Oncogenic BRAF mutations and p16 expression in melanocytic nevi and melanoma in the Polish population.

INTRODUCTION: Twenty-five - fifty percent of skin melanomas arise from nevi. Melanocyte proliferation is activated by BRAFV600E, then is arrested, but single nevi transform to melanomas. p16 controls arrest, and p16 loss may promote transformation. AIM: To analyze BRAFV600E, p16 expression and melanocyte proliferation in dermal, compound and dysplastic nevi, cells of primary and metastatic melanoma in the Polish population. MATERIAL AND METHODS: One hundred and thirty-two nevi (dermal, compound, dysplastic) and 41 melanomas (in situ, primary, metastatic) were studied. BRAF was assessed by cobas® 4800 BRAFV600 Mutation Test, High Resolution Melting Assay validated with: pyrosequencing and immunohistochemistry. p16 and Ki67 expression was analyzed by IHC. RESULTS: Eighty-two percent of nevi and 57% of melanomas display BRAFV600E expression. Most dermal and compound nevi had > 50% of p16(+) cells. BRAFV600E dysplastic nevi had a low number of p16(+) cells. Nevi without BRAFV600E (WT), had 90% of cells p16(+). In 60% of in situ and primary melanomas, there was a low number of cells of p16(+). Fifty percent of WT metastatic melanoma and 33% of BRAFV600E showed a high level of p16. The number of Ki67(+) cells in dysplastic nevi was very low. In 25% of BRAFV600E melanomas in situ and 55% of WT, > 10% cells were Ki67(+). All BRAFV600E primary melanomas and 66% of WT had > 10% Ki67(+) cells. Twenty percent of BRAFV600E and WT metastases had > 10% of Ki67(+), however, 62% of BRAFV600E and 32% of WT samples had > 50% of Ki67(+) cells. CONCLUSIONS: BRAFV600E and p16 are more frequent in nevi than in melanoma in vivo. A significantly higher p16 expression was observed in mutated nevi than in WT, while in melanoma it was just the opposite. The proliferation rate of melanoma cells negatively correlated with p16 expression.

Febrile neutropenia in a metastatic melanoma patient treated with ipilimumab - case report.

BACKGROUND: Ipilimumab is a fully human monoclonal antibody (mAb) targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab is currently approved in the U.S. and Europe for the treatment of metastatic melanoma in the first- and second-line treatment. Treatment with ipilimumab is linked to immune-related adverse events (irAEs) occurring in the majority of patients. These specific AEs include dermatitis, gastrointestinal disorders (diarrhea, colitis), hepatitis, hypophysitis, hypothyroidism, neuropathy, and iritis/inflammation of the ciliary body. CASE REPORT: We report a case of febrile neutropenia with agranulocytosis in the blood smear of a 35-year-old metastatic melanoma patient treated with ipilimumab 3 mg/kg. CONCLUSION: This AE was probably caused by antineutrophil antibodies associated with ipilimumab treatment. To our knowledge this is the first case report of febrile neutropenia in a metastatic melanoma patient treated with ipilimumab 3 mg/kg.

Skin pH is lower in type 1 diabetes subjects and is related to glycemic control of the disease.

BACKGROUND: Diabetes is a systemic disease affecting many organs, including skin. Skin may reflect the condition of internal organs. The aim of our study was to measure skin pH in type 1 diabetes mellitus (T1DM) patients and in healthy controls and to evaluate the association between metabolic control of diabetes and skin acidity in T1DM patients. MATERIALS AND METHODS: The study was conducted on 105 patients with T1DM and 53 age- and sex-matched healthy people. Skin surface pH was measured in three different areas of the body (cheek, forearm, and foot) in diabetes patients and healthy controls. The results were compared for patients' and controls' clinical characteristics and for patients' metabolic control and also evaluated according to the presence of complications of diabetes. RESULTS: Patients with T1DM had lower skin pH compared with the control group in three measured areas: within the cheek (5.49 ± 0.42 vs. 5.69 ± 0.31; P = 0.001), forearm (5.41 ± 0.46 vs. 5.73 ± 0.69; P = 0.004), and foot (5.20 ± 0.53 vs. 5.41 ± 0.41; P = 0.008). In the multiple linear regression skin pH was negatively correlated with fasting plasma glucose on the cheek (ß = -0.34, P = 0.0004), forearm (ß = -0.30, P = 0.0009), and foot (ß = -0.18, P = 0.04). Diabetes patients with glycated hemoglobin (HbA1c) ≥ 8% had significantly lower skin pH than patients with better glycemic control (HbA1c < 8%). However, we observed a statistically significant difference only on the foot (5.09 ± 0.50 vs. 5.34 ± 0.55; P = 0.019). CONCLUSIONS: Skin surface pH is lower in individuals with diabetes, and it is negatively related to actual and chronic hyperglycemia.

Resistance to vemurafenib can be reversible after treatment interruption: a case report of a metastatic melanoma patient.

About 40% to 60% of melanomas present BRAF mutation. Selective BRAF inhibitors such as vemurafenib and dabrafenib are currently approved for the treatment of advanced melanoma patients with BRAF mutation. The treatment-induced tumor regression occurs in the majority of patients; however, acquired resistance to BRAF inhibitors is observed in most of the patients after 6 to 7 months. After progression of the disease, the patient might be offered treatment with ipilimumab followed by chemotherapy. Subsequent lines of systemic treatment of metastatic melanoma patients do not exist.Here we report a case of a 59-year-old woman with a diagnosis of BRAF-mutant metastatic melanoma that responded to initial treatment with vemurafenib. Subsequently, after disease progression, the patient received chemotherapy. Since no clinical response to dacarbazine was observed, carboplatin with paclitaxel were applied. Transient partial response was obtained, which was followed by further disease progression. Then retreatment with vemurafenib was applied. The patient developed very short-term tumor regression and significant biochemical response (serum lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) to the treatment. However, following 5 weeks of retreatment, the patient developed progression of the disease. Our clinical observation indicates that in melanoma patients who developed resistance to selective BRAF inhibitors, rechallenge after treatment interruption might be beneficial.

Acne inversa goes an extra mile than hidradenitis suppurativa.

Acne inversa (AI, hidradenitis suppurativa, Velpeau's disease, Verneuil's disease) is a severe, chronic inflammatory dermatosis of unknown etiology, detected on the basis of clinical symptoms more frequently in women than in men. Purulent lesions in the form of nodules and inflammatory tumors, fistulas and scars are present in the areas with hair follicles and apocrine glands, most commonly on the armpits, groin, around the anus and pubic region. Acne inversa can lead to physical and mental disorders. Unfortunately, it is often misdiagnosed and ineffectively treated. The paper presents a case of a 46-year-old patient who was successfully treated surgically for AI around the anus and buttocks by excision of the changes and closure of the wound with local flaps and split-thickness skin grafts, taken with dermatome from the rear surface of the thighs. Surgical treatment is the method of choice in the treatment of severe AI.

New therapeutic options in systemic treatment of advanced cutaneous melanoma.

INTRODUCTION: For many years systemic treatment of advanced/metastatic melanoma has been based on chemotherapy or immunotherapy. However, even very toxic regimens (e.g., polychemotherapy, bio-chemotherapy or immunotherapy with HD-IL-2) despite increased response rates as compared with standard dacarbazine monotherapy have not improved patients' outcomes. Over the last two decades, a huge effort, made in order to determine the molecular and immunological mechanisms responsible for biology of melanoma led to development of novel targeted agents. AREAS COVERED: The aim of this article is to summarize data on novel targeted agents used for treatment of metastatic melanoma. The authors searched PubMed, EMBASE and abstracts from ASCO, ESMO, AACR congresses for Phase II/III clinical studies evaluating novel immunomodulating agents and kinase inhibitors in melanoma patients. EXPERT OPINION: Elucidation of the crucial role of MAPK pathway and BRAF kinase mutations in particular has led to development of specific small molecule kinase inhibitors (vemurafenib, dabrafenib, trametinib), and new insight into molecular mechanisms responsible for immune response and tolerance resulted in development of immunomodulatory agents (ipilimumab, anti-PD1, anti-PD-L1). The introduction of novel drugs has changed the natural history of melanoma. However, it has also generated new clinical challenges that have to be resolved as soon as possible.

Basal cell carcinoma - diagnosis.

Basal cell carcinoma is the most common skin cancer in the Caucasian population. The cancer arises in sun exposed areas of the skin. The incidence of morbidity is high and it is still growing. The metastatic rate is low, but the enlarging tumor may cause severe tissue disfigurement and a poor cosmetic outcome. The diagnosis is usually clinical but there are many subtypes of this carcinoma and correct diagnosis is the clue to appropriate treatment of the lesion. The main problem in basal cell carcinoma management is the high recurrence rate.

Co-occurrence of acanthosis nigricans and bladder adenocarcinoma - case report.

Acanthosis nigricans (AN) is characterized by the occurrence of symmetrical velvety hyperpigmented plaques that can be observed in each location on the skin. However, the lesions are most frequently located in the axillary, inguinal and nuchal areas. Primarily, the lesions appear as hyperpigmented focuses which later transform into papillary lesions. There are two forms of the disease - benign and malignant. Malignant AN is considered to represent paraneoplastic syndrome co-occurring with advanced cancer, but as such it is not malignant. This article presents a case of a patient diagnosed with AN and coexisting bladder cancer and discusses the case in the context of available literature.

Progress in the treatment of bone metastases in cancer patients.

INTRODUCTION: Bone metastases are a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer. Skeletal-related events involving pathological fractures, spinal cord compression and a need for surgery/radiotherapy, which are frequently observed in cancer patients with bone metastases have a detrimental effect on patients' survival and quality of life. Therefore, prevention of skeletal-related events is a crucial element in cancer treatment. AREAS COVERED: The aim of this article was to summarize data on bone-modifying agents used for treatment of cancer patients with bone metastases. We searched PubMed, EMBASE, and abstracts from ASCO, AUA, ESMO, AACR congresses for clinical studies evaluating bone-modulating agents in the treatment of patients with bone metastases. EXPERT OPINION: In breast cancer patients with bone metastasis, several bisphosphonates and denosumab demonstrated clinical efficacy. On the other hand, in patients with bone metastases from prostate cancer or other solid tumors only zoledronic acid and denosumab were clinically active. However, neither bisphosphonates nor denosumab have any positive impact on survival of patients with bone metastases. In a recent interim analysis of a Phase III clinical study, a novel bone-modulating agent - radium-223 chloride (alpharadin), a bone-seeking alpha emitter, has been demonstrated to significantly improve median overall survival of prostate cancer patients with bone metastases compared with placebo.

The 32nd Annual Meeting of German Society of Immunology. 26 - 29 September 2001.

The 32nd Annual Meeting of German Society of Immunology (DGfi) was held in Dresden on 26 - 29 September 2001. The philosophy of the meeting was 'to throw some light on the progress that had been made in transferring basic immunological research into clinical application'. More than 500 abstracts were submitted. The majority of abstracts were devoted to basic immunology but a large number dealt with clinical aspects of immunology. The organisers invited several distinguished speakers from USA but many of them did not come to Dresden due to the tragic events that occurred in America on September 11th. Here we present meeting highlights, which were mostly devoted to therapeutic aspects of immunology.

3rd international symposium on genetic anticancer agents.

The 3rd International Symposium on Genetic Anticancer Agents was an initiative of NDDO Research Foundation, which is an internationally operating organisation exclusively devoted to the research and development of new strategies for the treatment of cancer. The meeting focused on the preclinical and clinical development of various genetic agents for cancer treatment. Leading world experts came to Amsterdam to present recent results of their highly advanced research and to discuss novel approaches to cancer treatment. In addition to the scientific sessions, the organisers prepared an educational session devoted to the development process of a gene therapy product and to the design of clinical trials. The educational session aroused a great interest from the participants. The meeting highlights from different scientific sessions are presented.