Psoriasin (S100A7) is significantly up-regulated in human epithelial skin tumours

Abstract

Purpose: Psoriasin (S100A7) has originally been described to be expressed by psoriatic keratinocytes possibly as a result of altered differentiation and inflammation. As psoriasin was found to be overexpressed in human breast and bladder cancer suggesting a role in tumour progression, we investigated the expression of psoriasin in human epithelial skin tumours.

Methods: Realtime reverse transcription-polymerase chain reaction experiments were performed to analyse the mRNA-expression levels of psoriasin together with involucrin as a marker for epithelial differentiation and interleukin-8 (IL-8) as a marker for inflammation in skin biopsy samples from patients with precancerous skin lesions (PSL, n = 6), squamous cell carcinoma (SCC, n = 11), basal cell carcinoma (BCC, n = 17), and healthy controls (n = 10).

Results: Unexpectedly, mRNA expression levels for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) revealed a variation of up to 600-fold in all cDNA-samples under investigation, indicating that GAPDH is not suitable as a housekeeping gene in human skin samples. Psoriasin mRNA expression was significantly up-regulated in samples of PSL, SCC and BCC. In situ hybridisation and immunohistochemical examinations identified psoriasin mRNA and protein expression in the differentiated layers of the epidermis. IL-8 mRNA expression was significantly up-regulated in SCC, however, there was no correlation between elevated levels of psoriasin and the expression of IL-8.

Conclusion: Similar to the findings in breast and bladder cancer, the up-regulation of psoriasin might play a role in the progression of skin cancer. The expression of psoriasin in human skin tumours seems to be independent from differentiation and inflammation.

Fig. 1

RNA extraction from skin following an optimised protocol for sample preparation resulted in high-quality RNA. Demonstration of 14 representative samples obtained after total RNA extraction of skin biopsies. Integrity of 18S and 28S rRNA is shown after separation of 1 μg total RNA/sample in a 1% agarose gel with ethidium bromide staining

Fig. 2

Psoriasin mRNA expression is significantly up-regulated in PSL and in human epithelial skin cancer. The relative mRNA expression level was calculated relating to 10 ng RNA. The individual samples are represented by dots, the median is shown by a vertical bar in each group. NLS non-lesional skin, PSL precancerous skin lesions, SCC squamous cell carcinoma, BCC basal cell carcinoma. *p < 0.05, **p < 0.005, ***p < 0.0005

Fig. 3

Localisation of Psoriasin mRNA and Protein Expression in human epithelial skin cancer. In situ hybridisation (upper two panels) and immunohistochemistry analyses (lower two panels) were performed with skin samples obtained from non-lesional skin (NLS) from the same localisation as the tumour tissue (TU). A representative selection of each tumour entity is shown. Blue staining demonstrates specific in situ hybridisation of the antisense probe for psoriasin whereas red staining demonstrates positive psoriasin immunoreactivity in the differentiated epithelial layers (E) and in the hair follicles (HF) of NLS and more intensively within the tumour epithelium. AK actinic keratosis, SCC squamous cell carcinoma, BCC basal cell carcinoma, SG sebaceous gland, ESG eccrine sweat gland. Bar 100 μm

Fig. 4

Involucrin mRNA expression is not induced in PSL or human epithelial skin cancer. The relative mRNA-expression level was calculated for 10 ng RNA. Individual samples are represented by dots, the median is shown by a vertical bar within each group. The median relative involucrin mRNA expression showed no significant difference. NLS non-lesional skin, PSL precancerous skin lesions, SCC squamous cell carcinoma, BCC basal cell carcinoma

Fig. 5

Interleukin-8 mRNA-expression is significantly up-regulated in SCC of the skin. The relative mRNA-expression level was calculated for 10 ng RNA. The individual samples are represented by dots, the median is shown by a vertical bar in each group. NLS non-lesional skin, PSL precancerous skin lesions, SCC squamous cell carcinoma, BCC basal cell carcinoma. **p < 0.005