Cell discohesion and multifocality of carcinoma in situ of the bladder: new insight from the adhesion molecule profile (e-cadherin, Ep-CAM, and MUC1).

Urothelial cell carcinoma in situ (CIS) of the bladder is a superficially diffusive and highly discohesive disease. The authors analyzed the expression of some adhesion molecules (e-cadherin and Ep-CAM) and MUC1 in 32 unifocal and multifocal bladder urothelial cell CIS in an attempt to clarify this discohesion. E-cadherin was strongly expressed, in more than 75% of the cases. The presence of methylation of the CDH1 e-cadherin promoter gene was also investigated, but methylation was found in only one case. Ep-CAM was present in all the cases with a heterogeneous staining pattern. Similarly, MUC1/episialin was variously present in 94% of the cases without a polarized staining pattern and was expressed more strongly in cases with multifocal disease. Because loss of MUC1 polarization leads to interference with cell-cell adhesion mechanisms mediated by cadherins, these findings help explain why bladder urothelial cell CIS often shows a discohesive morphology and multifocality despite a strongly expressed adhesion molecule profile. Finally, Ep-CAM expression might provide some support for future target therapy trials.

Toker cells of the breast. Morphological and immunohistochemical characterization of 40 cases.

Toker cells are epithelial cells with clear cytoplasm usually free of cytologic atypia localized within the nipple epidermis. Rarely, they can be so numerous and atypical as to require a careful distinction from malignant cells of Paget's disease. The purpose of this paper was to better define the prevalence of these atypical Toker cells and to investigate phenotypic markers that can be helpful in the differential diagnosis with Paget's disease. Forty cases containing Toker cells were identified in the nipples of 390 patients (10.2%) who underwent complete breast mastectomy. In 24 cases (60%), Toker cells were cytologically bland and benign, disappearing after a few consecutive sections ("normal Toker cells"). In 11 cases (27.5%), Toker cells were more numerous and persistent on serial sections, still retaining bland cytologic features ("hyperplastic Toker cells"). In 5 cases (12.5%), hyperplastic Toker cells also became cytologically atypical ("hyperplastic and atypical Toker cells"). On immunohistochemistry, Toker cells were positive for estrogen (25/25) and progesterone (20/23) receptors, and negative for CD138 (18/19) and p53 (14/14); some hyperplastic and atypical Toker cells (4 cases) and hyperplastic Toker cells (1 case) showed faint immunoreactivity for HER2/NEU. For comparison, Paget's disease were negative for estrogen (6/10) and progesterone (7/10) receptors, and positive for CD138 (7/10), p53 (6/10), and HER2/NEU (9/10). Both Toker cells and Paget's disease stained positive for cytokeratin 7 and epithelial membrane antigen, and negative for p63. In conclusion, Toker cells are detectable in 10% of the nipples and are usually cytologically bland, but in 10% of the cases they can be morphologically atypical. The combined use of CD138/p53 is very helpful in distinguishing these atypical Toker cells from those of Paget's disease.

Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis.

UNLABELLED: Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, 15 LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70+/GPC3+ (59%) when a 2-marker panel was used. CONCLUSION: The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis.