Loss of heterozygosity at 12p13 and loss of p27KIP1 protein expression contribute to melanoma progression.
Little is known about the mechanisms causing p27KIP1 decrease in melanomas. Therefore, we performed loss of heterozygosity (LOH) analysis with polymerase chain reaction at seven different loci surrounding the p27KIP1/CDKN1B gene at 12p13 and direct DNA sequencing analysis of all exons. Furthermore, the immunohistochemical expression of p27KIP1 and Ki-67 was investigated. Only two mutations in the sequence of p27KIP1/CDKN1B were detected, but the number of tumours showing LOH at 12p13 increased significantly with the parameters of tumour progression (pT level, P=0.018; Breslow index, P=0.01; Clark level, P<0.001), with a more aggressive tumour growth (radial versus vertical growth, P=0.018) and tumour subtype (superficial spreading melanomas versus nodular melanomas versus metastases, P<0.001). p27KIP1 protein expression decreased with the Clark level ( P=0.026) and the pT level ( P=0.045). No correlation between LOH affecting 12p13 and p27KIP1 protein decrease in melanomas was stated. This does not exclude the participation of p27KIP1/CDKN1B in p27KIP1 protein decrease, since protein expression is regulated at various cellular levels; but it could also suggest that other tumour suppressors are situated in the same region as p27KIP1/CDKN1B. Taken together, our data shows that loss of p27KIP1 protein expression and LOH at 12p13 contribute to tumour progression in melanoma.
Woenckhaus
Christian
C
Institute of Pathology, University of Greifswald, Fr. Loeffler Strasse 23e, 17489 Greifswald, Germany. woenck@uni-greifswald.de
Fenic
Irina
I
Giebel
Jürgen
J
Hauser
Sebastian
S
Failing
Klaus
K
Woenckhaus
Joachim
J
Dittberner
Thomas
T
Poetsch
Micaela
M
D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D002881:Chromosomes, Human, Pair 12; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D019656:Loss of Heterozygosity; D008545:Melanoma / Q000737:chemistry / Q000235:genetics*; D018895:Microsatellite Repeats
C436291:CDKN1B protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27