title: Loss of heterozygosity at 12p13 and loss of p27KIP1 protein expression contribute to melanoma progression.
abstract: 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.
authors.affiliation: Institute of Pathology, University of Greifswald, Fr. Loeffler Strasse 23e, 17489 Greifswald, Germany. woenck@uni-greifswald.de
authors.forename: Christian
authors.initials: C
authors.lastname: Woenckhaus
authors.forename: Irina
authors.initials: I
authors.lastname: Fenic
authors.forename: Jürgen
authors.initials: J
authors.lastname: Giebel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hauser
authors.forename: Klaus
authors.initials: K
authors.lastname: Failing
authors.forename: Joachim
authors.initials: J
authors.lastname: Woenckhaus
authors.forename: Thomas
authors.initials: T
authors.lastname: Dittberner
authors.forename: Micaela
authors.initials: M
authors.lastname: Poetsch
mesh_terms: 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
chemical_list: C436291:CDKN1B protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27