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.