TABLE 2.

Advantages and Disadvantages of Molecular Studies for the Diagnosis of Atypical Melanocytic Proliferations

Molecular Tool	Diagnoses Studied In	Advantages	Disadvantages
IHC59,68,69	MIS; actinic keratoses; solar lentigines; and AIMP	Facilitate identification of melanocytes when compared with H&E alone, especially MITF	Melan-A overestimates epidermal melanocytes, suggesting potential overdiagnosis of MIS
		Useful for when tissue is limited	S100 underestimates epidermal melanocytes, suggesting potential underdiagnosis of MIS
CGH70–76	Benign melanocytic nevi and malignant melanoma	Sensitivity and specificity of 80%–90% for diagnosing melanoma	Novel technique with no long-term clinical follow-up
		Detects aberrations of the entire genome in a single assay	Available only at select laboratories
		Some subtypes of melanoma have distinct genomic patterns	Variable insurance coverage
		May increase understanding of the development of melanoma and aid in design of therapeutic strategies	Requires a substantial amount of tissue
		May predict melanoma prognosis	Failure to detect chromosomal abnormalities in a minor subpopulation of tumor cell results in false-negative results
4-probe FISH assay71,77–82,86,107,108	Atypical melanocytic nevi; melanoma; and ambiguous melanocytic proliferations	Sensitivity of 80%–100% and specificity of 95% for diagnosing melanoma	Limited number of probes
		Validated in numerous difficult diagnostic situations	Targets only specific chromosomal aberrations
		May enhance detection of early melanoma when combined with dermatoscopy and histology	Dependent on individual experience
		Increased sensitivity for spitzoid melanomas seen with inclusions of an additional probe	False-positive tests secondary to polyploidy
		Requires less technical expertise than CGH	False-negative tests due to sampling error
		Often covered by insurance	Limited long-term follow-up
			Limited utility for prognostication of melanoma
Gene expression signature87,88	Benign melanocytic nevi and malignant melanoma	Classifies melanocytic lesions as benign or malignant with a sensitivity of 90% and a specificity of 91%	Further validation needed, especially in large cohorts of difficult atypical melanocytic proliferations and melanoma subtypes
		Analysis by qRT-PCR can detect changes in gene expression that may not be an effect of gains or losses of DNA	Currently available studies excluded metastatic lesions, therefore only useful for distinguishing between benign nevi and primary melanomas
			Estimates of sensitivity and specificity may have been biased by use of archived formalin-fixed paraffinembedded tissue sections, which were more likely to be degraded

AIMP, atypical intraepidermal melanocytic proliferation; CGH, comparative genomic hybridization; FISH, fluorescent in situ hybridization; H&E, hematoxylin and eosin; IHC, immunohistochemistry; Melan-A, melanoma antigen recognized by T cells 1; MIS, melanoma in situ; MITF, microphthalmia-associated transcription factor; qRT-PCR, quantitative reverse transcription polymerase chain reaction.