Decreased immunoreactivity for cell-cycle regulator p27(Kip1) in Kaposi's sarcoma correlates with higher stage and extracutaneous involvement.
A consistent relationship has been established between the development of Kaposi's sarcoma (KS) and human herpes virus-8 (HHV8) infection. HHV8-encoded v-cyclin, through its complexing with cyclin-dependent kinase 6, contributes to the phosphorylation and proteasome-mediated degradation of p27(Kip1). On the other hand, down-regulation of p27(Kip1) expression seems to facilitate metastatic dissemination in a variety of human neoplasms. Although the neoplastic nature of KS remains controversial, it has been repeatedly demonstrated that in some patients KS may behave as a malignant neoplasm and follow an ominous course, especially in HIV-positive patients and when associated with extracutaneous involvement. To determine whether decreased p27(Kip1) levels are also related to more aggressive behaviour in KS, it was decided to investigate p27(Kip1) immunoreactivity in KS biopsy specimens and its possible changes in relation to cutaneous versus extracutaneous involvement and HIV serological status. Forty-nine cases of KS (29 AIDS-related and 21 classical) corresponding to 30 cutaneous biopsy specimens (ten macules, seven plaques, and 13 tumours) and 19 extracutaneous biopsy specimens were immunostained to determine the expression of p27(Kip1) and the proliferation marker Ki-67 antigen. The mean percentages of p27(Kip1)-positive cells were significantly higher in biopsy specimens from skin lesions (77.8+/-21.1) than in those from extracutaneous locations (42.0+/-26.0). Amongst cutaneous lesions, p27(Kip1) expression was significantly higher in macules (83.8+/-18.5) and plaques (91.4+/-6.4) than in tumours (65.8+/-22.6). Ki-67 immunoreactivity showed no correlation with any of the variables studied. These results lend support to the hypothesis that decreased levels of p27(Kip1), which may have been brought about by HHV8 infection, play a role in KS progression through its various histopathological stages, to its eventual extracutaneous spread.
Fernández-Figueras
M T
MT
Department of Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Puig
L
L
Penín
R M
RM
Mate
J L
JL
Bigatà
X
X
Ariza
A
A
D002452:Cell Count; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D016370:Gene Products, rex; D015658:HIV Infections / Q000150:complications / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000276:immunology; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000235:genetics* / Q000473:pathology
D016370:Gene Products, rex; D019394:Ki-67 Antigen