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. 2011 Sep 27;105(7):1023-9.
doi: 10.1038/bjc.2011.288. Epub 2011 Aug 23.

miR-21 and miR-155 are associated with mitotic activity and lesion depth of borderline melanocytic lesions

V Grignol  1 , E T Fairchild, J M Zimmerer, G B Lesinski, M J Walker, C M Magro, J E Kacher, V I Karpa, J Clark, G Nuovo, A Lehman, S Volinia, D M Agnese, C M Croce, W E Carson 3rd
Affiliations

miR-21 and miR-155 are associated with mitotic activity and lesion depth of borderline melanocytic lesions

V Grignol et al. Br J Cancer. .

Abstract

Background: Expression of microRNAs (miRs) has been shown to be altered in many solid tumours and is being explored in melanoma. The malignant potential of some melanocytic lesions is difficult to predict. We hypothesised that characterisation of miR expression in borderline melanocytic proliferations would lead to the identification of a molecular profile that could be used with known prognostic factors to differentiate lesions with high malignant potential.

Methods: The miR expression profile of melanocytic lesions (benign naevi, malignant melanoma and borderline melanocytic tumours) was evaluated by real-time PCR.

Results: PCR analysis revealed primary cutaneous melanomas had an 8.6-fold overexpression of miR-21 and a 7.5-fold overexpression of miR-155 compared with benign naevi (P<0.0001). In situ hybridisation confirmed these results. miR-21 and miR-155 were significantly overexpressed within borderline lesions (P=0.0011 and P=0.0048, respectively). When borderline lesions were categorised by mitotic activity and Breslow thickness, miR-21 was associated with mitotic activity and miR-155 was associated with thickness (P<0.025). Among 14 patients with borderline lesions who underwent sentinel lymph node biopsy (SLNB), positive SLNB was associated with increased miR-21 and miR-155 in the primary lesion compared with lesions with a negative SLNB.

Conclusion: MicroRNA expression profiles can be used to characterise atypical melanocytic lesions.

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Figures

Figure 1
Figure 1
Real-time PCR was used to determine the expression of (A) miR-21, (B) miR-155 and (C) miR-211 in benign naevi (n=22) and malignant melanoma (n=28) tissue samples. miR-21 and miR-155 were significantly upregulated (P<0.0001) and miR-211 was downregulated (P=0.5474). Data were expressed as fold change relative to RNU6B.
Figure 2
Figure 2
In situ hybridisation for miR-21 and miR-155 in (A and B) normal skin (200 × ), (C and D) benign naevi (400 × ) and (E and F) malignant melanoma (400 × ). Specific staining for miR of interest is blue (arrow) and counterstain is pink, some samples contain melanin pigment (brown coloration). Validation of miR-21 and miR-155 expression as determined by real-time PCR is indicated in the corner of each panel. Data shown are representative of n=4 samples for each tissue type.
Figure 3
Figure 3
Real-time PCR was used to determine the expression of (A) miR-21 and (B) miR-155 in several types of borderline melanocytic lesions. Data were expressed as fold change relative to RNU6B. When miR-21 and miR-155 expression levels within individual lesions were plotted against each other a significant positive correlation between the expression of miR-21 and the expression of miR-155 was observed in borderline melanocytic lesions (P<0.001, r=0.77 (C).
Figure 4
Figure 4
Melanocytic lesions with a mitotic activity >1 in 10 HPF (n=19) had significantly higher levels of (A) miR-21 expression levels (P=0.0227) as compared with lesions with no mitotic activity (n=15). Melanocytic lesions with a depth ⩾1 mm (n=17) had significantly greater expression of (B) miR-155 (P=0.0068) as compared with lesions with a depth <1 mm (n=17). Data were expressed as fold change relative to RNU6B.
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