A small multimarker panel using simple immunohistochemistry methods is an adjunct to stage for cutaneous melanoma prognosis

Abstract

Melanoma is an aggressive cancer. Outcomes can vary significantly for lesions within the same pathological stage - a problem of increasing relevance with the promise of adjuvant treatments on the basis of immune checkpoint modulators and targeted therapies. The use of a panel of prognostic molecular biomarkers as an adjunct to stage represents a possible solution. Immunohistochemistry-based biomarkers offer greater potential for translation into clinical practice than biomarkers utilizing more complex methods. Many immunohistochemistry-based biomarkers have been identified through discovery studies, but rigorous validation of these is scarce. We take the first steps towards validating a combination of three such biomarkers in a prognostic panel - 5hmC, ki-67 and p16. Immunohistochemistry was performed on a cohort of 50 melanomas to determine the expression of 5hmC, ki-67 and p16. 5hmC and p16 showed statistically significant differences in metastasis-free survival between low-score and high-score groups, whereas the use of all three biomarkers together with stage could predict the 5-year metastasis risk more accurately than stage alone. Our results suggest that the use of multimarker panels to improve the accuracy of prognostic predictions is feasible and worthy of further study. We have shown that a small immunohistochemistry-based panel utilizing simple, inexpensive, reproducible methods can be an effective adjunct to stage in prognostic prediction. A follow-up study consisting of a large cohort of melanomas is now indicated to continue the development of the prognostic panel.

Biglycan expression in the melanoma microenvironment promotes invasiveness via increased tissue stiffness inducing integrin-β1 expression

“…of Dermatology, University Hospital Freiburg, Germany, from whom a biopsy was available, were analyzed. Patients were divided according to their prognosis into the group with a poor prognosis (melanoma-related death within the period), versus the group with a good prognosis (alive within the period), according to previous stratification approaches [37, 38]. More detailed patient characteristics are listed in Supplementary Table 1.…”

Identification of risk in cutaneous melanoma patients: Prognostic and predictive markers

“…Although protein expression significantly correlated with recurrence and survival and all high‐risk patients had events within 5 years, the E1690 cohort was primarily composed of high‐risk tumors with five‐year survival rates that approached 50% among low‐risk patients. Similar to other panels that have been reported, the clinical validity and utility of the multiprotein marker in an early stage melanoma population remains to be determined …”

Biomarkers in Malignant Melanoma: Recent Trends and Critical Perspective

“…In contrast, a cluster of biomarkers for one disease would be a better diagnostic tool with much higher sensitivity, specificity, and clinical accuracy. Therefore, new investigations called "proteomic profiling" or "multimarker profiling" focus on the identification of multiple co-expressed biomarkers or signature biomarker patterns which allow early detection, staging, therapeutic monitoring, and prognostic predictions (7,(84)(85)(86)(87)(88). This approach can be adopted for both serum and tissue specimens.…”