RESUMO
BACKGROUND: EGFR and VEGFR2 protein expressions are hallmarks of clear cell renal cancer (RCC) with questionable prognostic impact. The skeletal system is one of the most common metastatic sites of RCC. Unfortunately, there are no data for EGFR and VEGFR2 protein expression in such lesions. MATERIALS AND METHODS: Twenty cases of bone metastatic clear cell RCC were analyzed. EGFR and VEGFR2 proteins were detected by immunohistochemistry and analyzed by morphometry scoring both % positivity and the intensity. RESULTS: EGFR protein scores were significantly reduced in bone metastases of RCC due to the reduction of EGFR protein expression in about one third of the cases (7/20). The VEGFR2 protein-positive phenotype of clear cell RCC was relatively frequent (7/20, 35%), but was lost in bone metastases (2/20, 10%). CONCLUSION: These data suggest a phenotypic/genotypic change of clear cell RCC during the progression to bones and warrant further investigation.
Assuntos
Adenocarcinoma de Células Claras/enzimologia , Neoplasias Ósseas/embriologia , Neoplasias Ósseas/secundário , Carcinoma de Células Renais/enzimologia , Receptores ErbB/biossíntese , Neoplasias Renais/enzimologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Adenocarcinoma de Células Claras/patologia , Idoso , Carcinoma de Células Renais/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Bone metastasis is a frequent complication of lung cancer progression, however, studies on bone metastatic tissues are scanty. Here we have collected a small cohort of 11 non-small cell lung cancer cases where primary tumors and corresponding bone metastases were available for pathological analysis. We have tested two molecular markers: EGFR protein expression and K-RAS mutation at codon 12 using immunohistochemistry and RFLPPCR, respectively. We have shown that using improved protocols, EGFR protein (both the extracellular as well as the cytoplasmic domain) is readily detectable in decalcified bone tissue. We found that the EGFR expression status is highly similar in bone metastases compared to the primary tumors, although the expression levels may change. Individual comparison of corresponding primary and metastatic NSCLC tissues indicated that downregulation of EGFR was a rare event (2/11) compared to upregulation (4/11) in bone metastases. On the other hand, our data indicate that the K-RAS mutational status of the primary tumor does not predict the status of the bone metastatic tissue of NSCLC, since we have observed both emergence of mutant clones in metastases from wild-type (wt) primary tumors and loss of mutant clones in metastases from mutant primaries in addition to the maintained mutant status. Our data support that at least two progression models occur in NSCLC, the samegene as well as the clonal selection one. It is noteworthy that in NSCLC cases with wt- or mutant KRAS, downregulation of EGFR expression was a rare event although upregulation in bone metastases was observed more frequently in wt K-RAS cases.
Assuntos
Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Receptores ErbB/metabolismo , Genes ras/genética , Neoplasias Pulmonares/patologia , Mutação/genética , Fenótipo , Idoso , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Progressão da Doença , Regulação para Baixo , Receptores ErbB/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Regulação para CimaRESUMO
The genotype of breast cancer (BRC) is considered to be relatively stable during tumor progression, accordingly, determination of the estrogen receptor and HER-2/neu status is currently based on the primary tumor. However, recent data suggest that the gene expression profile of the metastatic lesion can be different compared to that of the primary BRC. Accordingly, it is possible that the HER-2/neu status is different in the metastatic lesion and the primary BRC. Since the bone is the most frequent metastatic site during the progression of BRC, we have analyzed the HER-2/neu status of 48 bone metastatic BRC cases by immunohistochemistry and fluorescent in situ hybridization, and it was possible to compare it to the primary site in 23 cases. The frequency of HER-2/neu amplification of BRC in the primary tumors was found to be 17.4% compared to 10.5% in bone metastases. Half of BRC cases with HER-2/neu amplification lost this genotype in bone metastases (4/23 versus 2/23, respectively) and even in the 2 cases where HER-2/neu amplification was retained in the metastases, the copy number was found to be decreased compared to the primary tumor. Based on our data and previous reports in the literature, we suggest to perform HER-2/neu testing both on primary tumor and samples obtained from BRC metastases, at least in case of primary tumors with HER-2/neu amplification, before introduction of HER-2/neu-targeting therapy.