P63 and cytokeratin 8/18 expression in breast, atypical ductal hyperplasia, ductal carcinoma in situ and invasive duct carcinoma

The pattern and distribution of p63 expression as a myoepithelial/basal stem cell marker can be different between atypical ductal hyperplasia [ADH], ductal carcinoma in situ [DCIS] and invasive ductal carcinoma [IDC] and may denote basal phenotype of breast ductal carcinoma. CK8/18 is a luminal marker and may indicate a luminal phenotype of IDC and its expression in ADH and DCIS may refer to a possible precursor lesion to IDC. This work was designed to study and compare the expression of p63 and cytokeratin 8/18 [CK8/18] in some cases of ADH, DCIS and IDC. Histopathological evaluation and immunohistochemical study of anti-p63 and anti- CK8/18 was performed on selected archival cases of 7 ADH, 12 DCIS, 30 IDC of known clinicopathological data and previous estrogen receptor status [ER] for IDC. Confirmatory anti-smooth muscle actin [ASMA] expression for positive p63 cases was performed. p63 was expressed in the peripheral rim of the myoepithelial cell layer in ADH and DCIS with occasional gabs in DCIS. It was positive and stained occasional malignant cells in 3/30 [10%] of IDC cases. Confirmatory ASMA staining decorated the same peripheral rim of cells in ADH and DCIS, but was negative in p63 positive IDC cases. CK8/18 was positive in 100% of ADH, 8/12 [66.7%] of DCIS and 22/30 [73%] of IDC cases. Combined p63 and CK8/18 expression was noticed in 3/30 [10%] of IDC. It is concluded from this study that p63 is specific and valuable in differentiating myoepithelial cells and is more specific and valuable than other myoepithelial markers, as ASMA and can differentiate between ADH, DCIS, IDC as it stains peripheral myoepithelial cells in ADH and DCIS with gabs in the latter and does not stain any neoplastic cells. In IDC, it is positive in malignant cells in a minority of cases which may indicate basal/stem cell/myoepithelial cell origin of breast carcinoma. Comparatively, CK8/18 cannot differentiate ADH, DCIS and IDC as there is no difference in its staining pattern among them, which may suggest that they are a continuum or that ADH and DCIS are precursors for the luminal phenotype of IDC

Role of mast cells and cytokine profile [TNF-alpha, IFN-gmma, IL4 and IL-4 mRNA] in different types of leprosy

The aim of this study was to compare the number and the distribution of mast cells in biopsies taken in non reactional and reactional periods of the leprosy lesions. In addition, the expression of cytokines profile was analysed. 60 patients with leprosy were classified into three groups. Group I [non reactional leprosy included 38 patients, Group II [type I reaction] TIR included 13 patients, and Group III [type II reaction] TIJR included 9 patients. Cytokine profile was detected by determination of TNF-alpha, INF-gamma, IL-4 in the serum. In addition, IL-4 mRNA was determined in whole blood of all studied groups. Multiple punch biopsy specimens were taken from individual patients; for the examination of intra-lesional variation in mast cell numbers, specimens were taken from the centre of the lesion, the edge of tile lesion, and from the apparently unaffected skin outside the lesion at a point 2 cm from the nearest identifiable margin of the lesion. Comparison of INF-gamma and TNF-alpha in the sera of the different studied groups showed a significant difference between the groups, with a tendency to decrease in levels more in group III. Positive correlation between IFN-gamma and TNF-alpha, was detected. In addition, comparison of IL-4 and mRNA for IL-4 in the sera of the different studied groups showed a significant difference between the groups, with a tendency to increase in levels more in group III. Positive correlation between serum IL-4 and mRNA for IL-4, was observed. Density of mast cells in skin lesions of the different studied groups showed an insignificant difference between all groups as regards the centre of the lesion, while a significant difference was detected between group III and both groups I and II as regards mast cell density in the periphery and interstitium. The number of mast cells tends to increase from TT up to LL. A positive correlation was detected between mast cell density and IL-4 mRNA [r=0.57], while other studied cytokines did not show such a correlation. The cytokine profile is Th1 predominant in non reactional and TIR leprotic patients, while it shows Th2 predominance in TIIR leprotic patients. According to the pattern of cytokine production, mast cells are closely related to CD8+ T cells and IL-4mRNA leading to increased density of mast cells in skin lesions from TT up to LL, which in turn controls the out come of the disease