Gene network analyses point to the importance of human tissue kallikreins in melanoma progression.

BACKGROUND: A wide variety of high-throughput microarray platforms have been used to identify molecular targets associated with biological and clinical tumor phenotypes by comparing samples representing distinct pathological states. METHODS: The gene expression profiles of human cutaneous melanomas were determined by cDNA microarray analysis. Next, a robust analysis to determine functional classifications and make predictions based on data-oriented hypotheses was performed. Relevant networks that may be implicated in melanoma progression were also considered. RESULTS: In this study we aimed to analyze coordinated gene expression changes to find molecular pathways involved in melanoma progression. To achieve this goal, ontologically-linked modules with coordinated expression changes in melanoma samples were identified. With this approach, we detected several gene networks related to different modules that were induced or repressed during melanoma progression. Among them we observed high coordinated expression levels of genes involved in a) cell communication (KRT4, VWF and COMP); b) epidermal development (KLK7, LAMA3 and EVPL); and c) functionally related to kallikreins (EVPL, KLK6, KLK7, KLK8, SERPINB13, SERPING1 and SLPI). Our data also indicated that hKLK7 protein expression was significantly associated with good prognosis and survival. CONCLUSIONS: Our findings, derived from a different type of analysis of microarray data, highlight the importance of analyzing coordinated gene expression to find molecular pathways involved in melanoma progression.

Sentinel lymph node biopsy in cutaneous melanoma: analysis of 240 consecutive cases.

BACKGROUND: The objective of this study was to evaluate practical rules for sentinel lymph node biopsy for melanoma and discuss the indications and outcomes of 240 patients. METHODS: A prospective, nonrandomized analysis was performed on 240 patients in a referral cancer center. The median patient age was 51 years, and the median Breslow thickness was 1.60 mm. Ulceration was found in 30.4 percent of the cases. The median follow-up was 27.81 months. The sentinel lymph node biopsy was performed in 240 patients with cutaneous melanoma thicker or equal to 1 mm. The operation was performed with preoperative lymphoscintigraphy and postoperative immunohistochemistry. A statistical analysis was performed comparing the need for a gamma probe in each location, the value of the experience, the need for immunohistochemistry, positivity compared with Breslow thickness, reasons for the success of the lymph node localization, and evolution. RESULTS: A total of 263 lymph node basins were identified (160 in the axilla, 86 in the inguinal region, and 17 in less common locations, including the popliteal, epitrochlear, and cervical regions). In every lymph node basin, the success of localization was directly related to use of the probe. The success rate for finding the sentinel lymph node increased year by year. Lymph node analysis disclosed positivity of 12.5 percent with hematoxylin and eosin staining and 17.5 percent with immunohistochemistry (excluding the sentinel lymph node not found disclosed 13.2 percent with hematoxylin and eosin and 18.5 percent with HMB45). Immunohistochemistry increased positivity by 40 percent. Positivity was directly related to Breslow thickness (p < 0.001). CONCLUSIONS: This study shows the importance of the gamma probe in all lymph node basins but mainly in the axilla and unusual basins, as well as the importance of experience and immunohistochemistry. As a new procedure, it was possible to recognize the pattern of recurrence in the follow-up.