P16INK4a as a progression/regression tumour marker in LSIL cervix lesions: our clinical experience.

PURPOSE OF INVESTIGATION: The aim of this prospective study was the evaluation of low-grade intraepithelial lesion (LSIL) lesions evolvement in woman with evidence of high risk HPV infection and p 16 4a negative expression. MATERIALS AND METHODS: 150 women with cytological diagnosis of LSIL were selected to be underwent to three years of follow-up consisting in smear test, colposcopy, and protein p16I4a investigation every six months and HPV-test every 12 months. RESULT: Final follow-up showed 45 cases of spontaneous lesion regression and 42 cases of persistence with absence of protein p164NK4a in all of them. There were three cases of disease progression to CIN2, two at 18-month follow-up and one at last follow-up. Disease progression was characterized of p16NK4a expression. CONCLUSION: p16l4a should help to identify which LSIL cases are inclined to the progression of the disease and focalize which patients are eligible for specific treatment.

Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions.

Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated PrP27 - 30 detectable by the 3F4 antibody against human PrP109 - 112. We recently identified a new PK-resistant PrP species, designated PrP*20, in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 - 108 but not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic mutant PrP accumulate not only PrP*20 but also a small amount of 3F4-detected PK-resistant PrP27 - 30. Remarkably, during the course of human prion disease, a transition from an increase in 1E4-detected PrP*20 to the occurrence of the 3F4-detected PrP27 - 30 was observed. Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases.