The loss of cell cycle control is a critical step in the development of neopla sia. The p16 protein has been identified as a tumor suppressor protein, which bi nds specifically to the cyclin-de-pendent kinase CDK-4, i...The loss of cell cycle control is a critical step in the development of neopla sia. The p16 protein has been identified as a tumor suppressor protein, which bi nds specifically to the cyclin-de-pendent kinase CDK-4, inhibiting the cataly tic activity of the CDK4-cyclin D complex, and thereby acts as a negative cell cycle regulator. In the present study, we compared the expression of p16 protein in cases with leiomyoma, uterine smooth muscle tumor of uncertain malignant pot ential (STUMP), and leiomyosarcoma (LMS). P16 expression was investigated by imm unohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS. P16 was expressed in 12 %of leiomyomas, in 21%of STUMP, and in 57%of LMS. A statistically significant difference regarding the frequency of p16 protein expression was observed betwe en LMS and STUMP (P < 0.05) as well as between LMS and leiomyoma (P < 0.05), but not between STUMP and leiomyoma (P >0.05). Likewise, the staining intensity did significantly differ between LMS and leiomyoma and between LMS and STUMP (P < 0 .05), but no statistical significant difference was observed between STUMP and l eiomyoma (P >0.05). No statistically significant correlation between p16 express ion and clinical stage, age, vascular space involvement, and recurrence disease could be found in patients with LMS (P >0.05). Additionally, the overall surviva l did not significantly differ between p16-positive and p16-neg-ative cases ( P >0.05). We found that p16 was more frequently and more strongly expressed in L MS compared to STUMP and leiomyoma. We therefore concluded that p16 might play a n important role in sarcomagenesis. Furthermore, p16 might be a useful immunohistochemical mark er, which could help to distinguish cases of smooth muscle tumors in which histo logic features are ambiguous or borderline, but the use of p16 in a diagnostic s etting should await further clinical studies and clarification of the mechanisms .展开更多
Background: Imiquimod is a modifier of the immune response that has been prov en to be an effective treatment for basal cell carcinoma (BCC). However, its mec hanism of action is still unknown. Objectives: To determin...Background: Imiquimod is a modifier of the immune response that has been prov en to be an effective treatment for basal cell carcinoma (BCC). However, its mec hanism of action is still unknown. Objectives: To determine whether imiquimod modifies the expression of proteins such as Bcl- 2, Ki67, p53 and the BCC apoptotic inde x. Patients and methods: Thirty Caucasian patients with primary BCCs larger than 8 mm in diameter were included in a double-blind randomized clinical and immu nohistochemical study which was designed in a reference university hospital. The 30 BCCs were randomized in two treatment arms between September 2001 and Februa ry 2002. Twenty-four BCCs were treated with imiquimod 5% cream and six BCCs w ith Aldara. (3M Pharmaceuticals) excipient. Histological samples were obtained b efore treatment and on days 8 and 15 during the course of treatment. The BCC exp ression of Bcl-2, Ki67 and p53 was determined in paraffin samples and the apop totic index of the BCC was studied using the TUNEL technique (terminal deoxynucl eotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labelli ng) in frozen samples. All variables were evaluated quantitatively in fields wit h a magnification× 400. Results: The BCCs treated with imiquimod showed a decre ase in the expression of Bcl-2 (88- 7% before treatment, 61.4% day 15, P = 0.01) and an increase in the apoptotic index (0.53% before treatment, 1.66% day 15, P = 0- 002), which were not observed in the BCCs treated with the exc ipient. Ki67 and p53 did not show significant changes in any group. Conclusions: Imiquimod reduces the expression of Bcl- 2 in the BCC cells and increases the BCC apoptotic index.展开更多
文摘The loss of cell cycle control is a critical step in the development of neopla sia. The p16 protein has been identified as a tumor suppressor protein, which bi nds specifically to the cyclin-de-pendent kinase CDK-4, inhibiting the cataly tic activity of the CDK4-cyclin D complex, and thereby acts as a negative cell cycle regulator. In the present study, we compared the expression of p16 protein in cases with leiomyoma, uterine smooth muscle tumor of uncertain malignant pot ential (STUMP), and leiomyosarcoma (LMS). P16 expression was investigated by imm unohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS. P16 was expressed in 12 %of leiomyomas, in 21%of STUMP, and in 57%of LMS. A statistically significant difference regarding the frequency of p16 protein expression was observed betwe en LMS and STUMP (P < 0.05) as well as between LMS and leiomyoma (P < 0.05), but not between STUMP and leiomyoma (P >0.05). Likewise, the staining intensity did significantly differ between LMS and leiomyoma and between LMS and STUMP (P < 0 .05), but no statistical significant difference was observed between STUMP and l eiomyoma (P >0.05). No statistically significant correlation between p16 express ion and clinical stage, age, vascular space involvement, and recurrence disease could be found in patients with LMS (P >0.05). Additionally, the overall surviva l did not significantly differ between p16-positive and p16-neg-ative cases ( P >0.05). We found that p16 was more frequently and more strongly expressed in L MS compared to STUMP and leiomyoma. We therefore concluded that p16 might play a n important role in sarcomagenesis. Furthermore, p16 might be a useful immunohistochemical mark er, which could help to distinguish cases of smooth muscle tumors in which histo logic features are ambiguous or borderline, but the use of p16 in a diagnostic s etting should await further clinical studies and clarification of the mechanisms .
文摘Background: Imiquimod is a modifier of the immune response that has been prov en to be an effective treatment for basal cell carcinoma (BCC). However, its mec hanism of action is still unknown. Objectives: To determine whether imiquimod modifies the expression of proteins such as Bcl- 2, Ki67, p53 and the BCC apoptotic inde x. Patients and methods: Thirty Caucasian patients with primary BCCs larger than 8 mm in diameter were included in a double-blind randomized clinical and immu nohistochemical study which was designed in a reference university hospital. The 30 BCCs were randomized in two treatment arms between September 2001 and Februa ry 2002. Twenty-four BCCs were treated with imiquimod 5% cream and six BCCs w ith Aldara. (3M Pharmaceuticals) excipient. Histological samples were obtained b efore treatment and on days 8 and 15 during the course of treatment. The BCC exp ression of Bcl-2, Ki67 and p53 was determined in paraffin samples and the apop totic index of the BCC was studied using the TUNEL technique (terminal deoxynucl eotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labelli ng) in frozen samples. All variables were evaluated quantitatively in fields wit h a magnification× 400. Results: The BCCs treated with imiquimod showed a decre ase in the expression of Bcl-2 (88- 7% before treatment, 61.4% day 15, P = 0.01) and an increase in the apoptotic index (0.53% before treatment, 1.66% day 15, P = 0- 002), which were not observed in the BCCs treated with the exc ipient. Ki67 and p53 did not show significant changes in any group. Conclusions: Imiquimod reduces the expression of Bcl- 2 in the BCC cells and increases the BCC apoptotic index.
