Allelic deletion at 9p21-22 in primary cutaneous CD30(+) large cell lymphoma.
The genetic alterations responsible for the development of cutaneous lymphoma are largely unknown. Chromosome region 9p21 contains a gene locus encoding an inhibitor of cyclin-dependent kinase 4, and heterozygous deletions of this tumor suppressor gene (p16) have been shown in a variety of malignant tumors. We studied 11 randomly selected cutaneous CD30-positive large cell lymphomas. Several areas containing 20-50 CD30-positive lymphocytes were microdissected in each case and subjected to single-step DNA extraction. Loss of heterozygosity analysis was performed using polymorphic markers at 9p21 (IFNA, D9S171, D9S169) and 17p13 (TP53). Samples from normal cells apart from CD30-positive lymphocytes, e.g., CD30-negative lymphohistiocytic infiltrates and normal epidermal layer, were also obtained in all cases from the same slide for comparison with the tumor samples. Expression of CD30 and T-lineage antigens (CD3, CD45Ro) was confirmed in all cases. Immunohistochemical staining for p16 and p53 was performed using the monoclonal antibodies sc-1661 and DO-7, respectively. Of the 11 informative cases, seven (64%) exhibited loss of heterozygosity at least for one marker at 9p21 (p16), whereas no allelic deletions were found for the polymorphic marker at 17p13 (p53). On immunohistochemistry loss of the p16 protein was detected in two of 11 cases. Nuclear staining for p53 protein was found in four of 11 cases. Here, we provide the first evidence of the involvement of the tumor suppressor gene p16 in primary cutaneous large cell lymphoma. Whether p16 deletion in these lymphomas is associated with disease progression and whether this method could serve as an early marker to detect lymphomas at an early stage needs to be addressed in future studies. J Invest Dermatol 115:1104-1107 2000
Böni
R
R
Department of Dermatology, University Hospital, Zürich, Switzerland. rboeni@derm.unizh.ch
Xin
H
H
Kamarashev
J
J
Utzinger
E
E
Dummer
R
R
Kempf
W
W
Kutzner
H
H
Burg
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics*; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000235:genetics*