RESUMEN
PURPOSE: We assessed molecular (presence of melanoma cells markers in lymph fluid [LY]) and pathological features (sentinel lymph node [SN] tumor burden according to Rotterdam criteria, metastases microanatomic location) and correlated them with survival and melanoma prognostic factors in a group of patients with positive SN biopsy. METHODS: We analyzed 368 consecutive SN-positive patients after completion lymph node dissection (CLND). In 321 patients we obtained data on SLN microanatomic location/tumor burden (only 7 cases had metastases <0.1 mm); in 137 we additionally analyzed 24-hour collected LY after CLND (multimarker reverse transcriptase-polymerase chain reaction [MM-RT-PCR] with primers for tyrosinase, MART1 (MelanA), and uMAGE mRNA (27.7% positive samples)]. Median follow-up time was 41 months. RESULTS: According to univariate analysis, the following factors had a negative impact on overall survival (OS): higher Breslow thickness (P = .0001), ulceration (P < .0001), higher Clark level (P = .008), male gender (P = .0001), metastatic lymph nodes >1 (P < .0001), nodal metastases extracapsular extension (P < .0001), metastases to additional non-SNs (P = .0004), micrometastases size ≥ 0.1 mm (P = .0006), and positive LY MM-RT-PCR (P = .0007). SN tumor burden showed linear correlation with increasing Breslow thickness (P = .01). The 5-year OS rates for SLN tumor burden <0.1 mm, 1-1.0 mm, and >1.0 mm were 84%/66%/44%, respectively, and for positive and negative LY MM-RT-PCR 47%/0%, respectively. The independent factors for shorter OS (multivariate analysis): male gender, primary tumor ulceration, number of involved nodes ≥ 4, micrometastases size >1.0 mm, and, in additional model including molecular analysis-positive MM-RT-PCR results (hazard ratio [HR] 3.2), micrometastases size >1.0 mm (HR 1.13), and primary tumor ulceration (HR 2.17). Similar results were demonstrated for disease-free survival (DFS) data. CONCLUSIONS: SN tumor burden categories according to Rotterdam criteria and the positive result of LY MM-RT-PCR assay demonstrated additional, independent prognostic value in SN-positive melanoma patients, showing significant correlation with shorter DFS and OS.
Asunto(s)
Biomarcadores de Tumor/genética , Ganglios Linfáticos/patología , Linfa/química , Melanoma/genética , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/genética , Adulto , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Antígeno MART-1/genética , Antígeno MART-1/metabolismo , Masculino , Melanoma/patología , Antígenos Específicos del Melanoma , Persona de Mediana Edad , Monofenol Monooxigenasa/genética , Monofenol Monooxigenasa/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Pronóstico , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Cutáneas/secundario , Tasa de Supervivencia , Carga TumoralRESUMEN
OBJECTIVES: The aim of the study was the analysis of women with gastrointestinal stromal tumors (GIST) of small intestine treated and followed-up in Cancer Center-Institute in Warsaw, who were primary operated in gynecological departments due to suspicion of gynecological neoplasm. MATERIALS AND METHODS: In the database of Clinical GIST Registry from 2001 to 2004 we identified 44 women with the diagnosis of CD117(+) GIST of small intestine, what corresponds to 34% (44/130) all female GIST patients. Sixteen of them (36.4%, 16/44) were primary operated on in gynecological departments due to the tentative diagnosis of gynecological neoplasm. RESULTS: The only indication for operation in 29 women was undiagnosed microscopically tumor of the pelvis. Sixteen of them (55.2%, 16/29) were operated on schedule in gynecological departments. The others 15 patients were operated due to: ileus and perforation of digestive tract (8), gastrointestinal bleeding (3), abdominal pain (2) and others (2). In analyzed group of patients 20 women (45.5%) after GIST excision remain without evidence of disease with median follow-up time of 9 months, and in 24 patients (54.5%) GIST recurred in median time of 18.5 months. In this latter group 23 patients were treated with imatinib due to inoperable/metastatic lesions. Estimated 2-year overall survival (calculated form the date of imatinib introduction) was 75%. CONCLUSIONS: GISTs, especially of small intestine, may simulate in women gynecological tumor, particularly of the ovary. Radical surgery remains the most effective method of GIST treatment. In inoperable/metastatic lesion the treatment of choice is tyrosinase kinase inhibitor--imatinib.
