbB-2, H-ras, K-ras, c-mos, and hst-1 genes by Southern blot analysis. Wild-type p53, RB, K-ras and H-ras genes were evident by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. The neuron specific enolase (NSE) level was much higher in the cell line's cytosol than in the patient's serum and the cell line also had high expression of chromogranin A and cytokeratin 19. SCLC-R1 cells were sensitive to cisplatin, carboplatin and doxorubicin. The clinical history of the patient from whom the cell line was derived is reported. The characteristics of this new cell line indicate it to be a useful experimental model to investigate lung cancer biology and anticancer drug response.
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PMID:Chromosomal alterations, biological features and in vitro chemosensitivity of SCLC-R1, a new cell line from human metastatic small cell lung carcinoma. 971 81

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

The aims of our work were 1) to determine the diagnostic performance of an immunoradiometric assay of chromogranin A (CgA) in small cell lung cancer and 2) to compare its discriminatory power with that of neuron-specific enolase (NSE), the marker currently used for SCLC. We selected 166 cases of small cell (64) and non-small cell (102) lung cancer and 106 cases of non-malignant lung diseases as controls. Both CgA and NSE were assayed by immunoradiometric methods and cutoff values were established on the basis of a pre-fixed specificity of 95% in non-malignant lung diseases. The CgA assay showed better diagnostic sensitivity than NSE in SCLC (61% versus 57%), especially in limited disease, and a low positivity rate in NSCLC with respect to NSE (14% versus 22%). By contrast, NSE reflected disease extent more accurately than CgA (U test: CgA p<0.05, NSE p<0.001). Finally, we found that the CgA assay was not affected by hemolysis whereas NSE serum levels greatly increased in hemolyzed sera. In conclusion, CgA assaying by an IRMA method is a reliable procedure in the diagnosis of SCLC. NSE remains the marker of choice in staging and monitoring of the disease. Further studies are needed to evaluate the prognostic significance of the marker and its role in therapy monitoring and patient follow-up.
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PMID:Immunoradiometric assay of chromogranin A in the diagnosis of small cell lung cancer: comparative evaluation with neuron-specific enolase. 1128 56


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