CHICAGO – Investigators have identified four genes that are overexpressed in primary melanoma, including one, CXCL1, that holds promise as a strong predictor of future metastatic disease, according to study results presented at the Society of Surgical Oncology Annual Cancer Symposium.
The study implicated four genes strongly expressed in primary melanoma tumors of patients who develop distant metastases – CXCL1, CXCL2, CBL, and CD276 – said Jennifer Erdrich, MD, MPH, of Cedars Sinai Medical Center, Los Angeles. However, CXCL1 stood out. “CXCL1 overexpression is an independent predictor of developing metastatic disease. Patients with CXCL1 overexpression in the primary tumor in our study had decreased overall 5-year survival.” CXCL1 may be a useful predictive marker in primary melanoma and a potential target for immunotherapy, she said.
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The rationale for analyzing the 79 genes implicated in cancer only rather than the entire array of 22,000 genes was to reduce the odds of a high false-discovery rate from 5% to 0.007%. “This is what strengthens our findings in a cohort of 37 patients,” Dr. Erdrich said.
The study analyzed pathological characteristics of the metastatic and nonmetastatic groups. Most characteristics were similar between the two groups, including location of the primary tumor in the trunk and extremities of 67% and 71%, respectively, and age of 60 years and older. The analysis noted two deviations: primary tumor size was thicker in the metastatic group (2.1 mm vs. 1.05 mm; P = .6), although Dr. Erdrich noted this was “not significantly different”; and a higher rate of ulceration in the metastatic group (50% vs. 13%; P = .05).
The genes CXCL1 and CXCL2 are both chemokines involved in growth and inflammation. “CXCL1 expression was 2.51 times greater in the metastatic group,” Dr. Erdrich said (P less than .001). Overexpression in the other three genes of interest was: CXCL2, 1.68 times greater (P less than .01); CD276, which is involved in T-cell immunity, 1.16 times greater (P = .04); and C-CBL, which is a photo-oncogene involved in the ubiquitin pathway, 1.15 times greater (P = .01). “The overexpression of all four of these was statistically significant,” she said.
Univariate analysis found ulceration of the primary along with overexpression of