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Primary Melanoma (primary + melanoma)

Distribution by Scientific Domains

Medical Sciences	93%
Life Sciences	6%

Distribution within Medical Sciences

Dermatology	77%
Oncology & Radiotherapy	9%
3 Other Subdomains	14%

Selected Abstracts

Interferon Alfa-2b or Not 2b?

DERMATOLOGIC SURGERY, Issue 1 2007
Significant Differences Exist in the Decision-Making Process between Melanoma Patients Who Accept or Decline High-Dose Adjuvant Interferon Alfa-2b Treatment
BACKGROUND Patients with thick (Breslow >4 mm) primary melanoma and/or regional nodal metastasis have a high risk of tumor recurrence. High-dose adjuvant interferon (IFN) alfa-2b offers ,10% improvement in relapse-free survival and overall survival with significant toxicity. OBJECTIVE The objective was to determine which prognostic factors and patient characteristics are significant in the decision to undergo IFN therapy. METHODS Of 781 patients who underwent sentinel lymph node (SLN) biopsy, 135 of 781 (17.3%) had positive SLN or thick melanomas and were informed of a ,50% risk of recurrence/disease-related mortality and offered IFN. Telephone surveys delineated reasons behind patients' decisions to accept IFN. RESULTS Acceptors, 60 of 135 (45%), decided to take IFN alfa-2b whereas 75 of 135 (55%) declined. Being female (OR, 2.4; 95% CI, 1.17,5.03; p=.017) and positive SLN status (OR, 2.2; 95% CI, 1.01,4.97; p=.048) were strongly associated with patients who chose IFN. Acceptors of IFN were younger, more influenced by physicians, and less affected by depression and side effect profile (p<.05 for all). Decliners were more concerned by strained relationships with family and social life (p<.05). CONCLUSIONS Gender and positive SLN were predictive of high-risk melanoma patients' acceptance of IFN treatment. Physician insight into melanoma patients' therapeutic decision-making process can guide patients through this difficult disease. [source]

Locoregional Cutaneous Metastases of Malignant Melanoma and their Management

DERMATOLOGIC SURGERY, Issue 2004
Ingrid H. Wolf MD
The correct classification of locoregional metastases of malignant melanoma to skin is central to the planning of treatment. Local recurrence means persistence of neoplastic cells at the local site by virtue of incomplete excision of the primary melanoma. Standard treatment is excisional surgery. In contrast, locoregional metastases of malignant melanoma (satellites, in-transit metastases) are metastases around a primary melanoma or between a primary melanoma and regional lymph nodes. They represent intralymphatic or hematogenous spread of neoplastic cells. We present a variety of available treatment options and discuss especially topical imiquimod as a novel approach for the palliative treatment of locoregional cutaneous melanoma metastases in selected patients. [source]

Detection of Micrometastasis in the Sentinel Lymph Node via Lymphoscintigraphy for a Patient With In-Transit Metastatic Melanoma

DERMATOLOGIC SURGERY, Issue 9 2003
Chih-Hsun Yang MD
Background. Lymphoscintigraphy and sentinel lymph node (SLN) biopsy are highly accurate methods of detecting regional lymph node status for melanoma. Previously, these procedures were mainly performed in patients with primary melanoma before wide local excision. Objective. To present a case with in-transit recurrence melanoma using lymphoscintigraphy and SLN biopsy for detection of nodal basin status. Methods. The patient discussed here had a subungual melanoma that developed as an in-transit metastatic melanoma on the pretibia area 2 years after right big toe amputation. By using lymphoscintigraphy and SLN biopsy technique with injection of technetium-99m colloid around the in-transit metastatic site, the first node (SLN) draining the in-transit metastatic tumor was identified and harvested on the right inguinal area. Immediate right inguinal node dissection was subsequently performed. Results. Under thorough histologic examination, the first node (SLN) draining the in-transit metastatic tumor was the only node that contained micrometastatic tumor cells in the surgical specimens. Conclusion. Lymphoscintigraphy and SLN biopsy techniques are sensitive procedures for detecting the regional nodal basin micrometastasis in in-transit recurrence melanoma patients. [source]

Cutaneous melanoma: interferon alpha adjuvant therapy for patients at high risk for recurrent disease

DERMATOLOGIC THERAPY, Issue 1 2006
Marko Lens
ABSTRACT:, Systemic adjuvant therapy in melanoma patients is the systemic treatment that is administered with the goal of eradicating micrometastatic deposits in patients who are clinically free of disease after surgical removal of the primary melanoma, but with a high risk of systemic recurrence. Interferon-alpha (IFN-,) is one of the most frequently used adjuvant therapies. Several randomized trials evaluated the efficacy of IFN-, in melanoma patients. However, results from conducted trials are controversial. Twelve randomized IFN-, trials are discussed in detail. All trials, including meta-analysis, failed to demonstrate a clear impact of IFN-, therapy on overall survival in melanoma patients. Based on currently available evidence, IFN-, therapy in the adjuvant setting should not be considered standard of care for patients who have melanoma. Results from ongoing studies are awaited. Further research for this therapy is required. [source]

Cutaneous melanoma: estimating survival and recurrence risk based on histopathologic features

DERMATOLOGIC THERAPY, Issue 5 2005
David E. Elder
ABSTRACT:, The prognosis of melanoma is best understood in terms of a model of tumor progression, in which most melanomas may evolve through two major phases of progression: from a lesion that is nontumorigenic and has little or no capacity for metastasis; to a more advanced lesion that is tumorigenic and may have capacity for metastasis. The likelihood of metastasis varies with a number of attributes of the primary melanoma, including the phase of progression, the Breslow tumor thickness, mitotic rate, and host response to the tumorigenic compartment of the lesion, Clark's level of invasion, and other factors. When distant metastasis has occurred, the prognosis for the patient is very poor. In this monograph, the focus will be the discussion of factors related to the prognosis of melanomas that at diagnosis are clinically localized to the primary site. [source]

Primary malignant melanoma in the oesophagus of a foal

EQUINE VETERINARY EDUCATION, Issue 8 2010
S. S. Caston
Summary A 2-month-old filly was evaluated for severe colic. Ultrasound, abdominocentesis and physical examination findings prompted an abdominal exploratory surgery. Perforation of the stomach was discovered during the surgery. The filly was humanely subjected to euthanasia under anaesthesia and post mortem examination was performed. In addition to gastric and duodenal ulceration, a thickened, black area of the proximal oesophagus was discovered. Histopathology of the lesion revealed primary malignant melanoma. Although rare, primary melanoma can occur in noncutaneous locations. [source]

Expression of the NKG2D ligand UL16 binding protein-1 (ULBP-1) on dendritic cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2006
David Schrama
Abstract Innate and adaptive immunity have not evolved separately. In this regard, the NKG2D molecule first identified on NK cells and classified as an activating NK cell receptor is also an important receptor for CD8+ T,cells. Functional analyses of human NKG2D and its ligands, i.e. UL16 binding proteins (ULBP) and MHC class I chain-related (MIC), have so far focused on immune cell-target cell situations because of the expression of NKG2D ligands on infected, stressed or transformed cells. Here, however, we address a possible function of NKG2D/ULBP-1 during the initiation of T cell responses. ULBP-1 can be detected on mature dendritic cells both in situ in the T cell areas of lymph nodes as well as in vitro after artificial maturation. FCM analysis further demonstrated that although NKG2D is expressed to some degree on all analyzed T cell subsets from peripheral blood, in vitro stimulation of T cells results in up-regulation of NKG2D on proliferating T cells. Using the sentinel lymph nodes of primary melanoma as a model for induction of defined T cell responses in vivo, we were able to demonstrate the expression of NKG2D on melanoma-associated antigen-specific T cells. Thus, our results suggest a role for NGK2D-ULBP-1 in the induction or reactivation of T cell responses. [source]

Tenascin-C in primary malignant melanoma of the skin

HISTOPATHOLOGY, Issue 4 2004
S Ilmonen
Aims :,To investigate the expression and the prognostic role of glycoprotein Tenascin-C (Tn-C) in primary melanoma of the skin. Methods and results :,The immunohistochemical expression of Tn-C was studied in 98 primary melanomas and related to inflammation, invasion, and patient outcome. Patients were followed up for disease recurrence for 0.04,7.4 years (median 3.9) and for survival for 0.5 to 12.1 years (median 9.3). The expression of Tn-C was evaluated for each tumour invasion border; the stromal and intracytoplasmic Tn-C of the melanoma islets were also recorded. Tn-C is widely expressed in primary melanoma samples, the staining pattern varying from focal to diffuse in different parts of the tumour. No correlation existed between intensity of Tn-C staining and inflammation. No stromal Tn-C was detected at the upper dermal lateral border in 12 patients, nor at the deep, dermal or subcutaneous border in 14 patients. These patients showed better disease-free survival (DFS) than did those cases with focal or diffuse staining (P = 0.06, P = 0.05). Also, absence of intracytoplasmic Tn-C was a beneficial prognostic factor for DFS (P = 0.04). In multivariate analysis, tumour ulceration and intracytoplasmic Tn-C expression of melanoma cells were independent adverse prognostic factors for DFS. Conclusions :,In primary melanoma of the skin, absence of Tn-C in the stroma of invasion fronts and within tumour cells seems to be related to a more benign disease behaviour with a lower risk of developing metastases. [source]

The increased expression of Y box-binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance

INTERNATIONAL JOURNAL OF CANCER, Issue 10 2007
Birgit Schittek
Abstract In previous studies we identified the transcription/translation factor Y-box-binding protein (YB-1) as a gene that is upregulated in primary melanoma and melanoma metastases when compared to benign melanocytic nevi. To analyze whether YB-1 expression correlates with melanoma progression in vitro and in vivo, we performed expression analysis on melanoma cell lines representing different stages of melanoma progression and on tissues of melanocytic nevi, primary melanoma and melanoma metastases. Our data indicate that compared to benign melanocytes YB-1 expression is increased in melanoma cells in vitro and in vivo and that YB-1 is translocated into the nucleus in invasive and metastatic melanoma cells. To reveal the functional role of YB-1 in melanoma progression we achieved a stable downregulation of YB-1 using shRNA in metastatic melanoma cells. Interestingly, YB-1 downregulation resulted in a pronounced reduced rate of proliferation and an increased rate of apoptotic cell death. In addition, migration and invasion of melanoma cells in monolayer and in a three-dimensional skin reconstruct in vitro was significantly reduced. These effects were accompanied by downregulation of genes involved in proliferation, survival and migration/invasion of melanoma cells such as MMP-2, bcl-2, Cyclin D1, p53 and p16INK4A. Furthermore, melanoma cells with a reduced YB-1 expression showed a decreased resistance to the chemotherapeutic agents cisplatin and etoposide. These data suggest that YB-1 is involved in malignant transformation of melanocytes and contributes to the stimulation of proliferation, tumor invasion, survival and chemoresistance. Thus, YB-1 may be a promising molecular target in melanoma therapy. © 2007 Wiley-Liss, Inc. [source]

Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship,

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2004
Qing Li
Background:, S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45SKP2 is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers. Methods:, Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed. Results:, Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 ± 0.2/85 ± 15) to melanoma in situ (3 ± 2/45 ± 20) to primary cutaneous melanoma (12 ± 9/30 ± 25) to metastatic melanoma (25 ± 15/15 ± 20) (p , 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p , 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = ,0.4, p = 0.0001). Skp2 cytoplasmic labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis. Conclusions:, Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle. [source]

Previous wide local excision of primary melanoma is not a contraindication for sentinel lymph node biopsy of the trunk and extremity,

JOURNAL OF SURGICAL ONCOLOGY, Issue 3 2003
Wey L. Leong MD
Abstract Background and Objectives The role of sentinel lymph node biopsy (SLNB) in patients with a previous wide local excision (WLE) was examined with case-control methodology. Methods A total of 168 consecutive cases of SLNB were performed in patients with truncal and extremity melanoma with tumor thickness of ,1 mm between October 1997 and June 2000 and were followed prospectively. For comparison, 65 of the103 SLNB patients referred to us after their WLE (cases) were matched by tumor thickness to 65 patients who had SLNB with concurrent WLE (controls). Radiocolloid (technetium-99m sulfur colloid) was used in all cases; in addition, vital blue dye (patent blue) was used in the control group. The two groups were followed for a median of 15.4 months. Results SLNs were identified in all patients with an average of 2.1 (cases) and 2.0 (controls) SLNs excised per patient (P,=,0.77). Twenty one (32.3%) of those having SLNB after previous WLE (cases) and 23 (35.4%) of those with concurrent WLE and SLNB (controls) were found to have metastatic disease in the SLN. The only false-negative in this group was detected in clinical follow-up in a patient whose truncal WLE was previously closed with a rotation flap (case). There was no significant difference in relapse-free survival (P,=,0.209) and overall survival (P,=,0.692) between groups. Conclusions SLNB is feasible in patients with previous WLE for extremity and truncal melanoma. Similar rates of sentinel positivity are found when compared with those in whom their WLE was done concurrently. J. Surg. Oncol. 2003;82:143,146. © 2003 Wiley-Liss, Inc. [source]

Sentinel lymph node biopsy in melanoma patients

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 9 2010
M Lens
Abstract Appropriate surgical management of regional lymph nodes is critical in patients with cutaneous melanoma. The use of intraoperative lymphatic mapping and sentinel lymph node biopsy (SLNB) has increased significantly in the past decade. SLNB is performed as minimally invasive procedure that provides accurate staging of melanoma patients with no clinically detectable nodal disease. In many melanoma units across the world, it became the standard for detection of occult regional node metastasis in patients with intermediate-thickness primary melanoma. Use of SLNB in patients with thin melanomas is still under evaluation. Although SLNB has been established as staging procedure in melanoma patients, its therapeutic role is still not clear. Large-scale ongoing randomized trials should elucidate whether SLNB with complete lymphadenectomy has a survival benefit in melanoma patients with early lymph node metastases compared to ,watch-and-wait' policy (observation). [source]

Comparison of metallothionein-overexpression with sentinel lymph node biopsy as prognostic factors in melanoma

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2007
G Weinlich
Abstract Background, Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. Immunohistochemical MT overexpression in paraffin-embedded tissues of patients with primary melanoma is associated with poor prognosis. While sentinel lymph node (SLN) biopsy is an established surgical technique for high-risk melanoma patients with predictive value for progression, the benefit of this procedure for the individual patient's overall survival remains unclear. Aim and methods, We examined the role of MT overexpression in comparison with SLN biopsy in melanoma patients as a prognostic marker for progression and survival. One hundred and fifty-eight (158) patients underwent SLN biopsy due to high-risk melanoma. Primary melanoma specimens were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. The patients were followed up (median 37 months); the data of disease free survival and overall survival were calculated with a broad panel of statistical analyses. Results, Twenty-eight (18%) out of 158 recruited melanoma patients developed metastases, 17 (11%) patients died due to widespread disease. Kaplan,Meier curves gave significant disadvantages for the MT-positive as well as the SLN-positive group for progression and survival. In the Fisher's exact test and Pearson's ,2 -test MT overexpression was highly significant for progression, whereas SLN biopsy failed significance. In univariate as well as multivariate Cox regression analysis MT overexpression proved an excellent marker for progression (P = 0.007 and P = 0.009), although the P -values for survival were not significant. In contrast, while in the univariate analysis SLN biopsy did not show significant results for progression it did for survival, and in the multivariate analysis reached a P -value < 0.05 for both measured endpoints. Conclusion, Results corroborate the validity of MT overexpression in primary melanoma as a useful prognostic marker in melanoma patients. Accuracy is comparable and to some degree supplementary to the results of SLN biopsy. [source]

Possible role of dermoscopy in the detection of a primary cutaneous melanoma of unknown origin

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2006
M Stante
Abstract For 2,8% of patients with metastatic melanoma, cutaneous and mucosal clinical examination does not lead to diagnosis of the primary tumour, which remains unknown. We report the case of a 41-year-old male patient who had received a diagnosis of metastatic melanoma after histological examination of an enlarged axillary lymph node, without previous detection of the primary lesion at his first dermatological examination. No pigmented skin lesions located in the anatomical area potentially drained by the affected axillary basin showed clinical features suggestive of a melanoma. Neither did the so-called ,ugly duckling' sign help us to identify the melanoma, because of the presence of a large number of clinically similar, common or slightly atypical melanocytic lesions located in that area. After dermoscopic examination we were able to narrow the field of possible candidates for excision to four lesions, selected on the basis of their dermoscopic features. Histological examination revealed the primary melanoma (superficial spreading melanoma (SSM), level III, thickness 0.5 mm) , located on the back , and three naevi with atypia. Preoperative distinction of the melanoma from the other three lesions was not possible because of the lack of well-established features of malignancy, even at dermoscopic analysis (,featureless' melanoma). Dermoscopy may thus play a role in the detection of a clinically unknown primary melanoma by narrowing the field of lesions to be removed for histological examination, saving many unnecessary excisions that would otherwise be inevitable. [source]

Induction of Primary Cutaneous Melanomas in C3H Mice by Combined Treatment with Ultraviolet Radiation, Ethanol and Aloe Emodin ,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2000
Faith M. Strickland
ABSTRACT The role of ultraviolet (UV) radiation in the induction of nonmelanoma skin cancer is widely accepted, although its precise contribution to the development of primary cutaneous melanoma skin cancer requires further definition. We found that painting aloe emodin, a trihydroxyanthraquinone from Aloe barbadensis, in ethyl alcohol vehicle on the skin of mice in conjunction with exposure to UVB (280,320 nm) radiation results in the development of melanin-containing skin tumors. C3H/HeN mice were treated thrice weekly with aloe emodin in a 25% ethanol in water vehicle and exposed to 15 kJ/m2 UV radiation. Neither ethanol vehicle nor aloe emodin alone induced skin tumors in the absence of UV radiation. In two separate experiments, 20,30% of the mice treated with a combination of UV radiation and ethanol vehicle and 50,67% of the UV-irradiated animals given aloe emodin in ethanol vehicle developed primary cutaneous melanin-containing tumors. The diagnosis of melanoma was established using Fontana silver stain for melanin; these tumors were negative for vimentin and keratin. Melanin-containing melanosomes were observed by transmission electron microscopy in tumors diagnosed as melanomas. Although the mechanism of carcinogenesis in these mice is currently unknown, our findings have led to the development of the first facile murine model for the induction of primary melanoma. This model has the potential to clarify the role of UV radiation in the etiology of malignant melanoma. [source]

Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting

BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2008
M.E. Vestergaard
Summary Background, Dermoscopy is a noninvasive technique that enables the clinician to perform direct microscopic examination of diagnostic features, not seen by the naked eye, in pigmented skin lesions. Diagnostic accuracy of dermoscopy has previously been assessed in meta-analyses including studies performed in experimental and clinical settings. Objectives, To assess the diagnostic accuracy of dermoscopy for the diagnosis of melanoma compared with naked eye examination by performing a meta-analysis exclusively on studies performed in a clinical setting. Methods, We searched for publications from 1987 to January 2008 and found nine eligible studies. The selected studies compare diagnostic accuracy of dermoscopy with naked eye examination using a valid reference test on consecutive patients with a defined clinical presentation, performed in a clinical setting. Hierarchical summary receiver operator curve analysis was used to estimate the relative diagnostic accuracy for clinical examination with, and without, the use of dermoscopy. Results, We found the relative diagnostic odds ratio for melanoma, for dermoscopy compared with naked eye examination, to be 15·6 [95% confidence interval (CI) 2·9,83·7, P = 0·016]; removal of two outlier studies changed this to 9·0 (95% CI 1·5,54·6, P = 0·03). Conclusions, Dermoscopy is more accurate than naked eye examination for the diagnosis of cutaneous melanoma in suspicious skin lesions when performed in the clinical setting. [source]

Sentinel lymph node biopsy in melanoma: a micromorphometric study relating to prognosis and completion lymph node dissection

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2007
S. Debarbieux
Summary Background, Sentinel lymph node (SLN) positivity has been found to be strongly associated with a poor prognosis in melanoma. Objectives, This large referral centre study was conducted: (i) to confirm the powerful prognostic value of SLN biopsy (SLNB); (ii) to correlate patient prognosis to the micromorphometric features of SLN metastasis in SLN-positive patients; and (iii) to correlate these micromorphometric features to the likelihood of positive completion lymph node dissection (CLND). Patients and methods, SLNB was performed in 455 cases of primary melanoma between January 1999 and December 2004; for patients with positive SLN, the following micromorphometric features were registered: size of the largest metastasis (two diameters), depth of metastasis, number of millimetric slices involved, maximum number of metastases on a single section, presence of intracapsular lymphatic invasion and extracapsular spread. Kaplan,Meier survival curves were compared with the log-rank test; multivariate analysis was performed using a Cox regression model. Dependence of CLND status on micromorphometric features of SLN was assessed by the ,2 test and predictive values of the different features were evaluated by multivariate analysis using a logistic regression model. Results, A positive SLN was identified in 98 of our 455 cases. Survival was significantly shorter in SLN-positive patients than in SLN-negative patients. Extracapsular invasion was found to be an independent prognostic factor of disease-free survival; ulceration of the primary and the maximum diameter of the largest metastasis were identified as independent predictive factors of disease-specific survival. Age and the lowest diameter of the largest metastasis were identified as independent predictive criteria of positive CLND, whereas depth of metastasis was not. Positivity of CLND was not significantly associated with a worse prognosis. Conclusions, Our study confirms the previously demonstrated strong prognostic value of SLNB. It also confirms the relationship between tumour burden in the SLN (evaluated by the maximum diameter of the largest metastasis) and clinical outcome. We point out a new micromorphometric feature of SLN, which seems to be predictive of CLND status: the lowest diameter of the largest metastasis. [source]

Tenascin-C in primary malignant melanoma of the skin

An unusual presentation of two simultaneous primary melanomas

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2006
Jashin J. Wu MD
No abstract is available for this article. [source]

Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor gamma during malignant melanoma progression

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 11 2008
Carolyn Lee
Background:, Cancer chemoprevention using nonsteroidal anti-inflammatory drugs is frequently attributed to cyclooxygenase-2 (COX-2) inhibition, although recent studies suggest that peroxisome proliferator-activated receptor gamma (PPAR,) may also be involved. While surgical excision remains the treatment mainstay for localized malignant melanoma, certain high-risk patients may benefit from adjunctive chemotherapy. In this study, we compared COX-2 and PPAR, immunohistological staining in benign nevi, primary melanomas and metastatic melanomas to help predict the effectiveness of compounds targeting these markers. Methods:, COX-2 and PPAR, immunohistological staining was performed and reviewed in 99 melanocytic lesions, including 38 benign nevi, 32 primary melanomas and 29 metastatic melanomas. Results:, There was a significant increase in both COX-2 and PPAR, immunostaining in melanomas compared with benign nevi. Metastatic melanomas were more likely to have a higher number of PPAR,-immunopositive cells. They were also more likely to express COX-2 than primary melanomas. Neither COX-2 nor PPAR, expression was associated with a specific pathologic subtype. Conclusions:, COX-2 and PPAR, may help modulate the progression of melanocytic precursor lesions to disseminated malignant melanoma. As such, they may serve as candidate substrates for targeted cancer therapies and may be particularly useful as adjuncts to surgery. [source]

Distribution of muscarinic receptor subtype M3 in melanomas and their metastases

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2008
Matthias Oppitz
Background:, Muscarinic acetylcholine receptors (mR) are involved in the regulation of cancer cell motility and cancer progression. mR have been shown in melanoma cell lines and cryostat sections of melanomas. To substantiate the experimental data, here the correlation of mR-expression with invasive growth was studied on the cellular level by comparison with HMB-45 immunoreactivity. Methods:, mR were detected by a M3 subtype-specific polyclonal antibody in normal skin, benign compound nevi, primary melanomas [nodular type, nodular malignant melanoma (NMM)] and metastases, and were compared with HMB-45 staining in parallel paraffin sections. Results:, The general staining pattern of anti-M3 and HMB-45 was similar with accentuation of zones with infiltrative growth. On the cellular level, only a subpopulation of the HMB-45 positive melanoma cells expressed mR. Immunoreactivity was encountered in 3 of 15 nevi, in 9 of 14 NMM and in 10 of 14 melanoma metastases. Polymorphonuclear granulocytes also exhibited strong reactivity for anti-M3. Conclusion:, mR-expression is associated with invasive migration of melanomas. [source]

Expression of activated Akt in benign nevi, Spitz nevi and melanomas

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2007
Sara M Kantrow
Background:, Activated Akt expression (p-Akt) is reportedly increased in many melanomas as compared with benign nevi. The purpose of this study was to evaluate and compare p-Akt immunohistological staining in benign nevi, Spitz nevi and primary melanomas. Methods:, Immunostaining for phosphorylated Akt was performed in 41 melanocytic lesions previously classified as benign intradermal nevus (14 lesions), Spitz nevus (9 lesions) or melanoma (18 lesions). Lesions were graded for intensity of p-Akt staining by two independent observers (0, no staining; 1, slightly positive; 2, moderately positive; 3, highly positive). Scores were averaged, and statistical analyses were performed. Results:, Benign nevi showed less staining (mean score 1.18) compared with Spitz nevi (mean score 2.11) and melanomas (mean score 2.19). This difference was statistically significant between benign nevi and melanomas (p = 0.0047) and benign nevi and Spitz nevi (p = 0.0271). No statistical difference was detected in staining between Spitz nevi and melanomas (p = 0.8309). Conclusions:, Activated Akt expression is increased in Spitz nevi and melanomas as compared with benign intradermal nevi, but is unlikely to prove useful in differentiating between the former. [source]

Phosphoinositide 3-kinase is not overexpressed in melanocytic lesions

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2007
Rajendra S. Singh
Background:, Although various studies have stressed the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-PI3K-AKT pathway in the progression of melanocytic lesions, little is known about the expression pattern of PI3K in these lesions. Objective:, To investigate the expression pattern of PI3K in benign and dysplastic nevi, primary melanomas, and metastatic melanomas and the role of PTEN and PI3K in melanocytic tumor progression. Methods:, Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 89 melanocytic lesions: 17 benign nevi, 18 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. Expression of PTEN and PI3K (p85 and p110 subunits) was evaluated immunohistochemically, and the number of cells and labeling intensity were assessed semiquantitatively. Results:, Both benign and dysplastic nevi showed strong cytoplasmic staining with PTEN, which was subsequently less in melanomas and completely lost in the metastatic lesions. Eleven of 17 (64%) benign nevi, seven of 10 (70%) dysplastic nevi, four of 23 (17%) primaries, and one of 31 (3%) visceral or lymph node metastasis showed strong positivity. Loss of PTEN expression from benign and dysplastic nevi to melanoma was statistically significant (p = 0.001). Although few cells showed reactivity for phosphoinositide 3-kinase (PI3 kinase)-p85 subunit, strong positivity was not detected in the cytoplasm of benign, malignant, or metastatic lesions, except for a single visceral metastasis. Three of 13 (23%) nevi showed positivity for the p110 subunit. No positivity was observed in the dysplastic nevi. Two of 22 (9%) melanomas, one of 14 (7%) visceral metastasis, and three of 12 (25%) lymph node metastasis showed strong positivity. There was no statistical difference in PI3 kinase expression in benign and malignant melanocytic lesions (p = 0.2). Conclusion:, PI3K is not overexpressed in melanocytic lesions. [source]

Protein expression of melanocyte growth factors (bFGF, SCF) and their receptors (FGFR-1, c-kit) in nevi and melanoma

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2007
K. A. Giehl
Background:, Basic fibroblast growth factor (bFGF) and stem cell factor (SCF) are essential growth factors for melanocytes which carry the receptors FGFR-1 for bFGF and c-kit for SCF. Because both factors may be involved in melanoma development, the expression of bFGF/FGFR-1 and SCF/c-kit was investigated in melanocytic tumors of different progression stages. Methods:, Fifty primary melanomas and 44 melanocytic nevi were analyzed for the expression of SCF, c-kit, bFGF, and FGFR-1 by immunohistochemistry. Results:, In melanoma, SCF and c-kit were expressed in 76 and 84%, respectively, and coexpressed in 66%. bFGF and FGFR-1 were expressed in 45 and 86%, respectively, and coexpressed in 46%. In melanocytic nevi, SCF was expressed in 23% and c-kit in 70% while coexpression was more common in dysplastic (39%) than non-dysplastic subtypes (8%). bFGF and FGFR-1 were expressed in 55 and 67%, respectively, while coexpression was found in 47% but varied considerably between different histological subtypes. Conclusions:, SCF and c-kit were frequently expressed by melanomas and dysplastic nevi suggesting an autocrine growth mechanism as described for bFGF. In both nevi and melanoma, c-kit was almost exclusively found in the epidermis while bFGF was more common in the dermis. Thus the growth factor/receptor expression seems to depend on the cutaneous localization of the melanocytic tumors. [source]

Chromogenic in situ hybridization analysis of melastatin mRNA expression in melanomas from American Joint Committee on Cancer stage I and II patients with recurrent melanoma

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2006
L. Hammock
Objective:, To determine whether loss of melastatin (MLSN) is a universal phenomenon in American Joint Committee on Cancer (AJCC) stage I and II melanoma patients who experienced recurrence. Material and methods:, Paraffin blocks of primary melanomas (PMs) were retrieved from 30 patients who had a negative sentinel lymph node biopsy and developed recurrent melanoma (AJCC stage I and II). Chromogenic in situ hybridization (CISH) methods were utilized to evaluate the expression of MLSN mRNA. These results were correlated with clinicopathologic data. Results:, Variable, heterogeneous expression of MLSN mRNA was identified in normal, in situ and invasive melanocytes within and between cases. For the invasive PM component, 24 (80%) had focal, regional or complete loss of MLSN mRNA. The remaining 20% had either regional or total partial downregulation of MLSN mRNA. Intact MLSN mRNA expression was present regionally in 14/30 (47%), with mean relative tumor area of 38%, range 5,85%. Increasing loss of MLSN mRNA significantly correlated with increasing tumor depth and microsatellites (r = 0.1/0.4, p = 0.04). However, thin, AJCC T stage 1a PM had higher relative mean loss than intermediate AJCC T stage 2a/2b/3a thickness PM (65% vs. 34%/48%/25%). Increasing loss of MLSN mRNA significantly impacted on disease free survival (DFS) by multivariate analysis (58 vs. 0% 2 years DFS, , 75 vs. >75% mRNA loss, p = 0.02). Decreased overall survival significantly correlated with increasing age and vascular invasion on multivariate analysis. Conclusion:, Extensive loss of MLSN in PM correlated with aggressive metastatic melanoma. Ancillary testing for MLSN mRNA expression by CISH could offer a means to more accurately identify AJCC stage I and II patients at risk for metastatic disease, who could benefit from adjuvant therapy. [source]

Loss of claudin-1 expression in tumor-associated vessels correlates with acquisition of metastatic phenotype in melanocytic neoplasms

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2005
Michael L. Cohn
Recent studies have suggested that some metastatic solid tumors lack claudin expression. It is unknown whether claudins play a role in cutaneous melanoma. Immunohistochemical studies were performed on tissue microarrays containing 19 benign melanocytic nevi (BN), 21 dysplastic nevi (DN), 23 primary malignant melanomas (MMs), and 31 metastatic melanomas (MMMs) using a polyclonal anti-claudin-1 antibody. Immunoreactivity in tumor cells and associated vessels was graded by intensity and by percentage of reactive cells. Normal epidermis served as internal control (3+ labeling). Cases with at least 2+ labeling in more than 25% of the cells were considered positive. Claudin-1 expression was present in 37% of BN, 24% of DN, 26% of MM, and 3.2% of MMM. Tumor-associated vessels showed the following results: 11 of 19 (58%) in BN, 14 of 21 (67%) in DN, 17 of 23 (74%) in MM, and 6 of 31 (19%) in MMM. A significant loss of expression was noted between MMM and all other lesions in tumor cells and associated vessels. There was no significant difference between BN, DN, and MM. Within primary melanomas, there was a significant correlation between expression of claudin in tumor cells and Clark level/Breslow thickness. Also significant was a decreased expression of claudin in tumor vessels of lesions with higher Breslow thickness or Clark level. These data suggest that loss of claudin-1 may play a significant role in the acquisition of metastatic phenotype in cutaneous melanoma. [source]

Pleiotrophin expression correlates with melanocytic tumor progression and metastatic potential

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2005
H. Wu
Background:, Gene expression profiling of melanoma and nevic tissue has demonstrated that pleiotrophin (PTN) is significantly overexpressed in human melanomas. Methods:, To further evaluate PTN expression in melanocytic lesions, protein immunohistochemistry was performed on the spectrum of melanocytic lesions. Results:, Melanocytic nevi were consistently negative (n = 58). In contrast, the great majority of metastatic melanomas were positive (33/34, 97%). The analysis of 34 primary melanomas demonstrated PTN positivity in 20 lesions while 14 lesions were negative. Within the primary melanomas, PTN immunoreactivity was associated with metastasis (p = 0.0004) and decreased melanoma-related survival (p = 0.0444). Univariate analysis of PTN immunoreactivity predicted an increased risk for metastasis (relative risk 9.1, p = 0.003). Conclusions:, The results of this study confirm previous gene profiling data showing differential PTN expression between melanocytic nevi and melanomas. In addition, lesional PTN expression is associated with metastatic potential and may be a prognostic factor for melanomas. [source]

BRAF V599E Mutation is Not Age Dependent: It is Present in Common Melanocytic Nevi in Both Children and Adults

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005
J. Cohen
BRAF encodes a serine-threonine kinase, which acts in the RAS/RAF/MAPK pathway transducing regulatory signals from RAS to MEK1/2. Somatic mutations in BRAF have been identified in 53,80% of primary melanomas and 70,90% of common melanocytic nevi. More than 90% of these mutations consist of a valine to glutamate substitution at codon 599 (V599E) of exon 15. While a high prevalence of BRAF mutations in common melanocytic nevi has been reported in adults, nevi in children have not been studied. Of interest, we have previously shown that Spitz nevi in children do not harbor mutations in BRAF. To investigate the association of BRAF mutations with patient age, we studied common melanocytic nevi in children for the V599E activating mutation. Tumor cells were microdissected from 6 common melanocytic nevi in children 10 years of age or younger, and analyzed for the V599E mutation in BRAF by allele-specific PCR and gel electrophoresis. In 6 of 6 (100%) nevi, the V599E mutant allele was observed. Our data suggest that similar genetic pathways are involved in the development of common melanocytic nevi in children and adults. The absence of BRAF mutations in Spitz nevi in children is therefore associated with tumor type, not patient age. [source]

Expression of insulin-like growth factor-binding protein 2 in melanocytic lesions

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2003
Huamin Wang
Background:, Insulin-like growth factor-1 (IGF-1) is one of the most critical proteins required for the survival, migration, and growth of melanoma cells. IGF-binding protein 2 (IGFBP2), which binds and regulates the function of IGF-1, is upregulated in a dose-dependent manner in melanoma cells treated with IGF-1, suggesting a possible role of IGFBP2 in the pathogenesis of melanoma. Methods:, Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 94 melanocytic lesions: 20 benign nevi, 20 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. IGFBP2 expression was evaluated immunohistochemically using a polyclonal antibody against the C-terminus of IGFBP2. The number of cells and labeling intensity were assessed semiquantitatively. Results:, Positive IGFBP2 labeling was observed in 5.0% of benign nevi, which was significantly lower than in dysplastic nevi (35.0%), primary melanomas (52.2%), or metastatic melanomas (54.8%) (p < 0.05). Among the IGFBP2-positive cases, moderate-to-strong immunostaining was observed in 64.7% of metastatic melanomas and 33.3% of primary melanomas. But none of the dysplastic nevi had moderate-to-strong immunostaining (p < 0.05). Conclusions:, Our study shows that IGFBP2 expression increases from benign and dysplastic nevi to primary and metastatic melanomas and suggests that it may play a role in melanoma progression. [source]

Nodular melanomas: Analysis of the casistic and relationship with thick melanomas and diagnostic delay

THE JOURNAL OF DERMATOLOGY, Issue 10 2008
Roberto BETTI
ABSTRACT The present study aimed to: (i) define thick melanomas related to nodular melanomas and other melanoma subgroups; and (ii) establish diagnostic delay in relation to the biological behavior of these melanomas and prevention programs. Cutaneous primary melanomas were studied. Nodular melanoma (NM), lentigo maligna melanoma (LMM) and superficial spreading melanoma (SSM) were selected. A further category named vertical growth melanoma (VGM) was also utilized. Analysis for sex, age, different values of thickness (1,2 mm, >2 mm; 1,3 mm, >3 mm; >4 mm), delay to diagnosis and patterns of detection were performed in all of the different subtypes. Eighty-seven patients with melanomas more than 1 mm of Breslow's thickness out of 506 melanoma were collected. Twenty-six were nodular cases, 39 SSM, five LMM and 17 VGM. Of those patients with NM, 42% had a thickness of more than 1,2 mm, 34% of 2,4 mm, 23% of more than 4 mm; and 54% with 1,3, 46% with more than 3 mm; and 58% with more than 2 mm. Even considering different values of thickness of more than 1 mm, a delay to diagnosis was significantly lower in NM (4.79 months) than in other subgroups. The value of more than 1 mm of Breslow's thickness may be sufficient to consider a melanoma to be thick. The lower diagnostic delay of NM suggests that they represent faster growing lesions probably with a different biological behavior than other melanoma subtypes. VGM should not be confused with NM, having a longer delay and different clinical features compared with the latter. They represent an area of diagnostic carelessness than potentially be improved. [source]