Molecular clonality of in-transit melanoma metastasis

In-transit melanoma is characterized by an aggressive pattern of recurrence that is associated with a poorer prognosis. Because in-transit melanoma is considered to result from the intralymphatic trapping of melanoma cells be tween the primary tumor and regional lymph nodes, it provides an excellent model to assess genetic events associated with early metastasis, The hypoth esis of this study was to determine whether in-transit metastases are clona l in origin and therefore, may have specific genetic alterations uniquely a ssociated with this disease and the development of early metastasis, This w as assessed using loss of heterozygosity (LOH) analysis for specific DNA mi crosatellite loci. Seventy-nine paraffin-embedded in-transit melanoma lesio ns from 25 patients (range, 2 to 9 lesions per patient; average, 3.4 lesion s per patient) were assessed for LOH using eight microsatellite DNA markers on six chromosomes. In 19 of 25 patients (76%) LOH was demonstrated for at least one marker. The most frequent microsatellite marker demonstrating IX )H was D9S157 (56%). Using LOH microsatellite markers to assess intertumor heterogeneity, six of 79 tumors (7.6%) demonstrated different profiles when compared to other lesions from the same patient, In-transit metastases fro m those patients demonstrating intertumor heterogeneity were further assess ed using Laser capture microdissection and DNA analysis, and revealed no si gnificant intratumor heterogeneity, In conclusion, LOH was frequently obser ved in in-transit melanoma metastasis, Based on LOH analysis, in-transit me tastases are clonal in origin The establishment of clinically successful in -transit melanoma metastasis requires specific genetic events that seem to be unique and homogeneous for each patient.