Immunohistochemical assessment of endothelin-1 axis in psoriasis, basal cell carcinoma and squamous cell carcinoma.

AIM: Endothelin-1 is an autocrine growth factor for keratinocytes, an effect controlled by its A and B receptors, with no previous comparison of endothelin axis expression in inflammatory and neoplastic skin diseases showing keratinocyte proliferation. The aim of the study was to investigate endothelin-1 axis expression in skin lesions of psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). METHODS: This study included 40 subjects (8 patients with SCC, 12 patients with BCC, 10 patients with psoriasis, and 10 healthy controls). Biopsies from lesional skin of patients and normal skin of controls were examined immunohistochemically for endothelin-1 and its receptors A and B frequency and grade of expression. RESULTS: Endothelin-1 and receptor A were detected in all patients with SCC and psoriasis, with a higher frequency and grade of expression than controls and BCC. The frequency of receptor B expression was significantly lower while higher staining grade was found in BCC (8.3%) rather than other studied groups. CONCLUSION: A comparable higher frequency and grade of expression of endothelin-1 and its receptor A are documented in psoriasis and SCC than in BCC and controls denoting their involvement in keratinocyte proliferation in both diseases. Receptor A is the predominately expressed receptor in psoriasis and SCC.

Vismodegib for the treatment of basal cell skin cancer.

PURPOSE: The pharmacology, clinical efficacy, adverse effects, cost, and place in therapy of vismodegib are reviewed. SUMMARY: Vismodegib, the first oral treatment for basal cell carcinoma (BCC), was recently approved for the treatment of patients with locally advanced or metastatic BCC whose cancer is refractory to standard treatments or who are not candidates for surgery or radiation. Vismodegib is a small molecule that potently inhibits signal transduction in the hedgehog signaling pathway, demonstrates nonlinear pharmacokinetics, and has a half-life of 13 days. Agents that increase gastrointestinal pH may reduce the solubility and bioavailability of vismodegib. It is effective in both locally advanced and metastatic BCCs, with response rates ranging from 30% to 60% in two clinical trials. Vismodegib is available as a 150-mg capsule, and the approved dosage is 150 mg orally once daily. The most common adverse effects of vismodegib include mild-to-moderate hair loss, muscle cramps, taste disturbance, and weight loss. The estimated cost of one month of treatment with vismodegib is $7500. CONCLUSION: Vismodegib was recently approved for the treatment of locally advanced or metastatic BCC that is refractory to standard treatments or if patients are not candidates for surgery or radiation. Vismodegib may have little effect on the treatment of BCC, given its high cost, the high cure rates achieved with standard therapies, and its unacceptable toxicity profile in patients with a non-life-threatening disease. However, vismodegib's novel mechanism of action, oral dosage form, preliminary efficacy, and tolerability compared with cytotoxic chemotherapy may make it an attractive candidate for the treatment of other cancers.

[Roles of immunohistochemistry in prognostic assessment of basal-like breast cancer].

OBJECTIVES: Basal cell-like breast cancer is one of the subtypes using molecular typing, and this subtype attracted a wide spread attention. Currently, no uniform diagnostic criteria are available. Most studies demonstrated poor outcomes, but contradictory conclusions appeared recently. The prognosis of basal cell-like breast cancer using different immunohistochemical criteria were analyzed. METHODS: Two hundred and eighty-four invasive breast cancers with a follow-up information over 5 years were evaluated for ER, PR, HER2, CK5/6, CK14, EGFR expression on tissue microarray immunohistochemically. Based on the results, these cases using four different diagnostic criteria were categorized, namely: Nielsen (ER-/HER2-, CK5/6+ and/or EGFR+), Kim (ER-/PR-/HER2-, CK5/6+ and/or CK14+ and/or EGFR+), Triple-negative (ER-/PR-/HER2-), and basal-CK (CK5/6+ and/or CK14+). 5-year survival information was compared between groups. RESULTS: The prevalence of basal cell-like breast cancer by Nielsen, Kim, Triple-negative and basal-CK were 15.5% (44/284), 14.8% (42/284), 43.3% (123/284) and 21.1% (60/284) respectively; the recurrence rates were 18.2% (8/44), 21.4% (9/42), 10.6% (13/123) and 11.7% (7/60) respectively. These were higher than recurrence rates for other subtypes, but only the differences by Nielsen's and Kim's criteria were significant. Using Nielsen's and Triple-negative's criteria, basal-like tumors showed shorter 5-year disease-free survival (both P < 0. 01) and overall survival (P < 0.05 and 0.01) than luminal A subtype, using Kim's criteria, basal-like tumors showed a lower 5-year disease-free but not overall survival than luminal A subtype (P < 0.01); no significant difference was found on 5-year survival between basal-like and non-basal-like tumors when typed by basal-CK. CONCLUSION: Basal cell-like breast cancers are more likely to show more recurrence and worse outcome, but different immunohistochemical diagnostic criteria have an influence on their prognostic analysis, so a uniform diagnostic criteria is essential for the further study of basal-like breast cancers.

Imiquimod: a review of basal cell carcinoma treatments.

Basal cell carcinoma (BCC) is regarded as the most prevalent malignant skin tumor in whites. A variety of surgical and nonsurgical interventions are available to treat BCC. In recent years, an immune response modifier drug, imiquimod, has been approved in treating superficial BCC (sBCC). The objective of the authors was to review the published literature to evaluate outcomes such as efficacy, safety, and quality of life associated with imiquimod treatment among patients with sBCC. A MEDLINE search of the literature was performed to identify studies published between January 1, 1995 and March 31, 2008 that evaluated imiquimod efficacy, safety, and quality of life in treating BCC. Overall, imiquimod 5% cream was associated with increased clinical and histologic clearance among patients with sBCC as compared to placebo. The findings from short-term cost effectiveness studies suggest that use of imiquimod 5% cream can be more cost-effective than surgical interventions such as excision surgery among patients with superficial BCC. Future studies evaluating long term cost effectiveness of imiquimod treatment are warranted.

An immunohistochemical study of lysozyme, CD-15 (Leu M1), and gross cystic disease fluid protein-15 in various skin tumors. Assessment of the specificity and sensitivity of markers of apocrine differentiation.

We investigated immunohistochemically the localization of lysozyme and Leu M1 in normal skin, 76 cases of benign sweat gland tumors, 28 cases of malignant sweat gland tumors, 23 cases of extramammary Paget's disease, 7 cases of sebaceous carcinoma, 6 cases of malignant trichilemmoma, 10 cases of squamous cell carcinoma, and 10 cases of basal cell carcinoma and compared the results with those for gross cystic disease fluid protein (GCDFP)-15 to assess the sensitivity and specificity of our assay conditions for apocrine differentiation. Normal apocrine glands were stained with all three antibodies, while eccrine glands were positive only for GCDFP-15, and other portions of normal skin were not stained with any of the antibodies used. In neoplastic tissue thought to be from apocrine tumors, antibodies raised against lysozyme and GCDFP-15 had a greater specificity (100%) for apocrine differentiation, while Leu M1 had a greater sensitivity (88%). Tissues that were stained with two or three of these antibodies appeared to exhibit apocrine differentiation. In the tumors examined, the specificity for apocrine differentiation was 100% and the sensitivity for such differentiation was 92% by these criteria. According to these criteria, some cases of syringocystadenoma papilliferum, primary mucinous carcinoma of the skin, and extramammary Paget's disease with underlying adenocarcinoma showed apocrine differentiation.