Expression patterns of hair and epithelial keratins and transcription factors HOXC13, LEF1, and beta-catenin in a malignant pilomatricoma: a histological and immunohistochemical study.
BACKGROUND
We have previously shown that benign pilomatricomas not only maintain the sequential expression of the hair matrix and precortex keratins hHa5 and hHa1 of normal hair follicles in their transitional cell compartment, but also preserve the association of hHa5 expression with that of its regulatory homeoprotein HOXC13 in the lower transitional cell compartment. In contrast, hHa1 expression in the upper transitional cell compartment is uncoupled from the nuclear co-expression of the LEF1/beta-catenin complex seen in normal hair follicles (Cribier et al., J Invest Dermatol 2004; 122: 1078).


METHODS
Formalin-fixed paraffin sections of the tumor were examined using a panel of mono- and polyclonal hair and epithelial keratin antibodies as well as antibodies against HOXC13, LEF1, and beta-catenin.


RESULTS
Morphologically, the malignant pilomatricoma investigated here clearly deviated from the described major tumor type by a large number of differently sized parakeratotic squamoid whorls emerging within the mass of basaloid cells and surrounded by cells remembering transitional cells, but only rarely containing shadow cells and signs of calcification. We show that hHa5/HOXC13 co-expression was maintained in transitional cell areas, in which hHa1 expression was much stronger than in benign pilomatricomas, but again uncoupled from concomitant nuclear LEF1/beta-catenin expression. Surprisingly, however, and in clear contrast to benign pilomatricomas, these transitional cells co-expressed the epithelial keratins K5, K14, and K17, with the latter being as strongly expressed as hHa1, both also staining the entire inner mass of the parakeratotic whorls.


CONCLUSIONS
Although the malignant pilomatricoma investigated here was distinctive in that it contained a multitude of parakeratinizing whorls and no signs of calcification, it shared both hHa5/HOXC13 co-expression and disrupted hHa1/beta-catenin-LEF1 expression in its transitional cell compartment around the whorls with benign pilomatricomas. However, in clear contrast to the latter, transitional cells of the malignant tumor also strongly expressed the epithelial keratins K5, K14, and K17. We speculate that the observed dominance of the epithelial differentiation pathway over the competing conventional shadow cell differentiation pathway may prevent massive calcification of the tumor.
Cribier
Bernard
B
Department of Dermatology, University Hospital, Strasbourg, France.
Worret
Wolf-Ingo
WI
Braun-Falco
Markus
M
Peltre
Bernard
B
Langbein
Lutz
L
Schweizer
Jürgen
J
D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006197:Hair / Q000378:metabolism*; D006201:Hair Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000145:classification / Q000378:metabolism*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D008297:Male; D018296:Pilomatrixoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014157:Transcription Factors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C410305:HOXC13 protein, human; D018398:Homeodomain Proteins; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D014157:Transcription Factors; D051176:beta Catenin; D007633:Keratins