RESUMO
BACKGROUND: Insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-type 2 (HER2), and c-Met are members of the receptor tyrosine kinases (RTKs). The associations between the RTK status [protein expression and gene copy number (GCN)] and patient characteristics and between the RTK status and prognosis remain undetermined. MATERIALS AND METHODS: The study included 140 patients who underwent surgery for thymic tumors. Protein expression was evaluated by immunohistochemistry (IHC) and GCN was evaluated by bright-field in situ hybridization (BISH). The correlations between the RTK status and clinicopathological findings were examined. RESULTS: IGF-1R protein was frequently detected in thymic carcinoma (83.8%) and EGFR in thymic tumors (91.4%). Thirty-six and 39 tumors were BISH high for IGF-1R and EGFR, respectively: 28 and 25 exhibited high polysomy; 8 and 14 exhibited gene amplification. No tumor was positive for HER2 or c-Met by IHC and BISH. Multivariate analysis revealed that IGF-1R gene amplification (P = 0.027), thymic carcinoma histology, and higher tumor stage were significantly correlated with an adverse prognosis. CONCLUSIONS: Thymic epithelial tumors frequently express IGF-1R and/or EGFR proteins. IGF-1R gene amplification is suggested to define an unfavorable subset for thymic epithelial tumors.
Assuntos
Receptores ErbB/genética , Dosagem de Genes , Neoplasias Epiteliais e Glandulares/genética , Receptor IGF Tipo 1/genética , Timoma/genética , Neoplasias do Timo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/cirurgia , Proteínas Proto-Oncogênicas c-met/genética , Receptor ErbB-2/genética , Timoma/cirurgia , Neoplasias do Timo/cirurgiaRESUMO
Large cell neuroendocrine carcinoma (LCNEC) is a neuroendocrine tumor comprising a subgroup of large cell carcinoma and is a type of lung cancer showing a neuroendocrine characteristic similar to that of small cell lung carcinoma In our institution, we started to diagnose LCNEC by immunostaining in 2002, and we herein report 9 patients diagnosed with LCNEC from January 2002 to May 2008. The average patient age was 74.9, male/female ratio was 8/1, and all 9 patients had a smoking history. Pathological stages IA/IB/IIB/IIIA comprised 4/1/2/2, respectively. Peripherally located and lobulated tumors were noted on preoperative computed tomography (CT), and moderate uptake of fluoro-2-deoxy-D-glucose (FDG), which balanced with the size, was recognized on positron emission tomography (PET). All 9 patients underwent surgery and 7 underwent radical surgery. Postoperative adjuvant chemotherapy was performed for 4 patients. Three showed recurrence, and 2 of these 3 died of the primary disease. The remaining 7 patients have survived to date. The possibility of LCNEC must be considered when peripherally located lung cancer with lobulation is noted on CT and shows moderate uptake of FDG for its size on PET, and multimodal treatment is needed if the diagnosis is determined postoperatively.