Small Cell Lung Carcinoma (SCLC)

Nicholson, Siobhan; Beasley, Mary Beth; Brambilla, Elizabeth; Hasleton, Philip; Colby, Thomas V.; Sheppard, Mary N.; Falk, Roni T.; Travis, William D.

doi:10.1097/00000478-200209000-00009

Cited by 364 publications

(73 citation statements)

References 45 publications

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“…Bandoh et al 13 reported that CEA levels in the peripheral type were significantly higher than those in the central type, but no significant difference in prognosis was found between the peripheral and central types. In surgical series, no significant prognostic difference has been reported between central-type and peripheral-type tumours, 16,17 which was also demonstrated in our study. Therefore, differences in prognosis according to tumour location remain controversial.…”

Section: Discussionsupporting

confidence: 80%

“…13 However, differences in prognosis according to tumour location remain controversial. 14,16,17 Although pathological differences have not yet been well established, FDG-PET/CT can supposedly be a helpful tool in observing tumour characteristics and prognosis non-invasively, especially SCLC, where surgery is usually not indicated and direct observation of the entire tumour is unachievable.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer

Nobashi¹,

Koyasu²,

Nakamoto³

et al. 2016

BJR

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Objective: To investigate the prognostic value of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET) parameters for small-cell lung cancer (SCLC), according to the primary tumour location, adjusted by conventional prognostic factors. Methods: From 2008 to 2013, we enrolled consecutive patients with histologically proven SCLC, who had undergone FDG-PET/CT prior to initial therapy. The primary tumour location was categorized into central or peripheral types. PET parameters and clinical variables were evaluated using univariate and multivariate analysis. Results: A total of 69 patients were enrolled in this study; 28 of these patients were categorized as having the central type and 41 patients as having the peripheral type. In univariate analysis, stage, serum neuron-specific enolase, whole-body metabolic tumour volume (WB-MTV) and whole-body total lesion glycolysis (WB-TLG) were found to be significant in both types of patients. In multivariate analysis, the independent prognostic factor was found to be stage in the central type, but WB-MTV and WB-TLG in the peripheral type. Kaplan-Meier analysis demonstrated that patients with peripheral type with limited disease and low WB-MTV or WB-TLG showed significantly better overall survival than all of the other groups (p , 0.0083). Conclusion: The FDG-PET volumetric parameters were demonstrated to be significant and independent prognostic factors in patients with peripheral type of SCLC, while stage was the only independent prognostic factor in patients with central type of SCLC. Advances in knowledge: FDG-PET is a non-invasive method that could potentially be used to estimate the prognosis of patients, especially those with peripheraltype SCLC.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer

Nobashi¹,

Koyasu²,

Nakamoto³

et al. 2016

BJR

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“…2–4 Regardless of the site of origin, all SCCs progress rapidly and have a dismal prognosis. Like non-prostatic SCC, prostatic SCC shows a favorable response to systemic chemotherapy composed of etoposide and cisplatinum.…”

Section: Discussionmentioning

confidence: 99%

“…Such distinction may be difficult, because SCCs of various origins share similar histologic, immunohistochemical and ultrastructural features. 4–6 Furthermore, most prostatic SCC lose the prostate-specific immunohistochemical markers, such as prostatic acid phosphatase, PSA, prostate-specific membrane antigen, and prostein. 5 Therefore, a specific molecular marker is needed to help establish the prostatic origin of SCC.…”

Section: Introductionmentioning

confidence: 99%

TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate☆

et al. 2011

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Recent studies have shown that most prostate cancers carry the TMPRSS2-ERG gene fusion. Here we evaluated the TMPRSS2-ERG gene fusion in small cell carcinoma (SCC) of the prostate (n=12) in comparison with SCC of the urinary bladder (n=12) and lung (n=11). Florescence in situ hybridization demonstrated rearrangement of the ERG gene in 8 cases of prostatic SCC (67%), and the rearrangement was associated with deletion of the 5' ERG gene in 7 cases. But rearrangement of the ERG gene was not present in any SCC of the urinary blader or lung. Next we evaluated the TMPRSS2-ERG gene fusion in nude mouse xenografts that were derived from two prostatic SCCs carrying the TMPRSS2-ERG gene fusion. Two transcripts encoded by the TMPRSS2-ERG gene fusion were detected by RT-PCR, and DNA sequencing demonstrated that the two transcripts were composed of fusions of exon 1 of the TMPRSS2 gene to exon 4 or 5 of the ERG gene. Our study demonstrates the specific presence of TMPRSS2-ERG gene fusion in prostatic SCC, which may be helpful in distinguishing SCC of prostatic origin from non-prostatic origins. The high prevalence of the TMPRSS2-ERG gene fusion in prostatic SCC as well as adenocarcinoma implies that SCC may share a common pathogenic pathway with adenocarcinoma in the prostate.

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“…This could be due to mis-diagnosis as is fairly common in SCLC due to mixed SCLC-NSCLC histology [32], or possibly a small subset of patients whose tumors have different biology. Overall, we conclude that the SSHN is a robust molecular classifier to distinguish SCLC from other lung tumor types and normal lung across multiple gene and protein expression platforms.…”

Section: Resultsmentioning

confidence: 99%

Co-expression network analysis identifies Spleen Tyrosine Kinase (SYK) as a candidate oncogenic driver in a subset of small-cell lung cancer

et al. 2013

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BackgroundOncogenic mechanisms in small-cell lung cancer remain poorly understood leaving this tumor with the worst prognosis among all lung cancers. Unlike other cancer types, sequencing genomic approaches have been of limited success in small-cell lung cancer, i.e., no mutated oncogenes with potential driver characteristics have emerged, as it is the case for activating mutations of epidermal growth factor receptor in non-small-cell lung cancer. Differential gene expression analysis has also produced SCLC signatures with limited application, since they are generally not robust across datasets. Nonetheless, additional genomic approaches are warranted, due to the increasing availability of suitable small-cell lung cancer datasets. Gene co-expression network approaches are a recent and promising avenue, since they have been successful in identifying gene modules that drive phenotypic traits in several biological systems, including other cancer types.ResultsWe derived an SCLC-specific classifier from weighted gene co-expression network analysis (WGCNA) of a lung cancer dataset. The classifier, termed SCLC-specific hub network (SSHN), robustly separates SCLC from other lung cancer types across multiple datasets and multiple platforms, including RNA-seq and shotgun proteomics. The classifier was also conserved in SCLC cell lines. SSHN is enriched for co-expressed signaling network hubs strongly associated with the SCLC phenotype. Twenty of these hubs are actionable kinases with oncogenic potential, among which spleen tyrosine kinase (SYK) exhibits one of the highest overall statistical associations to SCLC. In patient tissue microarrays and cell lines, SCLC can be separated into SYK-positive and -negative. SYK siRNA decreases proliferation rate and increases cell death of SYK-positive SCLC cell lines, suggesting a role for SYK as an oncogenic driver in a subset of SCLC.ConclusionsSCLC treatment has thus far been limited to chemotherapy and radiation. Our WGCNA analysis identifies SYK both as a candidate biomarker to stratify SCLC patients and as a potential therapeutic target. In summary, WGCNA represents an alternative strategy to large scale sequencing for the identification of potential oncogenic drivers, based on a systems view of signaling networks. This strategy is especially useful in cancer types where no actionable mutations have emerged.

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Small Cell Lung Carcinoma (SCLC)

Cited by 364 publications

References 45 publications

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer

TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate☆

Co-expression network analysis identifies Spleen Tyrosine Kinase (SYK) as a candidate oncogenic driver in a subset of small-cell lung cancer

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