Immunohistochemical profiling of receptor tyrosine kinases, MED12, and TGF-ßRII of surgically resected small cell lung cancer, and the potential of c-kit as a prognostic marker.
Oncotarget
; 8(24): 39711-39726, 2017 Jun 13.
Article
in En
| MEDLINE
| ID: mdl-28055980
ABSTRACT
The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-ßRII) by immunohistochemistry (IHC). Of the 125 evaluable samples, all tumors expressed MED12, and 123 samples (98.4%) expressed TGF-ßRII. MED12 was highly expressed in the nucleus in 92% of the positive samples while TGF-ßRII was highly expressed in the cytoplasm in 55% of the positive samples. High c-kit expression was an independent favorable prognostic marker confirmed by multivariate analysis (hazard ratio 0.543, 95% confidence interval 0.310-0.953, p = 0.033). Both the relapse free-survival and overall survival of patients who underwent adjuvant chemotherapy were statistically longer in those with high c-kit expression (n = 38) than those with intermediate, low, or no c-kit expression (n = 19) (not reached vs 11.6 months, p = 0.021; not reached vs 25.9 months, p = 0.028). IHC for c-kit may offer a prognostic marker for early-stage SCLC, and the results for MED12 and TGF-ßRII may suggest the biological characteristics of SCLC. Further investigation of the roles of their related molecules in early stage SCLC is required.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biomarkers, Tumor
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Protein Serine-Threonine Kinases
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Receptors, Transforming Growth Factor beta
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Proto-Oncogene Proteins c-kit
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Small Cell Lung Carcinoma
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Mediator Complex
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Lung Neoplasms
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
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Female
/
Humans
/
Male
Language:
En
Journal:
Oncotarget
Year:
2017
Type:
Article
Affiliation country:
Japan