Factors associated with false-negative sentinel lymph node biopsy in melanoma patients.

INTRODUCTION: Some melanoma patients who undergo sentinel lymph node (SLN) biopsy will have false-negative (FN) results. We sought to determine the factors and outcomes associated with FN SLN biopsy. METHODS: Analysis was performed of a prospective multi-institutional study that included patients with melanoma of thickness > 1.0 mm who underwent SLN biopsy. FN results were defined as the proportion of node-positive patients who had a tumor-negative sentinel node biopsy. Kaplan-Meier survival analysis and univariate and multivariate analyses were performed. RESULTS: This analysis included 2,451 patients with median follow-up of 61 months. FN, true-positive (TP), and true-negative (TN) SLN results were found in 59 (10.8%), 486 (19.8%), and 1,906 (77.8%) patients, respectively. On univariate analysis comparing the FN with TP groups, respectively, the following factors were significantly different: age (52.6 vs. 47.6 years, p = 0.004), thickness (mean 2.1 vs. 3.1 mm, p = 0.003), lymphovascular invasion (LVI; 3.7 vs. 13.7%, p = 0.037), and local/in-transit recurrence (LITR; 32.2 vs. 12.4%, p < 0.0001); these factors remained significant on multivariate analysis. Overall 5-year survival was greater in the TN group (86.7%) compared with the TP (62.3%) and FN (51.3%) groups (p < 0.0001); however, there was no significant difference in overall survival comparing the TP and FN groups (p = 0.32). CONCLUSIONS: This is the largest study to evaluate FN SLN results in melanoma, with a FN rate of 10.8%. FN results are associated with greater patient age, lower mean thickness, less frequent LVI, and greater risk of LITR. However, survival of patients with FN SLN is not statistically worse than that of patients with TP SLN.

Molecular classification of melanoma using real-time quantitative reverse transcriptase-polymerase chain reaction.

BACKGROUND: The early detection and characterization of metastatic melanoma are important for prognosis and management of the disease. Molecular methods are more sensitive in detecting occult lymph node metastases compared with standard histopathology and are reported to have utility in clinical diagnostics. METHODS: Using real-time quantitative reverse transcriptase-polymerase chain reaction ([q]RT-PCR), the authors examined 36 samples (30 melanomas, 4 benign nevi, and 2 reactive lymph nodes) for the expression of 20 melanoma-related genes that function in cell growth and differentiation (epidermal growth factor receptor [EGFR], WNT5A, BRAF, FOS, JUN, MATP, and TMP1), cell proliferation (KI-67, TOP2A, BUB1, BIRC5, and STK6), melanoma progression (CD63, MAGEA3, and GALGT), and melanin synthesis (TYR, MLANA, SILV, PAX3, and MITF). In addition, samples were tested for mutations in BRAF (exons 11 and 15) and NRAS (exons 2 and 3). RESULTS: Hierarchical clustering analysis of the expression data was able to distinguish between the melanoma and nonmelanoma samples and further stratified the melanoma samples into two groups differentiated by high expression of the genes involved in beta-catenin activation (EGFR and WNT5A) and the MAPK/ERK pathway (BRAF, FOS, and JUN). Eighteen of the 28 patients (64%) were found to have mutations in either exon 15 of BRAF (V599 substitution) or codon 61 of NRAS. The mutations were mutually exclusive and did not appear to be associated with the different expression subtypes. CONCLUSIONS: The results of the current study demonstrate that real-time qRT-PCR can be analyzed using hierarchical clustering to identify expression patterns that differentiate between melanomas and other tissue types. Using a supervised analysis of the data, the authors found that the best discriminators for molecularly distinguishing between melanoma, benign nevi, and lymph nodes were MLANA, CD63, and BUB1. These markers could have diagnostic utility for the detection of melanoma micrometastasis in sentinel lymph nodes.

Preoperative lymphoscintigraphy for breast cancer does not improve the ability to identify axillary sentinel lymph nodes.

OBJECTIVE: To evaluate the role of preoperative lymphoscintigraphy in sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Numerous studies have demonstrated that SLN biopsy can be used to stage axillary lymph nodes for breast cancer. SLN biopsy is performed using injection of radioactive colloid, blue dye, or both. When radioactive colloid is used, a preoperative lymphoscintigram (nuclear medicine scan) is often obtained to ease SLN identification. Whether a preoperative lymphoscintigram adds diagnostic accuracy to offset the additional time and cost required is not clear. METHODS: After informed consent was obtained, 805 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study, a multiinstitutional study involving 99 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Preoperative lymphoscintigraphy was performed at the discretion of the individual surgeon. Biopsy of nonaxillary SLNs was not required in the protocol. Chi-square analysis and analysis of variance were used for statistical comparison. RESULTS: Radioactive colloid injection was performed in 588 patients. In 560, peritumoral injection of isosulfan blue dye was also performed. A preoperative lymphoscintigram was obtained in 348 of the 588 patients (59%). The SLN was identified in 221 of 240 patients (92.1%) who did not undergo a preoperative lymphoscintigram, with a false-negative rate of 1.6%. In the 348 patients who underwent a preoperative lymphoscintigram, the SLN was identified in 310 (89.1%), with a false-negative rate of 8.7%. A mean of 2.2 and 2. 0 SLNs per patient were removed in the groups without and with a preoperative lymphoscintigram, respectively. There was no statistically significant difference in the SLN identification rate, false-negative rate, or number of SLNs removed when a preoperative lymphoscintigram was obtained. CONCLUSIONS: Preoperative lymphoscintigraphy does not improve the ability to identify axillary SLN during surgery, nor does it decrease the false-negative rate. Routine preoperative lymphoscintigraphy is not necessary for the identification of axillary SLNs in breast cancer.