RESUMO
INTRODUCTION: Molecular apocrine (MA) tumors are estrogen receptor (ER) negative breast cancers characterized by androgen receptor (AR) expression. We analyzed a group of 58 transcriptionally defined MA tumors and proposed a new tool to identify these tumors. METHODS: We performed quantitative reverse transcription PCR (qRT-PCR) for ESR1, AR, FOXA1 and AR-related genes, and immunohistochemistry (IHC) for ER, PR, Human Epidermal Growth Factor Receptor 2 (HER2), CK5/6, CK17, EGFR, Ki67, AR, FOXA1 and GCDFP15 and we analyzed clinical features. RESULTS: MA tumors were all characterized by ESR1(-) AR(+) FOXA1(+) and AR-related genes positive mRNA profile. IHC staining on these tumors showed 93% ER(-), only 58% AR(+) and 90% FOXA1(+). 67% and 57% MA tumors were HER2(3+) and GCDFP15(+), respectively. Almost all MA tumors (94%) had the IHC signature HER2(3+) or GCDFP15(+) but none of the 13 control basal-like (BL) tumors did. Clinically, MA tumors were rather aggressive, with poor prognostic factors. CONCLUSION: MA tumors could be better defined by their qRT-PCR-AR profile than by AR IHC. In addition, we found that HER2 or GCDFP15 protein overexpression is a sensitive and specific tool to differentiate MA from BL in the context of ER negative tumors. A composite molecular and IHC signature could, therefore, help to identify MA tumors in daily practice.
Assuntos
Neoplasias da Mama/genética , Proteínas de Transporte/biossíntese , Glicoproteínas/biossíntese , Proteínas de Neoplasias/biossíntese , Receptor ErbB-2/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Glândulas Apócrinas/metabolismo , Glândulas Apócrinas/patologia , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Proteínas de Transporte/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/genética , Humanos , Proteínas de Membrana Transportadoras , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores Androgênicos/biossíntese , Receptores de Estrogênio/biossínteseRESUMO
PURPOSE: To prospectively analyze the evolution of hepatic and peritoneal unresectable metastases from gastrointestinal stromal tumors (GIST) under imatinib mesylate, a new targeted treatment, which induces changes in lesion structure. MATERIALS AND METHODS: 54 patients with metastases from GIST underwent an abdominal and pelvic computed tomography examination without and with contrast enhancement, before and during treatment with imatinib mesylate. The number and size of lesions and contrast enhancement were noted before treatment and every 2 weeks for the first 2 months, then every 2 months for the first year of treatment and every 3 months thereafter. RESULTS: 27 patients presented with both hepatic and peritoneal metastases, 14 had only peritoneal and 13, only hepatic disease. On baseline imaging, all metastases were hypodense heterogeneous lesions with progressive, concentric enhancement. After treatment (mean duration of follow-up: 23 months) metastases decreased in size number and enhancement in 35/54 patients, remained stable in 2 patients and increased in 14 patients. In 13/39 patients with hepatic metastases a cyst-like appearance was noted. Reactivation after a partial response appeared first as a focal, peripheral, solid nodule in the wall of a cystic lesion, or an increase in lesion density, before size regrew. CONCLUSION: Besides the classic size criterion, a decrease in density and in contrast enhancement with stable "near cystic" lesions signifies a good response. A more aggressive approach (surgery or radiofrequency ablation) may be indicated for initially focal recurrences with a stable size.
Assuntos
Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Tomografia Computadorizada por Raios X , Adulto , Idoso , Benzamidas , Meios de Contraste , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Iohexol , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: To define computed tomography (CT) criteria for evaluating the response of patients with gastrointestinal stromal tumors (GIST) who are receiving Imatinib (tyrosine-kinase inhibitor therapy). MATERIALS AND METHODS: This prospective CT study evaluated 107 consecutive patients with advanced metastatic GIST treated with Imatinib. RESULTS: Seventy patients had total or partial cystic-like transformation of hepatic and/or peritoneal metastases. These pseudocysts remained unchanged in size or stable in size on successive CT examinations (stable disease according to RECIST criteria). Forty-six patients developed metastases, 17 patients showed increasing parietal thickness and 29 patients with peripheral enhancing nodules. These CT changes represented local recurrence consistent with GIST resistance to Imatinib treatment. WHO or RECIST criteria did not provide a reliable evaluation of disease evolution or recurrence. Development of new enhancement of lesions (parietal thickness or nodule) was the only reliable criterion. CONCLUSION: The development of peripheral thickening or enhancing nodules within cystic-like metastatic lesions, even without any change in size, represented progressive GIST under Imatinib, growing in a short time and should alert the clinician for the possible need for a change in therapy.