Tumour-cell-derived complement components C1r and C1s promote growth of cutaneous squamous cell carcinoma.

BACKGROUND: The incidence of epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. OBJECTIVES: To study the role of the complement classical pathway components C1q, C1r and C1s in the progression of cSCC. METHODS: The mRNA levels of C1Q subunits and C1R and C1S in cSCC cell lines, normal human epidermal keratinocytes, cSCC tumours in vivo and normal skin were analysed with quantitative real-time polymerase chain reaction. The production of C1r and C1s was determined with Western blotting. The expression of C1r and C1s in tissue samples in vivo was analysed with immunohistochemistry and further investigated in human cSCC xenografts by knocking down C1r and C1s. RESULTS: Significantly elevated C1R and C1S mRNA levels and production of C1r and C1s were detected in cSCC cells, compared with normal human epidermal keratinocytes. The mRNA levels of C1R and C1S were markedly elevated in cSCC tumours in vivo compared with normal skin. Abundant expression of C1r and C1s by tumour cells was detected in invasive sporadic cSCCs and recessive dystrophic epidermolysis bullosa-associated cSCCs, whereas the expression of C1r and C1s was lower in cSCC in situ, actinic keratosis and normal skin. Knockdown of C1r and C1s expression in cSCC cells inhibited activation of extracellular signal-related kinase 1/2 and Akt, promoted apoptosis of cSCC cells and significantly suppressed growth and vascularization of human cSCC xenograft tumours in vivo. CONCLUSIONS: These results provide evidence for the role of tumour-cell-derived C1r and C1s in the progression of cSCC and identify them as biomarkers and putative therapeutic targets in cSCC. What's already known about this topic? The incidences of actinic keratosis, cutaneous squamous cell carcinoma (cSCC) in situ and invasive cSCC are increasing globally. Few specific biomarkers for progression of cSCC have been identified, and no biological markers are in clinical use to predict the aggressiveness of actinic keratosis, cSCC in situ and invasive cSCC. What does this study add? Our results provide novel evidence for the role of complement classical pathway components C1r and C1s in the progression of cSCC. What is the translational message? Our results identify complement classical pathway components C1r and C1s as biomarkers and putative therapeutic targets in cSCC.

Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma.

PURPOSE: The two main etiological factors for vulvar squamous cell carcinoma (vSCC) are the vulvar dermatosis lichen sclerosus (LS) and high-risk human papillomavirus (hrHPV). Serpin A1 (α1-antitrypsin) is a serine protease inhibitor, which plays a role in the tumorigenesis of various cancer types. The aim of the study was to evaluate the expressions of Serpin A1 in LS, premalignant vulvar lesions, and vSCC using immunohistochemistry (IHC) and serum analysis, and to compare Serpin A1 stainings to the tumor markers p53 and p16. METHODS: In total, 120 samples from 74 patients were studied with IHC for Serpin A1, p53 and p16: 18 normal vulvar skin, 53 LS, 9 premalignant vulvar lesions (dVIN/HSIL) and 40 vSCC samples. Serum concentrations of Serpin A1 were analyzed from 30 LS, 44 vSCC and 10 control patients. Expressions were compared to clinical data. RESULTS: Tumor cell-specific Serpin A1 overexpression was detected in 88% of vSCC samples, independent of the etiology. The intensity of Serpin A1 expression was significantly higher in vSCC than in healthy vulvar skin, LS, or premalignant vulvar lesions. Serpin A1 showed an association with p53 positivity. No difference in overall survival was found between Serpin A1-, p53-, or p16-positive vSCC patients. Serum concentrations of Serpin A1 were equal in the LS, vSCC, and control groups. CONCLUSION: Tumor cell-specific Serpin A1 overexpression is a potential biomarker in vSCC.

Serum lipid level in Iranian patients with psoriasis.

BACKGROUND: Psoriasis is a common, chronic, inflammatory and proliferative skin disease associated with abnormal lipid metabolism. Previous studies have demonstrated that patients with psoriasis may have an increased risk of occlusive vascular disease. OBJECTIVES: The aim of this study was to determine lipid profile in Iranian patients with psoriasis. SUBJECTS AND METHODS: A cross-sectional study was performed in 30 patients with approved psoriasis diagnosis attending the Dermatology Outpatient Department at Sina Hospital, Hamedan, Iran and 30 matched healthy individuals. Fasting blood sugar (FBS), triglyceride, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) were measured using standard enzymatic method. The psoriasis activity was evaluated by psoriasis area and severity index (PASI Index). RESULTS: FBS levels were higher in patients with psoriasis diagnosis but the differences were not significant (P-value = 0.284). There were no significant differences between serum levels of triglyceride and cholesterol in two groups. There were no differences in lipoproteins (HDL, LDL, VLDL) compared with control subjects. (P-value > 0.05) PASI Index and lipid profile did not have any significant correlation. The correlation between duration of disease and LDL were significant (P-value = 0.033). CONCLUSION: Lipid profile in Iranian patients with psoriasis did not differ compared with control-matched subjects.

A study of dermatophytoses in Hamadan, the governmentship of West Iran.

In order to determine the extent and causative agents of dermatophytoses in the Hamadan region of West Iran; a study was made during a 9-month period from October 1991 to June 1992. A total of 7495 individuals were studied of whom 681 (9%) were suspect of having cutaneous mycoses. Among them dermatophytoses were the commonest infections (259/681 = 38%). Of 259 individuals infected with dermatophytes, tinea capitis were observed in 163 (62.9%); t. corporis in 27 (10.4%); t. manuum and t. cruris in 19 (7.3%) each; t. barbae and faciei in 14 (5.4%); t. pedis in 13 (5%) and t. unguium in 4 (1.5%). A total of 144 patients yielded dermatophyte cultures. The frequency of the isolated species in decreasing order was as follows: Trichophyton verrucosum, 78 (54.1%); T. schoenleinii, 48 (33.3%); Microsporum canis, 8 (5.5%); Epidermophyton floccosum, 5 (3.5%); T. mentagrophytes and M. gypseum, 2 (1.4%) each; T. tonsurans, 1 (0.7%). In conclusion, the most prevalent dermatophytosis in this region was t. capitis with the infecting agent of T. schoenleinii.