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Comparative Study
. 2004 Oct;165(4):1395-400.
doi: 10.1016/S0002-9440(10)63397-4.

Molecular genetic evidence for different clonal origins of epithelial and stromal components of phyllodes tumor of the prostate

Affiliations
Comparative Study

Molecular genetic evidence for different clonal origins of epithelial and stromal components of phyllodes tumor of the prostate

Ryan P McCarthy et al. Am J Pathol. 2004 Oct.

Abstract

Phyllodes tumor of the prostate is a rare neoplasm, composed of epithelium-lined cysts and channels embedded in a variably cellular stroma. The pathogenetic relationship of the epithelium and stroma is unknown and whether each is a clonal neoplastic element is uncertain. We studied the clonality of phyllodes tumors from six patients who underwent either enucleation or transurethral resection as their initial treatment. This was followed by total prostatectomy in three of the patients. Laser-assisted microdissection was performed to extract epithelial and stromal components of phyllodes tumor from formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 7q31 (D7S522), 8p21.3-q11.1 (D8S133, D8S137), 8p22 (D8S261), 10q23 (D10S168, D10S571), 17p13 (TP53), 16q23.2 (D16S507), 12q11-12 (D12S264), 17q (D17S855), 18p11.22-p11 (D18S53), and 22q11.2 (D22S264). In each tumor, stroma and epithelium were analyzed separately. Gel electrophoresis with autoradiography was used to detect loss of heterozygosity. All tumors showed allelic loss in one or more loci of both the epithelial and stromal components. The frequency of allelic loss in the epithelial component was 2 of 5 (40%) at D7S522, 2 of 6 (33%) at D8S133, 1 of 5 (20%) at D8S137, 3 of 6 (50%) at D8S261, 4 of 4 (100%) at D10S168, 4 of 6 (67%) at TP53, 2 of 6 (33%) at D10S571, 6 of 6 (100%) at D16S507, 1 of 5 (20%) at D12S264, 1 of 6 (17%) at D17S855, 2 of 6 (33%) at D18S53, and 2 of 5 (40%) at D22S264. The frequency of allelic loss in the stromal component was 2 of 5 (40%) at D7S522, 1 of 6 (17%) at D8S133, 2 of 5 (40%) at D8S137, 3 of 6 (50%) at D8S261, 1 of 4 (25%) at D10S168, 3 of 6 (50%) at TP53, 2 of 6 (33%) at D10S571, 3 of 6 (50%) at D16S507, 1 of 5 (20%) at D12S264, 0 of 6 (0%) at D17S855, 1 of 6 (17%) at D18S53, and 0 of 5 (0%) at D22S264. The pattern of allelic loss is significantly different in both stroma and epithelium statistically; completely concordant allelic loss patterns were not seen in any tumor examined. Our data demonstrate that both epithelial and stromal components of phyllodes tumor of the prostate are clonal, supporting the hypothesis that both elements are neoplastic. While both epithelium and stroma are clonal proliferations, they appear to have different clonal origins.

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Figures

Figure 1-4246
Figure 1-4246
Laser microdissection of a phyllodes tumor of prostate (Case 3). It illustrated epithelial (*) and stromal (♦) components of tumor before microdissection (A) and after microdissection (B).
Figure 2-4246
Figure 2-4246
Comparison of frequency of allelic loss between epithelial and stromal components of phyllodes tumor.
Figure 3-4246
Figure 3-4246
Representative results of loss of heterozygosity analysis (Case 3). DNA was prepared from normal tissue (N), epithelial (E), and stromal cells (S) of the phyllodes tumor, amplified by polymerase chain reaction using polymorphic markers D7S522, D8S133, D8S137, D8S261, D10S168, D10S571, D12S264, D16S507, TP53, D17S855 D18S53, D22S264, and separated by gel electrophoresis. Arrows, allelic bands.
Figure 4-4246
Figure 4-4246
Different parts of the same component (epithelial or stromal) showed the same LOH pattern. DNA was prepared from normal tissue (N), epithelial (E), and stromal cells (S) of the phyllodes tumor and amplified by polymerase chain reaction. E1 and E2 represent epithelial components sampled from different tumor parts; S1 and S2 represent stromal components sampled from different tumor parts. The same LOH pattern was seen in tumor components of left and right sides of a radical prostatectomy specimen (Case 6) and multiple areas of different case (Case 2). Arrows, allelic bands.

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