Role of integrin alpha 2 beta 1 (VLA-2) in the migration of human melanoma cells on laminin and type IV collagen.

The random cell migration of four human melanoma cell lines on laminin and type IV collagen-coated substrates was studied by video time-lapse image analysis and compared to the expression of a number of beta 1 integrins including alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1 using flow cytometry. These integrins were heterogeneously expressed in the four cell lines tested with three of four lines expressing alpha 2 beta 1. The melanoma cell line that did not express alpha 2 beta 1 exhibited weak attachment and low cell migration rate on both laminin and type IV collagen, whereas the other melanoma cell lines showed an increase in attachment and mean cell migration rate in a dose-dependent manner on the matrix molecules (p < 0.001). The enhanced migration seen in the three cell lines could be specifically inhibited by function blocking anti-beta 1 and anti-alpha 2 monoclonal antibodies (p < 0.001) but not by function blocking anti-alpha 3 and anti-alpha 6 monoclonal antibodies. Image analysis of the cells before and after treatment with anti-beta 1 and anti-alpha 2 MoAb indicated that the inhibition of migration did not result in detectable cell detachment, retraction of cell processes, or other significant cell-shape change. Taken together, the findings suggest that the observable enhanced migration on laminin and type IV collagen of a number of human melanoma cell lines is largely mediated by integrin alpha 2 beta 1.

Juvenile xanthogranuloma. Clinical and pathologic characterization.

The changing name of the juvenile xanthogranuloma bears witness to the evolution of knowledge and experience of its varied clinical and histologic presentations. This study characterizes the clinical, microscopic, and some immunohistochemical features of 34 cases. The salient clinical findings include a bimodal age distribution inclusive of adults, a male:female ratio of 4:1, occasional multiplicity of lesions (20%), and common presentation in the cephalad area. Histologic findings include varied architectural patterns, cellular participation in various proportions by foamy histiocytes, epithelioid monocytes, lymphocytes, plasma cells, eosinophils, Touton giant cells, and spindle cells of two forms (dendritic and fusiform). S100-positive dendritic cells comprised a minor, but important, component at expansion zones. The significance of these findings is described.

DNA flow cytometry of primary tumors and their skin metastases. Correlation of DNA histograms.

The purpose of this study was to determine whether quantification of DNA content would demonstrate conserved patterns in primary tumors and their metastases and to learn whether this technique would be useful in determining if a tumor was metastatic from a previous primary tumor or represented a new neoplasm. The study comprised of all cases nonmelanoma metastatic skin lesions in which the primary tumor was also resected at this hospital between the years 1984 and 1990 (22 cases). Both the primary and metastatic lesions were examined by the deparaffinized flow cytometric technique for DNA content. DNA-aneuploid tumors were considered to correlate if the DNA indices (ratio of aneuploid to diploid peak channels) were within 10%. Thirty-four tumors were DNA-aneuploid; eight tumors were DNA-diploid. We found agreement in 20 of 22 cases (agree--aneuploid: 16 cases; agree--diploid: four cases). In six of our cases the histograms of the primary and the metastatic lesions did not correlate when only one block was examined; however, when three blocks from each site were studied, we found concordance of DNA indices in four cases. There was disagreement in two of 22 cases (disagree--different DNA indices: two cases). In both of these cases, only one block of the primary tumor was available for examination, and the histograms were of marginal quality. This study demonstrates that the histogram pattern (aneuploid versus diploid) of DNA content is highly conserved between primary and metastatic tumors. There was 91% agreement between DNA indices of primary tumors and their metastases (20 of 22 cases) using a 10% correlation criterion.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA flow cytometry of epithelioid sarcoma.

DNA ploidy of paraffin-embedded tissue from 11 patients with epithelioid sarcoma and 20 control specimens (granuloma annulare and sarcoid) was studied. DNA aneuploidy was found in 64% of the epithelioid sarcomas and in none of the control samples. Aneuploidy did not correlate with necrosis, vascular invasion, or mitotic rate. There was also no association of aneuploidy with adverse outcome.

Aneuploidy in pancreatic insulinomas does not predict malignancy.

Nuclear deoxyribonucleic acid (DNA) ploidy studies with paraffin embedded archival material from 14 pancreatic insulinomas were performed by flow cytometry. Clinical follow-up (2 to 17 years; mean, 8 years) was obtained for all patients. Half of the tumors had a normal DNA histogram and half exhibited an abnormal DNA profile consistent with DNA aneuploidy. Six of the seven patients with aneuploid tumors are alive and disease free (2 to 5 years postresection), and one is alive with metastatic disease. Of the seven patients with tumors showing normal DNA profiles, five are alive and disease free, one is dead of disease, and one is alive with metastatic disease. These data suggest that DNA ploidy analysis is unlikely to provide useful prognostic information for patients with insulinomas.

Application of DNA flow cytometry from paraffin-embedded tissue to the diagnosis of mycosis fungoides.

The distinction of mycosis fungoides from benign inflammatory lesions is sometimes difficult by conventional histological techniques. Aneuploidy, a feature often associated with malignant tumors, can be assessed even in tissue routinely processed in paraffin using the flow cytometric technique of Hedley and associates. In many tumor systems, there are significant diploid clones. We have evaluated the flow cytometric DNA ploidy of paraffin-embedded tissue in the diagnosis and prognosis of mycosis fungoides (MF). We studied 22 cases of MF and 10 control cases of inflammatory skin lesions with epidermal involvement. Aneuploidy was found in 27% of the MF cases, but in none of the controls (ED). Aneuploid features were seen in 23% of tissues from early stage disease. Aneuploidy did not correlate with atypia, epidermotropism, or number of mitoses. There was a trend towards showing adverse outcome in those patients with aneuploid lesions. The detection of aneuploidy might be helpful for early diagnosis of MF.