title: Expression of p53 and TP53 mutational analysis in malignant neoplasms arising in preexisting spiradenoma, cylindroma, and spiradenocylindroma, sporadic or associated with Brooke-Spiegler syndrome.
abstract: We performed immunohistochemical assessment of p53 expression and TP53 mutational analysis of 15 malignant neoplasms arising from preexisting benign cylindroma, spiradenoma, and spiradenocylindroma, sporadic or associated with Brooke-Spiegler syndrome. At least weak and focal p53 positivity was present in 13 of the 15 lesions. Successful PCR and sequencing were possible in 12 of the 15 cases. In one case only there were 2 p53 mutations, one being a c.673-1G>A splice-site mutation in the 3'-end of intron 6 (position--g.15289G>A, contig gb.AY838696.1) and the second being a c.743G>A (p.R248Q) mutation in exon 7 (position--15360G>A, contig gb.AY838696.1). Single nucleotide polymorphisms were detected in all 12 malignant cases analyzed. As a control group, we included 12 randomly selected sporadic cases of spiradenoma (n = 5), cylindroma (n = 4), and spiradenocylindroma (n = 3). None of the 12 benign control group cases harbored a TP53 mutation, whereas all 12 demonstrated single nucleotide polymorphisms identical to those detected in the malignant tumor group. Immunohistochemically, 1 cylindroma and 2 spiradenomas demonstrated weak and focal p53 positivity. In conclusion, we found a fairly high rate of p53 expression in malignant neoplasms arising from preexisting benign spiradenomas, cylindromas, and spiradenocylindromas. However, the mutation rate of TP53 was low. Whereas immunostaining for p53 has been suggested as an adjunct tool to differentiate benign spiradenoma, cylindroma, and spiradenocylindroma from their malignant counterparts, its utility is limited by its heterogeneous pattern of expression, especially the sometimes lack of staining in clearly malignant areas and the occurrence of focal, weak positivity in the benign residua or in unequivocally benign neoplasms.
authors.affiliation: From the *Sikl's Department of Pathology, Charles University Medical Faculty Hospital, Pilsen, Czech Republic; †Division of Tissue Pathology, PathWest Laboratory Medicine WA, Nedlands, WA, Australia; ‡Department of Pathology, Academy of Postgraduate Studies, Minsk, Belorussia; §Clinical Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria; ¶Department of Dermatopathology, St. John's Institute of Dermatology, St. Thomas's Hospital, London, England, UK; and ‖Bioptical Laboratory, Pilsen, Czech Republic.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Kazakov
authors.forename: Petr
authors.initials: P
authors.lastname: Grossmann
authors.forename: Dominic V
authors.initials: DV
authors.lastname: Spagnolo
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanecek
authors.forename: Marina
authors.initials: M
authors.lastname: Vazmitel
authors.forename: Denisa
authors.initials: D
authors.lastname: Kacerovska
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zelger
authors.forename: Eduardo
authors.initials: E
authors.lastname: Calonje
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D013544:Sweat Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D013577:Syndrome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53