The chemoresistance gene ABCG2 (MXR/BCRP1/ABCP1) is not expressed in melanomas but in single neuroendocrine carcinomas of the skin.
BACKGROUND
As the molecular mechanisms in melanoma chemoresistance remain unknown to date, we hypothesized these tumors to express the ATP-binding cassette (ABC) transporter G2 (ABCG2/MXR/BCRP1/ABCP1), a recently detected membrane transporter and putative stem-cell marker. Besides melanoma, we addressed the neuroendocrine carcinoma of the skin (Merkel cell carcinoma), another cutaneous cancer supposed to originate from neuroectoderm and usually chemoresistant.


RESULTS
Upon semiquantitative reverse transcription polymerase chain reaction, ABCG2 mRNA expression was not upregulated in 18 melanoma resection specimens when compared with 19 acquired melanocytic nevi from which melanomas are known to often arise (Mantel-Haenszel test, p=0.3). At protein level, immunohistochemistry was negative in all 66 investigated melanoma resection specimens (50 primary melanomas and 16 cutaneous/subcutaneous metastases) and in 19 acquired melanocytic nevi. Among 29 neuroendocrine carcinomas of the skin, ABCG2 protein was detected in single clusters of cells in three tumors. As a positive control, three dermatofibrosarcomas were also stained and showed ABCG2 protein expression of the endothelial cells of the blood vessels.


CONCLUSIONS
Altogether, chemoresistance of melanomas and neuroendocrine carcinomas of the skin cannot be explained by expression of the ABCG2-chemoresistance gene. Most of these tumors do not exhibit this potential stem-cell feature.
Deichmann
Martin
M
Department of Dermatology, Heidelberg University Clinics, Heidelberg, Germany. martin_deichmann@web.de
Thome
Marianne
M
Egner
Ursula
U
Hartschuh
Wolfgang
W
Kurzen
Hjalmar
H
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D015266:Carcinoma, Merkel Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009508:Nevus, Pigmented / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm