Taping into Accuracy: RNA Test for Melanoma Diagnosis

Original Article: RNA analysis of tape strips to rule out melanoma in lesions clinically assessed as cutaneous malignant melanoma: A diagnostic study

What are the key takeaways of this article?

The ability to distinguish cutaneous malignant melanoma (CMM) from a benign nevi remains a challenge clinically for both dermatology and generalist practices. It is estimated that the amount of lesions removed to diagnose one CMM in physicians with dermatoscopy experience is eight, and up to 20 for other providers. While surgical removal has been used as a diagnostic tool for CMM, a non-invasive technique has been proposed as an alternative. A non-invasive RNA test, known as a pigmented lesion assay (PLA), utilizes tape from lesional surfaces to investigate over 17 genes in order to distinguish CMM from benign nevi. Previous case controlled studies have tested this technique’s sensitivity and specificity but raised concern for misdiagnosis. As such, the goal of this article was to study the utility of PLA with a further developed technique for further validity.

The authors examined 11 genes in 200 lesions from patients 18 and older. Patients were recruited through referrals from primary care to dermatology or plastic surgery in Copenhagen University Hospital. All participants were blinded. Inclusion criteria was suspected CMM for removal, and exclusion criteria included ulceration, bleeding, diameter shorter than 3mm, recent treatment with steroids, serous exudation, pregnant, or breastfeeding. Suspected lesions were tape striped twice then sent for surgical excision. The tape underwent quantitative real-time polymerase chain reaction to measure the expression level of each gene. The test is based on the relation of two oncogenes, KIT and PRAME, to a housekeeping gene RPL18. Of note, overexpression of PRAME is seen in Basal Cell Carcinoma, Squamous Cell Carcinoma and Melanomas.

Of the 200 lesions, histopathological analysis from excisions showed 73 CMMs and 127 non-CMM lesions. Of those 73 CMMs, 57 were superficial spreading melanoma, 12 were superficial spreading melanomas in situ, one was lentigo maligna melanoma in situ, and 2 were nodular melanomas. Overall, the majority of lesions were in situ and notably, the majority were below 1mm thickness. The tape test yielded the same results and was positive for all lesions that were histopathologically diagnosed as CMMs. The tape also yielded a positive result for 86 other lesions. The skin lesions were identified as follows: 42 compound nevi, 12 seborrheic keratoses, 10 junctional nevi, 7 intradermal nevi, 5 BCCs, 3 hemangiomas, 2 Spitz nevi, 1 actinic keratosis, 1 solar lentigo, 1 dermatofibroma, 1 instance of inflammation, and 1 trichoepithelioma. For these lesions, the test could not rule out CMMs and histopathological investigation was necessary. Finally, a total of 41 lesions were negative with the tape test and CMM could be ruled out. Tape levels were quantified as cycle threshold values (Ct); the lower the Ct, the higher the RNA. There was significant negative correlation between Ct value and lesional surface area; the larger the lesions, the more RNA was detected. Interestingly, there was a negative correlation between age and Ct value, as well as storage time and Ct values. The authors found that with longer storage time there was increased breakdown of RNA.

In summary, this study aimed to investigate the utility of RNA tape test as a rule out method for CMMs. The authors concluded a specificity of 100% and sensitivity of 32%. These results indicate that the tape test is a successful method to decrease the unnecessary removal of benign lesions without missing CMMs. Thus, RNA analysis from tape strips can be used as a diagnostic tool for differentiating between cutaneous malignant melanoma and benign lesions prior to undergoing surgical excision, thereby reducing unnecessary excisions.

Publication Date: October 21st, 2023

Reference: Heerfordt IM, Philipsen PA, Andersen JD, Langhans L, Schmidt G, Morling N, Wulf HC. RNA analysis of tape strips to rule out melanoma in lesions clinically assessed as cutaneous malignant melanoma: A diagnostic study. Journal of the American Academy of Dermatology. 2023 May 22.

Summary By: McKenzie Van Eaton