Biopsy Test Predicts Aggressive form of Skin Cancer

The genetic profile of immune cells next to a melanoma could lead to more accurate diagnosis to indicate whether a skin cancer is aggressive enough to metastasize.

The presence of neoplastic cells in sentinel lymph nodes may trigger pathways associated with metastatic progression, and these can be analyzed by transcriptional profiles of archival sentinel node biopsy specimens obtained from melanoma patients.

Scientists at the National Cancer Institute (Milan, Italy) isolated samples taken from 42 melanoma patients and 25 healthy controls, matched for age and sex. Lymph node lymphocytes were obtained from patients recurring or not at the five-year follow-up, whereas blood lymphocytes were obtained from stage IIIC–IV patients and controls.

Gene expression profiles of ribonucleic acid (RNA) microarrays were generated using appropriate technology and a BeadArray Reader (Illumina; San Diego, USA) was used for scanning the arrays. Immunohistochemistry (IHC) staining was performed on consecutive sections on a semiautomated platform by standard diagnostic methods. The fluorescence intensity was measured using a Live/Dead Fixable Dead Cell Stain Kit (Invitrogen; Carlsbad, CA, USA) by a Gallios flow cytometer (Beckman Coulter; Brea, CA, USA).

Among genes upregulated in patients with progressing disease, the tumor necrosis factor (TNF) receptor family member Tumor Necrosis Factor Receptor Superfamily, Member 8 (CD30/TNFRSF8) was confirmed in biopsy specimens from an independent group of patients. Immunohistochemical analysis revealed higher numbers of CD30+ lymphocytes in nodes from progressing patients compared with non-progressing patients. Phenotypic profiling demonstrated that CD30+ lymphocytes comprised a broad population of suppressive or exhausted immune cells.

The authors concluded that transcriptional profiles of formalin-fixed paraffin-embedded sentinel lymph nodes biopsies (SNBs) are a potential informative tool in the clinical setting, for personalized patient treatment. In addition, the strong correlation that they observed between the presence of exhausted/regulatory CD30+ T-cells in SNBs and disease progression suggests a potential role for this marker in the prognostic evaluation and therapeutic targeting of melanoma.

Monica Rodolfo, PhD, an immunotherapy scientist and lead author of the study said, “Using the study of genetic profiles, we found that the sentinel node contains information useful to foresee whether or not a patient with melanoma will have an aggressive cancer. Although this study has a relatively small number of patients, it provides proof-of-principle that the immune system is crucially involved in controlling tumor growth, and that sentinel nodes are endowed with precise information on cancer behavior." The study was published on January 1, 2014, in the journal Cancer Research.

Related Links:
Italian National Cancer Institute
Illumina
Invitrogen