Background: Recent in vitro studies provide evidence that the cell cycle molecules pRb, p53 and MDM2 form a tightly regulated protein network. In this study, we examined the relationship of this protein network in a series of non-small cell lung carcinomas (NSCLCs), with the kinetic parameters, including proliferative activity or proliferation index (PI) and apoptotic index (AI), and ploidy status of the tumors. Material and Methods: A total of 87 NSCLCs were examined using immunohistochemical and molecular methods in order to estimate the status of the pRb-p53-MDM2 network. The kinetic parameters and the ploidy status of the tumors were assessed by in situ assays. The possible associations between alterations of the network, kinetic parameters and ploidy status of the carcinomas were assessed with a series of statistical methods. Results: Aberrant expression of pRb (Ab) and overexpression of p53 (P) and MDM2 (P) proteins were observed in 39%, 57%, and 68% of the carcinomas, respectively. The comprehensive analysis revealed that concurrent alterations in all three cell cycle regulatory molecules were the most frequent pattern, pRb(Ab)/p53(P)/MDM2(P); this "full abnormal" phenotype represented approximately 27% of the cases. This immunoprofile obtained the highest

No abstract

IMPORTANCE Keratinocyte carcinomas (KCs), consisting of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs), are the most common human malignant neoplasms. Several risk factors have been implicated in KC development. For some SCCs, particularly those in immunocompromised patients, human papillomavirus (HPV) may be an important factor. OBJECTIVE To determine whether quadrivalent HPV vaccination would affect the development of KCs in immunocompetent patients with a history of multiple KCs.DESIGN, SETTING, AND PARTICIPANTS Two patients with a history of multiple KCs-a man in his 70s (patient 1) and a woman in her 80s (patient 2)-were treated in a private dermatology practice. Each patient received 3 doses of the quadrivalent HPV vaccine at 0, 2, and 6 months in 2013, and both patients underwent full-body skin examinations at least every 3 months. Biopsy-proven skin cancers were recorded for 16 months (for patient 1) or 13 months (for patient 2) after the first dose of vaccine and then compared with the number of biopsy-proven skin cancers recorded over a similar period before the first dose of vaccine. The period of observation was from October 18, 2011, to June 21, 2014. MAIN OUTCOMES AND MEASURESThe numbers of new SCCs and BCCs after the first dose of the quadrivalent HPV vaccine.RESULTS Patient 1 had a mean of 12 new SCCs and 2.25 new BCCs per year before vaccination. After vaccination, he developed 4.44 SCCs and 0 BCCs per year, a 62.5% reduction in SCCs and a 100% reduction in BCCs. Patient 2 had a mean of 5.5 new SCCs and 0.92 new BCCs per year before vaccination. After vaccination, she developed 1.84 SCCs and 0 BCCs per year, a 66.5% reduction in SCCs and a 100% reduction in BCCs. The quadrivalent HPV vaccine was well tolerated by both patients and had no adverse effects.CONCLUSIONS AND RELEVANCE A reduction of SCCs and BCCs was observed in 2 patients after administration of the quadrivalent HPV vaccine. These findings highlight the possibility that cutaneous SCC development, and perhaps BCC development, may be driven in part by HPV in immunocompetent patients. Human papillomavirus vaccination may represent an efficacious, cost-effective, readily available, and well-tolerated strategy for preventing KCs.

No abstract

No abstract