Gene Expression May Help Predict Sentinel Lymph Node Positivity in Melanoma Patients

By exploring gene expression variables in addition to clinicopathologic variables, researchers were able to better predict which patients with melanoma would have sentinel lymph node (SLN) biopsy positivity, according to the results of a study published in the Journal of Clinical Oncology.

“Data obtained by gene expressing profiling can be combined with Breslow depth, tumor ulceration, and patient age to calculate the predicted probability of SLN positivity at the time of primary diagnosis,” wrote study author Alexander Meves, MD, of Mayo Clinic, Rochester, Minnesota, and colleagues. “These data have the potential to improve patient care by avoiding unnecessary SLN procedures.”

According to the background information in the study, less than one-fifth of patients with melanoma who undergo SLN biopsy have positive results. Because of this, attempts are being made to improve the identification of patients at risk for SLN metastases.

In this study, Meves and colleagues conducted a multi-institutional study looking at molecular risk factors that may be linked with SLN positivity. They used next-generation sequencing validated with quantitative polymerase chain reaction to test 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases and discover possible gene clusters associated with metastasis.

“ITGB3 and SRC, a key downstream effector of β3 integrin, formed the center of a functional network deregulated in regionally metastatic vs nonmetastatic melanoma,” the researchers wrote.  

Meves and colleagues used polymerase chain reaction to quantify gene expression in a cohort of 360 consecutive melanomas. Their analysis showed that younger age, tumor ulceration, and greater Breslow depth increased likelihood of nodal metastasis detected by SLN within 90 days of diagnosis. Four genes were identified that distinguished patients with SLN positivity: ITGB3, LAMB1, PLAT, and TP53.

“The likelihood of a nodal metastasis by SLN within 90 days of primary diagnosis was significantly decreased for patients in whom RNA copy numbers were as follows: ITGB3 10, TP53 more than 50, and neither LAMB1 more than 250 or PLAT more than 427,” the researchers explained.

Next, the researchers developed a model combining clinicopathologic and molecular factors. The addition of molecular factors to the model was able to improve the discriminatory ability of the clinicopathologic model alone (P < .001). Finally, they validated these findings in a validation cohort of 146 melanomas. 

“The discriminative ability of the clinicopathologic and molecular model held up when applied to this validation cohort (AUC, 0.93; 95% CI, 0.87–0.97),” they wrote. “Using the suggested cutoff of 10%, the false positive rate was 22% and the false negative rate was 0%.”