Neuroendocrine and biologic features of primary tumors and tissue in pulmonary large cell carcinomas

Saber, Alexandre M Ab'; Neto, Ledo Mazzei Massoni; Bianchi, Cristina P; Ctenas, Bruno; Parra, Edwin Roger; Eher, Esmeralda Miristeni; Pereira, João Carlos das Neves; Takagaki, Teresa Yae; Yamaguchi, Nagamassa; Capelozzi, Vera Luíza

doi:10.1016/j.athoracsur.2003.11.047

Cited by 22 publications

(8 citation statements)

References 17 publications

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“…Thus, SCG3 transcript may also be able to identify those patients with neuroendocrine NSCLC and CTC. Although the clinical significance of neuroendocrine differentiation in NSCLC remains contentious, some recent studies report a worse prognosis (41,42).…”

Section: Discussionmentioning

confidence: 99%

SCG3 Transcript in Peripheral Blood Is a Prognostic Biomarker for REST-Deficient Small Cell Lung Cancer

Moss

Jacobson²,

Walker³

et al. 2008

Clinical Cancer Research

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Purpose: Specific markers of circulating tumor cells may be informative in managing lung cancer.Because the RE-1silencing transcription factor (REST/NRSF) is a transcriptional repressor that is inactivated in neuroendocrine lung cancer, we identified REST-regulated transcripts (CHGA, CHGB, SCG3,VGF, and PCSK1) for evaluation as biomarkers in peripheral blood. Experimental Design: Transcripts were screened across lung cancer and normal cell lines. Candidates were assessed by reverse transcription-PCR and hybridization of RNA extracted from the peripheral blood of 111 lung cancer patients obtained at clinical presentation and from 27 cancer-free individuals. Results: Expression profiling revealed multiple chromogranin transcripts were readily induced on RESTdepletion, most notably SCG3 was induced >500-fold.The SCG3 transcript was also overexpressed by 12,000-fold in neuroendocrine compared with nonneuroendocrine lung cancer cells. In peripheral blood of lung cancer patients and cancer-free individuals, we found that SCG3 was more tumor-specific and more sensitive than other chromogranin transcripts as a biomarker of circulating tumor cells. Overall, 36% of small cell lung cancer (SCLC) and 16% of non-SCLC patients scored positively for normalized SCG3 transcript. This correlated with worse survival among SCLC patients with limited disease (n = 33; P = 0.022) but not extensive disease (n = 29; P = 0.459). Interestingly, the subcohort of 6 SCLC patients with resistance to platinum/ etoposide chemotherapy all scored positively for peripheral blood SCG3 transcript (P = 0.022). Conclusions: SCG3 mRNA, a component of the REST-dependent neurosecretory transcriptional profile, provides a sensitive prognostic biomarker for noninvasive monitoring of neuroendocrine lung cancer.

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Section: Discussionmentioning

confidence: 99%

SCG3 Transcript in Peripheral Blood Is a Prognostic Biomarker for REST-Deficient Small Cell Lung Cancer

Moss

Jacobson²,

Walker³

et al. 2008

Clinical Cancer Research

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show abstract

“…The presence of neuroendocrine differentiation detected on an ultrastructural or molecular level, is in fact a predictor of an aggressive clinical course [32][33][34]. Even in patients with stage I lung cancer that is potentially resectable the prognosis is poor.…”

Section: Prognosismentioning

confidence: 99%

Large cell/neuroendocrine carcinoma

Gollard¹,

Jhatakia²,

Elliott³

et al. 2010

Lung Cancer

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“…At the cellular level, LCNEC has a higher proliferative rate compared to LCC. A study from Ab'Saber et al 17 found that LCNEC had greater staining than LCC for p21 waf1/cip1 , which is involved in the regulation of apoptosis and the cell cycle, as well as microvessel density, a marker of angiogenesis. Patients found to have greater than 3.5% staining for p21 waf1/cip1 and microvessel density staining of greater than 3.0% in their tumor specimens were found to be at high risk of death due to lung cancer.…”

Section: Molecular Biologymentioning

confidence: 99%