Shrinkage of cutaneous specimens: formalin or other factors involved?

BACKGROUND: Shrinkage of cutaneous tissue during processing is a source of controversy. This study was designed to prospectively determine tissue shrinkage at two intervals: 1 min after excision and after 24 to 48 h of formalin fixation. Secondarily, gender, age, site, prior biopsy scar and solar elastosis were evaluated with respect to shrinkage. METHODS: Ninety-seven cutaneous specimens were measured prior to excision, 1 min after removal and after 24 to 48 h of formalin fixation. Width of prior biopsy scar, damage to elastic fibers and solar elastosis were subjectively quantified. RESULTS: Significant tissue shrinkage occurred immediately after excision, prior to formalin fixation. Mean shrinkage (95% confidence interval): length 20.66% +/- 2.15% and width 11.79% +/- 2.35%. Range of shrinkage: length 0 to 41.18% and width -18.75% (indicating expansion) to 37.50%. Patient age was significant; shrinkage decreased 0.3% per year of increasing age. Site was less significant; trunk excisions measured 5% greater shrinkage than head/neck excisions. As solar elastosis increased, shrinkage decreased. CONCLUSIONS: Cutaneous tissue shrinkage following excision is primarily because of intrinsic tissue contractility. Increasing patient age and solar elastosis correlate with less shrinkage. The clinicians and dermatopathologists must be cognizant of the expected shrinkage of submitted specimens for settling discrepancies within the medical record.

Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis.

BACKGROUND: Atopic dermatitis (AD) and psoriasis are the two most common chronic inflammatory skin diseases. Both of these diseases have distinct clinical findings and specific inflammatory cell infiltrates. Previous reports have focused individually on one or two genes or gene products in the lesions of both skin diseases. However, they have not captured the complex gene expression that must occur to induce specific cellular infiltrates in the skin lesions of these two diseases. DNA microarray studies allow the simultaneous comparison of thousands of messenger RNAs that may identify the disease-specific pattern of tissue inflammatory responses. OBJECTIVE: To compare the complex gene expression pattern of AD versus psoriasis skin lesions. METHODS: RNA was extracted from skin biopsy specimens of 6 patients with AD and 7 patients with psoriasis and analyzed with the use of Hu-U95Av.GeneChip microarrays. To confirm GeneChip results, real-time PCR of selected genes were performed. RESULTS: In AD skin, a total of 18 genes including the CC chemokines, CCL-13/MCP-4, CCL-18/PARC, and CCL-27/CTACK showed a statistically significant, >2-fold increase of gene expression compared with psoriasis. In psoriasis skin, a total of 62 genes including CCL-4/MIP-1beta, CCL-20/MIP-3alpha, CXCL-2/GRO-beta CXCL-8/IL-8, and CXCR2/IL-8R showed a >2-fold increase of gene expression compared with AD skin. Real-time PCR confirmed several of these GeneChip results. CONCLUSIONS: These results show a very distinctive gene expression pattern in AD as compared with psoriasis that may explain several features of AD and psoriasis including the specific inflammatory cell infiltrates observed in these disorders, that is, T(H)2 cells, eosinophils, and mast cells in AD and T(H)1 cells and neutrophils in psoriasis. Such observations may contribute to a characteristic "signature" for these two skin diseases.

Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes.

Atopic dermatitis (AD) and psoriasis are the two most common chronic skin diseases. However patients with AD, but not psoriasis, suffer from frequent skin infections. To understand the molecular basis for this phenomenon, skin biopsies from AD and psoriasis patients were analyzed using GeneChip microarrays. The expression of innate immune response genes, human beta defensin (HBD)-2, IL-8, and inducible NO synthetase (iNOS) was found to be decreased in AD, as compared with psoriasis, skin (HBD-2, p = 0.00021; IL-8, p = 0.044; iNOS, p = 0.016). Decreased expression of the novel antimicrobial peptide, HBD-3, was demonstrated at the mRNA level by real-time PCR (p = 0.0002) and at the protein level by immunohistochemistry (p = 0.0005). By real-time PCR, our data confirmed that AD, as compared with psoriasis, is associated with elevated skin production of Th2 cytokines and low levels of proinflammatory cytokines such as TNF-alpha, IFN-gamma, and IL-1beta. Because HBD-2, IL-8, and iNOS are known to be inhibited by Th2 cytokines, we examined the effects of IL-4 and IL-13 on HBD-3 expression in keratinocyte culture in vitro. We found that IL-13 and IL-4 inhibited TNF-alpha- and IFN-gamma-induced HBD-3 production. These studies indicate that decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-alpha and IFN-gamma under inflammatory conditions in AD skin. These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases.