R.U. Peter

Antiapoptotic bcl-2 and bcl-xL in advanced malignant melanoma

Abstract Apoptosis is an important cofactor in the pathogenesis of a plethora of malignancies. However, little is known about modulation of the expression of bcl gene family in melanocytic tumors. To determine the role of bcl-2, bcl-x and bax in melanocytic tumors we investigated the differential expression of these genes via RT-PCR in tissue samples from human ¶benign nevi, primary melanomas and melanoma metastases in comparison with normal skin. Bcl-2 was strongly expressed in 14/16 metastases (87.5%), whereas only 7/13 primary melanomas (53%), 7/15 nevi (46%) and 7/16 normal tissue samples (43%) showed expression of bcl-2 ( P < 0.05). There was a strong indication of a correlation between tumor thickness and bcl-2 expression in nodular malignant melanomas. Expression of bcl-x was found in 16/16 melanoma metastases (100%), 11/13 primary melanomas (84%), 12/15 nevi (80%) and 10/16 normal tissue samples (62%) ( P < 0.05). Bcl-xL expression increased from primary melanoma to melanoma metastases, whereas bcl-xS showed a decreasing expression level during melanoma progression. No differences in bax expression were seen between melanoma metastases, primary melanoma, nevi and normal tissue. Immunohistochemical investigations of another 53 tissue samples showed similar results. Our results strongly indicate that bcl-2 and bcl-xL gene expression increases with progression of malignant melanoma. Bcl-2 and bcl-xL expression could reflect an increased malignant potential caused by an inhibition of apoptosis and growth advantage for metastatic melanoma cells.

Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer

The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR), HER2, HER3 and HER4 are involved in the pathogenesis of multiple human malignant neoplasias. However, their role in the carcinogenesis of basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) remains to be elucidated. In order to further define the role of these RTKs, 56 human skin tissue samples of normal skin, BCC and SCC were studied by conventional and differential and quantitative reverse transcriptase-polymerase chain reaction (rtPCR). EGFR and HER3 were predominantly expressed in the BCCs and SCCs, while HER2 was ubiquitously expressed. HER4 was not expressed in any sample. Since in vitro studies have provided compelling evidence that heterodimer formation of these receptors are associated with different signal transduction processes, coexpression patterns might be decisive for the induction and maintenance of a malignant phenotype. These results confirm this concept: isolated HER2 expression and EGFR/HER2 were predominantly found in normal skin, while HER2/HER3 and the triple expression of EGFR/HER2/HER3 were seen more frequently in the BCCs and SCCs compared with normal skin (50% and 40% compared with 26%, respectively). The activation of HER3, in addition to EGFR and HER2, might therefore be associated with the malignant phenotype. However, due to the small numbers in this study, further confirmation of the patterns is needed.

Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases

Amplification and overexpression of the c-myc gene have been associated with neoplastic transformation in a plethora of malignant tumours. We applied interphase fluorescence in situ hybridization (FISH) with a locus-specific probe for the c-myc gene (8q24) in combination with a corresponding chromosome 8 α-satellite probe to evaluate genetic alterations in 8 primary melanomas and 33 advanced melanomas and compared it to 12 melanocytic nevi, 7 safety margins and 2 cases of normal skin. Additionally, in metaphase spreads of 7 melanoma cell lines a whole chromosome 8 paint probe was used. We investigated the functionality of the c-myc gene by detecting c-myc RNA expression with RT-PCR and c-myc protein by immunohistochemistry. 4/8 primary melanomas and 11/33 melanoma metastases showed additional c-myc signals relative to the centromere of chromosome 8 copy number. None of the nevi, safety margins or normal skin samples demonstrated this gain. In 2/7 melanoma cell lines (C32 and WM 266–4) isochromosome 8q formation with a relative gain of c-myc copies and a loss of 8p was observed. The highest c-myc gene expression compared to GAPDH was found in melanoma metastases (17.5%). Nevi (6.6%) and primary melanomas (5.0%) expressed the c-myc gene on a lower level. 72.7% of the patients with c-myc extra copies had visceral melanoma metastases (UICC IV), patients without c-myc gain in 35.0% only. The collective with additional c-myc copies also expressed the gene on a significantly higher level. These results indicate that a c-myc gain in relation to the centromere 8 copy number might be associated with advanced cutaneous melanoma.

Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel ☆

BACKGROUND Narrow-band UVB (311 nm) phototherapy offering an emission spectrum closely conforming to the peak of the action spectrum for clearing psoriasis has significantly improved phototherapy for psoriasis. Because the majority of the commonly used topical therapies in treatment of psoriasis have limitations, a need for new topical agents remains. Tazarotene has been shown to be efficacious in plaque-type psoriasis. Combination of narrow-band UVB with topical agents has been shown to enhance efficacy of both treatment modalities. OBJECTIVE We attempted to evaluate the efficacy of narrow-band UVB phototherapy in combination with topical tazarotene. METHODS Ten patients with stable plaque psoriasis were treated with narrow-band UVB. In addition, topical tazarotene 0.05% was applied once daily to one side of the body. The follow-up period was 4 weeks. Efficacy was assessed separately for both body halves by means of a modified Psoriasis Area and Severity Index (PASI). RESULTS Both treatment modalities notably reduced the PASI scores with values being significantly lower in skin areas treated with narrow-band UVB phototherapy in combination with topical tazarotene. CONCLUSION The addition of tazarotene to narrow-band UVB phototherapy promotes more effective, faster clearing of psoriasis compared with UVB (311 nm) monotherapy.

Treatment of severe recalcitrant dermatoses of the palms and soles with PUVA-bath versus PUVA-cream therapy

PUVA‐bath therapy developed into a first line topical PUVA therapy, and gel and cream preparations have been described as alternative modes of topical 8‐MOP application. Because bath‐PUVA can be difficult to manage, topical PUVA therapy using 8‐MOP gel or cream preparations may become an important alternative when treating localised skin diseases. However, controlled comparisons of efficacy with this alternative topical PUVA therapy are lacking. We therefore compared the efficacy of PUVA‐cream therapy with PUVA‐bath therapy in 12 patients with recalcitrant dermatoses of the palms and soles using a left/right trial design. These patients responded well to both treatment modalities, meaning that both could be used successfully to treat recalcitrant dermatoses of the palms and soles.

Eosinophilic fasciitis treated with psoralen-ultraviolet A bath photochemotherapy

Eosinophilic fasciitis is a rare disorder which can markedly affect the quality of life in individual patients. So far, no generally accepted and effective treatment modality has been available. Although the precise nature of eosinophilic fasciitis is still unknown, it is often regarded as a variant of localized scleroderma (morphoea). Phototherapy and photochemotherapy have been shown to be effective in the treatment of sclerodermatous skin lesions. We report a patient with eosinophilic fasciitis which was successfully treated with psoralen plus ultraviolet A bath photochemotherapy within 6 months.

Late-type allergy to the X-ray contrast medium Solutrast (iopamidol).

In the past few years, there have been an increasing number of publications on delayed intolerance reactions, including rashes, following the use of X‐ray contrast media. We report a patient in whom infiltrated erythema of the face and generalized maculopapular rashes occurred on 2 occasions, within 1 day, following the use of the X‐ray contrast medium Solutrast® (iopamidol) for coronary angiography. The allergological investigations for clarification included prick tests and patch tests using a series of contrast media, as well as individual intravenous provocation tests. We found the cause to be a late‐type allergy to the active substance iopamidol contained in the contrast medium Solutrast®. We found a concomitant cross‐reactivity to the contrast media iopromid and iomeprol. All 3 contrast media represent the monomeric, non‐ionic type.

Psoralen plus ultraviolet-A-bath photochemotherapy as an adjunct treatment modality in cutaneous chronic graft versus host disease.

Background: Cutaneous chronic graft versus host disease (GVHD) is a severe complication following allogeneic stem cell (PBSCT) and bone marrow transplantation (BMT). Immunosuppressive therapy consists of prednisone, cyclosporine‐A, azathioprine or mycophenolate mofetil (MMF). Treatment of patients refractory to immunosuppression represents a major problem.

A pragmatic randomized controlled trial on the effectiveness of low concentrated saline spa water baths followed by ultraviolet B (UVB) compared to UVB only in moderate to severe psoriasis

Objective  To evaluate whether low concentrated saline spa water baths followed by ultraviolet B (LC‐SSW‐UVB) are superior to UVB alone in moderate to severe psoriasis.

Trauma and melanoma formation: a true association?

Background Little is known about the role of mechanical trauma in the pathogenesis of malignant melanoma. In individual patients, traumatic events have been discussed as a causative factor for the induction of melanoma and diagnosis of melanoma following trauma may raise medico‐legal questions. Objectives To evaluate the relationship between traumatic single or recurrent events and melanoma characteristics. Methods Retrospective questionnaire in 369 melanoma patients. Results A large number of patients (337 of 369; 91·3%) denied an association between a possible traumatic event and melanoma formation. Thirty‐two of 369 patients (8·7%) considered an association of trauma and melanoma formation likely. Of these 32 patients, 22 patients (13 men, nine women) reported a single event, and 10 patients (four men, six women) a persisting irritation. An irritation of a pre‐existing melanocytic naevus was reported by two patients with histologically confirmed melanoma on acquired or congenital naevus. Conclusions As most of the patients who mentioned a trauma in this study suffered from acral melanoma, or melanoma located on the extremities, a history of trauma should be expected more frequently at these body sites. A review of epidemiological, clinical and scientific research indicates that there seems to be no evidence for single or persistent traumatic events as a causative factor for melanoma formation.