117 research outputs found

    RT-PCR tyrosinase expression in the peripheral blood of melanoma patients

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    Controversial data are reported in the literature concerning the role of peripheral blood tyrosinase messenger RNA reverse transcription PCR analysis in melanoma patient management. Some papers assess the clinical relationship between tyrosinase expression and disease outcome, while others address the high degree of variability in the positive rate percentage and demonstrate the transient shedding of melanoma cells in the bloodstream. An overview of the current knowledge about the applications and limitations of tyrosinase analysis compared with other biologic markers is presented herein. Tyrosinase expression should not be considered as a tumor burden-related marker in the peripheral blood, but rather as a measure of the potential increased risk of metastatic spreading. In this view, reverse transcription PCR gains a clinical significance when sequential determinations are performed during follow-up, whereas the evaluation of a single sample, either positive or negative, does not bring any additional clinical information

    Immature myeloid precursors in chronic neutrophilic dermatosis associated with myelodysplastic syndrome

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    Sweet syndrome (SS) associated with myeloproliferative disorders has been considered an inflammatory process mediated by neutrophils in which immunologic mechanisms are operative. The authors report the case of a 68-year-old man suffering from a myelodysplastic syndrome, who presented with a relapsing skin eruption resembling SS. Histopathologically, the skin infiltrates showed prominent neutrophilic features masking the underlying malignant process. Extensive immunophenotypic studies of skin revealed the presence of a few immature myeloid cells intermingled with an overwhelming infiltrate of neutrophils. The atypical cells in the skin had a phenotype identical to that of leukemic cells in the peripheral blood and bone marrow. Whether or not immature myeloid cell precursors constitute a specific infiltrate of leukemia cutis or are a result of recruitment of circulating leukemic cells to this area of inflammation is discussed

    CD45RA+ immunophenotype in mycosis fungoides: clinical, histological and immunophenotypical features in 22 patients.

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    BACKGROUND: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma (CTCL) usually characterized by a T-helper memory phenotype (CD3+, CD4+, CD8-, CD45R0+). Aberrant phenotypes are more commonly seen in the tumor stages. CD45RA expression has so far been documented in only a few cases of CD8+ or TCR gamma delta+ CTCL and in some pagetoid reticulosis cases. METHODS: Two hundred and fifteen MF patients were immunophenotyped in our laboratory between January 1992 and June 2000 and 22 cases of CD45RA+ MF (8.7%) were identified by immunohistochemical analysis. RESULTS: The majority of these CD45RA+ patients (20/22) showed a patch-plaque stage disease and an indolent clinical course, as expected in early-stage MF. The remaining 2 patients presented with stage IIB and IVA MF, and were characterized by an aggressive clinical course, with systemic spread. The immunohistochemical analysis revealed that CD45RA+ neoplastic cells belonged to the memory compartment, displaying a CD62L-, CD11a+, CD29+ phenotype. Most patients showed aberrant phenotypes, with a loss of T-cell lineage markers and expression of cytotoxic molecules or gamma-delta chain of the T-cell receptor. CONCLUSIONS: Our data show that CD45RA+ MF is a rare variant of CTCL and shares with the classic MF cases both the clinical features and disease course, even if it is characterized by a higher incidence of immunopathological abnormalities

    Role of RT-PCR tyrosinase detection in the monitoring of patients with advanced metastatic melanoma.

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    In recent studies a new method has been proposed to detect circulating melanoma cells in the peripheral blood of patients, based on the amplification of the mRNA for tyrosinase, an enzyme involved in melanin biosynthesis that is expressed only by melanocytic cells. The sensitivity and clinical relevance of this method are still controversial. In the present study, 596 blood samples from 186 melanoma patients at various clinical tumour stages, together with samples from 25 healthy volunteers, were analysed with the aim of investigating the value of tyrosinase detection in predicting melanoma recurrence. We suggest a possible role for this marker in the monitoring of melanoma patients after the excision of regional lymph node metastases, and provide evidence that tyrosinase is related to the status of disease in advanced metastatic patients. Moreover, chemotherapy administration appeared to influence tyrosinase determination and may explain the discrepancies in the reported percentages of positive samples

    Clinical significance of sequential tyrosinase expression in the peripheral blood of disease-free melanoma patients: a review of literature data

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    Data reported in the literature about the clinical significance of tyrosinase expression in the peripheral blood of disease-free melanoma patients are still controversial. In the study described here, a review of the papers specifically addressing the evaluation of the relationship between sequential RT-PCR assays during follow-up and clinical evidence of disease progression was performed; data collected were reported in terms of sensitivity and specificity, together with the results obtained at our institutions. A total of 861 stage I to IV melanoma patients were included, from seven studies. The overall sensitivity was 61% (range 24-100%). The overall specificity was higher than the sensitivity (76.5%), with values ranging from 48 up to 90.9%; two of the studies with higher specificity values included only stage III patients. The highest sensitivity and the lower specificity values were associated with the highest number of tyrosinase determinations per patient. In conclusion, tyrosinase RT-PCR is a potentially useful molecular marker, at least in the follow-up of stage III disease-free patients, only if assays are repeated every 2 or 3 months. We suggest carrying out radiological procedures at least after the second consecutive positive determination, even in the absence of clinical symptoms

    Expression of apoptosis markers on peripheral blood lymphocytes from patients with cutaneous T-cell lymphoma during extracorporeal photochemotherapy.

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    The mechanisms of extracorporeal photochemotherapy (ExP) therapeutic activity in cutaneous T-cell lymphomas (CTCLs) are not yet well understood, even though it has been suggested that a major mechanism may be induction of apoptosis. In vitro studies demonstrate that UVA-induced apoptosis is mediated by CD95-Fas expression and inhibited by Bcl-2 up-regulation and that UVA irradiation is able to down-regulate Bcl-2 expression. High-resolution multiparameter flow-cytometric analyses were used to evaluate Bcl-2/CD95-Fas expression on phenotypically identifiable circulating clonal T cells from 7 patients with CTCL (4 with SÚzary syndrome and 3 with mycosis fungoides with peripheral involvement) before and during ExP, in an attempt to ascertain whether Bcl-2/CD95-Fas status can be related to the hematologic response. A Bcl-2 normal phenotype before ExP or a normalization in Bcl-2 expression during ExP were related to a better clinical response, whereas a persistent Bcl-2 high expression was a negative prognostic factor. On the other hand, no response was found in patients with a CD95-Fas-negative phenotype, whereas the expression of CD95-Fas was associated with hematologic remission. Although further studies are needed to confirm these preliminary results, this study suggests that Bcl-2 and CD95-Fas expression could be evaluated, together with the other known clinical and immunologic factors, as additional parameters related to clinical response in patients with CTCL undergoing ExP

    Skin cancers and other cutaneous diseases in renal transplant recipients: a single Italian center observational study.

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    Kidney transplant recipients frequently suffer from skin infections and malignancies, due to the effects of long-term immunosuppressive therapy. Herein, a dermatological screening was performed to evaluate the relationship between risk factors, cutaneous tumours and other skin diseases in a group of 282 kidney transplant patients. Infectious diseases (16.7%) were the most frequent dermatological disorders, whereas cutaneous inflammatory and autoimmune diseases were relatively rare, probably due to an indirect therapeutic role of immunosuppressive regimens. Thirty patients experienced cutaneous side effects from immunosuppressants, mainly when receiving corticosteroids (p = 0.0372). We identified 99 patients (35.1%) who developed cutaneous tumours after transplantation. Cumulative tumour incidence was observed during long-term immunosuppressive therapy; no relationships were identified between skin cancer risk and single class of drug or combination regimens. When we evaluated the eventual relevance of other risk factors for skin cancers, we demonstrated a statistical significance in univariate analysis for male gender, more advanced age at transplantation, long duration of immunosuppressive regimens, no sunscreen usage, outdoor job, absence of cherry angiomas and presence of actinic keratoses (AKs). Age at transplantation (p = 0.0174), presence of AKs (p = 0.0005) and duration of immunosuppression (p = 0.0011) also confirmed their significance in multivariate analysis
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