Overexpression of p16(INK4a) in Mastocytosis (Urticarial Pigmentosa).

The expression of p16(INK4a) has been reported to induce cell-cycle arrest and cellular senescence. The p16(INK4a) expression has never been examined in human mast cells and mastocytosis. We immunohistologically examined the expression of p16(INK4a) and tryptase in 5 normal human skin and 4 mastocytosis. In normal mast cells, only 5.9 ± 3.4 (mean ± standard deviation) % of tryptase-positive mast cells coexpressed p16(INK4a). However, significantly higher percentage (86.0 ± 14.1%) of tryptase-positive tumor cells was immunoreactive to p16(INK4a) in all of 4 mastocytosis. The p16(INK4a) overexpression may induce the senescence of neoplastic mast cells to undergo spontaneous regression of mastocytosis.

Tumor thickness as a prognostic factor in extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a rare tumor and a widely accepted classification system specific for the disease has not been established. To elucidate prognostic factors of EMPD, we conducted a retrospective review of 145 patients with 155 EMPD lesions and investigated clinicopathological factors using univariate and multivariate analyses. We also explored tumor thickness and metastatic lymph nodes using detection analysis to determine cut-off points for survival. All patients were Japanese (88 men and 57 women), with EMPD in the genital (82.8%), perianal (3.4%) and axillary regions (1.4%). In the remaining cases (12.4%), there were lesions at two or more regions. Univariate analysis revealed the following prognostic factors: perianal location, presence of nodules, invasion depth, tumor thickness, number of metastatic nodes and serum carcinoembryonic antigen level. Both tumor thickness and perianal location retained statistical significance in multivariate analysis (hazard ratio, 1.39; 95% confidence interval, 1.12-1.72; P = 0.0024; hazard ratio, 50.72; 95% confidence interval, 4.20-612.63; P = 0.0020; respectively). The signal detection analysis indicated tumor thickness of more than 3 mm and three or more metastatic lymph nodes as cut-off points for survival. In conclusion, tumor thickness and the number of metastatic lymph nodes closely correlated with patient outcome and these factors could be suitable for the tumor and node classification.

Immunohistological Expression of p16INK4a is Commonly Present Both in Benign and Malignant Sweat Gland Neoplasias.

The expression of p16INK4a has been reported to be a significant marker for malignant transformation of epidermal tumors. However, little is known about sweat gland tumors. We examined the immunohistological expression of p16INK4a in benign and malignant sweat gland tumors. The ductal and acrosyringial portion of normal eccrine glands were positively stained with p16INK4a while it was negative in the normal epidermis. Moderate to strong expression of p16INK4a was found in 16 of 17 eccrine poromas, 4 of 5 hidradenomas, 3 of 3 syringocystadenoma papilliferums, 2 of 2 mixed tumors, and 3 of 3 syringomas. The p16INK4a expression was observed focally or diffusely in 4 of 4 porocarcinomas, 4 of 4 apocrine carcinomas and 12 of 17 extramammary Paget's diseases. We conclude that the p16INK4a expression is not a good marker for dictating malignant transformation of sweat gland tumors.

Localization of S100A2, S100A4, S100A6, S100A7, and S100P in the human hair follicle.

The hair follicle is a highly differentiated structure. In this study, we examined immunohistological localization of S100A2, S100A4, S100A6, S100A7, and S100P using specific monoclonal antibodies. S100A2 was strongly expressed in the entire outer-root sheath (ORS), but more weakly in cuticle and medulla in the bulb. S100A6, S100A7, and S100P were expressed in the innermost cells of ORS. The cuticular area was weakly positive for S100A2, S100A6, S100A7, and S100P. S100A4 was expressed in dendritic Langerhans cells and melanocytes. Sebaceous cells were variably immunopositive for S100A2, S100A6, and S100A7. A subset of dermal papilla cells expressed S100A4 and S100A6. None of the antibodies labeled the inner-root sheath. The distinct spatiostructural distributions of the S100 family proteins suggest that each protein is differentially involved in the physiological function of normal hair follicles.

Localization of S100A2, S100A4, S100A6, S100A7, and S100P in the human hair follicle.

The hair follicle is a highly differentiated structure. In this study, we examined immunohistological localization of S100A2, S100A4, S100A6, S100A7, and S100P using specific monoclonal antibodies. S100A2 was strongly expressed in the entire outer-root sheath (ORS), but more weakly in cuticle and medulla in the bulb. S100A6, S100A7, and S100P were expressed in the innermost cells of ORS. The cuticular area was weakly positive for S100A2, S100A6, S100A7, and S100P. S100A4 was expressed in dendritic Langerhans cells and melanocytes. Sebaceous cells were variably immunopositive for S100A2, S100A6, and S100A7. A subset of dermal papilla cells expressed S100A4 and S100A6. None of the antibodies labeled the inner-root sheath. The distinct spatiostructural distributions of the S100 family proteins suggest that each protein is differentially involved in the physiological function of normal hair follicles.

A library construction of 2,5-disubstituted pyrrole compounds by using solid/solution-phase syntheses.

Using solid- and solution-phase synthesis, a library of 2,5-disubstituted pyrrole compounds was constructed. This is the first report that Stetter reaction was applied to the solid-phase synthesis for C-C bond formation. Some of 2,5-disubstituted pyrrole compounds showed the inhibitory activity of LPS-induced mouse B-lymphocyte proliferation.