Schwann cell differentiation of modified myoepithelial cells within adenoid cystic carcinomas and polymorphous low-grade adenocarcinomas: clinicopathologic assessment of immunohistochemical staining.

Adenoid cystic carcinomas and polymorphous low-grade adenocarcinomas have a known propensity for perineural invasion. Although modified myoepithelial cells have been shown to possess characteristics of a variety of cell types, they have not yet been found to mimic nerve tissue. Histologic evidence of Schwann cell differentiation would suggest the pathophysiologic mechanism by which these tumours exhibit neurotropism. An archival study of 41 specimens was performed to evaluate the Schwann cell staining properties of adenoid cystic and polymorphous low-grade adenocarcinomas using antibodies to S-100 protein, GFAP, neuron-specific enolase, and using a solochrome stain. Charts were reviewed to assess correlations between immunohistochemical and histochemical staining properties and various clinical parameters. The findings strongly suggest that neuronal differentiation does occur within these tumours. Furthermore, it was determined that solochrome positivity confers a significantly less favourable disease-free interval in these neoplasms. This new finding was highly statistically significant and has potential implications in the determination of prognosis for patients with these tumours.

Metallothionein as an epithelial proliferative compartment marker for DNA flow cytometry.

The antibody to the metal-binding low molecular weight protein metallothionein (MT) stains preferentially the proliferative edge of epithelial tumors in paraffin sections. The present report demonstrates its usefulness as an epithelial cell marker in DNA flow cytometry of archival specimens. Nine control breast (mammoplasty) specimens, 10 control colonic specimens (resection edges), 12 adenocarcinomas of breast, and 13 adenocarcinomas of colon were analyzed by DNA flow cytometry after MT and DNA staining. The average percentage of cells stained by MT ranged from 12% to 27% in these groups of specimens, which contain epithelial as well as stromal and inflammatory cells. Comparing cell turnover, measured as S-phase fraction (SPF) in unstained and MT-stained preparations, it was 10% and 20%, respectively, in control tissues and 10% and 30%, respectively, in adenocarcinomas. The SPF is lower in unstained preparations because of dilution by noncycling inflammatory and stromal cells. Immunohistochemical staining of various tissues for MT showed specific staining of epithelial cells. Evaluation of aneuploid malignant epithelial cells detected in six breast and eight colonic adenocarcinomas showed that on average, 47% of cells were stained with MT and that their SPF increased by about 50% when MT staining was compared with the unstained preparations. The results suggest that MT stains epithelial cells adequately for ploidy and cell cycle evaluation and that it may stain preferentially the proliferating cell compartment, which is considered to be an index of malignancy.

P-glycoprotein genes in the winter flounder, Pleuronectes americanus: isolation of two types of genomic clones carrying 3' terminal exons.

In mammals, P-glycoprotein (P-gp) is encoded by two or more highly conserved genes that differ in their abilities to transport drugs. One isoform class (class I) is consistently associated with the multidrug resistance phenotype, while the other (class III) is not. This study was designed to enumerate the P-gp genes in fish and determine how they are related to the two functional classes already defined in mammals. Southern blot analysis using a conserved single exon from the 3' terminal region of hamster P-gp cDNA (pEX1-172) as a probe indicated that there were two P-gp genes in right-eye flounders. Subsequently, two sets of clones were isolated from a winter flounder genomic library that correspond to the 3' ends of the two flounder P-gp genes. Sequence analysis was done on two key areas: the 3' ATP binding site and the 3' terminal exon, both of which were found to be homologous with their mammalian counterparts. Despite high levels of sequence identity in the predicted coding regions of the gene fragments it has not been possible to use these sequences to relate the homologs to particular mammalian classes of P-gp genes, perhaps because of gene conversion between mammalian P-gp genes. These cloned sequences are the first set of P-gp genes reported in lower vertebrates and will be useful for delineating the expression of P-gp genes in fish and understanding the role of P-gp in fish physiology.

Langerhans' cell histiocytosis in association with periapical granulomas and cysts.

This report describes a series of six cases of inflammatory periapical disease with small aggregates of Langerhans cells as a minor component. Immunohistochemical findings confirm that the cells are phenotypically related to Langerhans cells. Aggregates of these cells are not normally found in radicular cysts or periapical granulomas and have been interpreted to represent chronic localized Langerhans' cells histiocytosis. Whether these lesions, which arise within the context of chronic inflammatory periapical disease, represent incipient eosinophilic granulomas or are a more benign, minimally destructive form of Langerhans' cell histiocytosis is unknown. Clinical follow-up suggests that these lesions remain localized and that curettage is adequate treatment.