Diagnosis Of Primary Cutaneous Melanoma Research Articles

Clinical Impact and Accuracy of Shave Biopsy for Initial Diagnosis of Cutaneous Melanoma

IntroductionEffective treatment of malignant melanomas is dependent upon accurate histopathological staging of preoperative biopsy specimens. While narrow excision is the gold standard for melanoma diagnosis, superficial shave biopsies have become the preferred method by dermatologists but may transect the lesion and result in inaccurate Breslow thickness assessment. This is a retrospective cohort study evaluating an initial method of biopsy for diagnosis of cutaneous melanoma and indication for reoperation based on inaccurate initial T-staging. MethodsWe retrospectively analyzed consecutive patients referred to the Medical College of Wisconsin, a tertiary cancer center, with a diagnosis of primary cutaneous melanoma. Adult patients seen between 2015 and 2018 were included. Fisher's exact test was used to assess the association between method of initial biopsy and need for unplanned reoperation. ResultsThree hundred twenty three patients with cutaneous melanoma from the head and neck (H&N, n = 101, 31%), trunk (n = 90, 15%), upper extremity (n = 84, 26%), and lower extremity (n = 48, 28%) were analyzed. Median Breslow thickness was 0.54 mm (interquartile range = 0.65). Shave biopsy was the method of initial biopsy in 244 (76%), excision in 23 (7%), and punch biopsy in 56 (17%). Thirty nine (33%) shave biopsies had a positive deep margin, as did seven (23%) punch biopsies and 0 excisional biopsies. Residual melanoma at definitive excision was found in 131 (42.5%) of all surgical specimens: 95 (40.6%) shave biopsy patients, 32 (60.4%) punch biopsy patients, and four (19.0%) excision biopsy patients. Recommendations for excision margin or sentinel lymph node biopsy changed in 15 (6%) shave biopsy patients and five (9%) punch biopsy patients. ConclusionsShave biopsy is the most frequent method of diagnosis of cutaneous melanoma in the modern era. While shave and punch biopsies may underestimate true T-stage, there was no difference in need for reoperation due to T-upstaging based on initial biopsy type, supporting current diagnostic practices. Partial biopsies can thus be used to guide appropriate treatment and definitive wide local excision when adjusting for understaging.

Impact of the SARS-CoV-2 pandemic on the diagnosis of primary cutaneous melanoma at a University Hospital in Rio de Janeiro

Impact of the SARS-CoV-2 pandemic on the diagnosis of primary cutaneous melanoma at a University Hospital in Rio de Janeiro

59 Associations of Biological Sex with Clinicopathologic Features of Cutaneous Melanoma

Abstract Aim It is commonly known that women have better prognosis than men after diagnosis of primary cutaneous melanoma. However, few studies have investigated whether histopathological prognostic factors are associated with this difference. This study aimed to investigate if there were sex-specific differences in prognostic features of primary melanoma at time of diagnosis in a large clinical series. Method This was a records-based observational study of unselected patients treated for melanoma in a major tertiary oncology centre in the United Kingdoms, 2002–2016. Prognostic features (age at diagnosis; thickness of primary melanoma; ulceration and mitotic count) were extracted from histological reports and sex-specific differences tested for significance using X2 test. Results Among 1323 melanoma patients of median age 61 years (range 15–99), and roughly equal proportions of males (640, 48%) and females (683,52%), females had significantly earlier age of presentation on average than males (58 vs 64 years) (p<0.001). Comparing Breslow thickness of <2mm vs ≥2mm, significantly more females (414, 67%) than males (282, 55%) had melanomas <2mm (p<0.001). Other key histopathological factors namely presence of ulceration (p=0.073) and mitotic rate (p=0.618) were not significantly different by sex. Conclusions We found that female melanoma patients presented at an earlier age and with thinner primary melanomas than males, but mitotic rate (speed of tumour growth) was not significantly different. These data suggest that females’ better prognosis is explained by their tendency to present earlier with suspicious skin lesions than males.

Reporting regression in primary cutaneous melanoma. Part 1: history, histological criteria and pathogenesis.

Regression is an important histopathological parameter reported for the diagnosis of primary cutaneous melanoma. Histological regression is defined by The College of American Pathologists as the replacement of tumour cells by lymphocytic inflammation, with attenuation of the epidermis, and nonlaminated dermal fibrosis with inflammatory cells, melanophagocytosis and telangiectasia. Histological regression may be reported as absent versus present and, if present, as complete, partial or segmental. The stages of histological regression are early, intermediate and late, depending on the extent of histological inflammation and fibrosis. Regression occurs when the host's immune system attacks primary melanocytic tumour cells via tumour-infiltrating lymphocytes, resulting in fibrosis. The immunological mechanisms driving complete, partial and segmental regression may vary. In this first part of this two-part review, we review the history, histological criteria and pathogenesis of regression in primary cutaneous melanoma, while in Part 2 we will review the effect of histological regression on prognosis, evaluation and management.

1325P - Validation of a clinicopathological and gene expression profile (CP-GEP) model for sentinel lymph node metastasis in primary cutaneous melanoma

BackgroundAs primary cutaneous melanoma patients with a positive sentinel lymph node (SLN, stage III) are now considered candidates for adjuvant systemic therapy, a SLN biopsy (SLNB) is indicated in more patients. However, SLNB is an invasive procedure and is negative in approximately 80% of patients. Therefore, there is a need for a non-invasive test to accurately identify patients with primary cutaneous melanoma without nodal metastases. Here we describe the first independent validation of a recently developed CP-GEP model to predict nodal metastasis. This risk model combines Breslow thickness, age, and gene expression variables from the primary melanoma. MethodsThis study focused on all patients >18 years who underwent a SLNB at the Erasmus Medical Center (between January 2007 and December 2017), within 90 days after diagnosis of primary cutaneous melanoma. Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) primary cutaneous melanomas, reversed transcribed into cDNA and subsequently analyzed for the expression of 8 target genes involved in melanoma metastasis (ITGB3, PLAT, SERPINE2, GDF15, TGFBR1, LOXL4, IL8, MLANA) using an optimized qPCR protocol. ResultsFFPE tissue samples from 211 patients were analyzed using the CP-GEP model. At diagnosis, the median age was 55 years (interquartile range [IQR] 45-65), and the median Breslow thickness was 2.1mm (IQR 1.4-3.4). Most patients presented with a T2 or T3 melanoma, accounting for 94 and 70 patients, respectively. Overall, 27.5% of patients had a positive SLN. The CP-GEP model had a negative predictive value (NPV) of 89.4%. In patients with stage T1-T2 melanoma, the model was able to achieve an SLNB reduction rate of 40.1% with an NPV of 90.7%. ConclusionsThe CP-GEP model is a non-invasive and validated tool that is able to predict nodal metastasis in an independent Dutch population. Consequently, this risk model is able to accurately identify patients with primary cutaneous melanoma that can safely forego SLNB. Therefore, the CP-GEP model is a promising tool for patient care, preventing unnecessary surgery in the majority of patients. Legal entity responsible for the studyErasmus University Medical Center, Department of Dermatology. FundingSkylineDx. DisclosureJ.T. Dwarkasing: Shareholder / Stockholder / Stock options, Full / Part-time employment: SkylineDx BV. D. Tempel: Shareholder / Stockholder / Stock options, Full / Part-time employment: SkylineDx BV. L. Bosman: Shareholder / Stockholder / Stock options, Full / Part-time employment: SkylineDx. A.A.M. Van der Veldt: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Ipsen. All other authors have declared no conflicts of interest.

Histologic Features Associated With an Invasive Component in Lentigo Maligna Lesions

Lentigo maligna (LM) presents an invasive component in up to 20% of biopsied cases, but to date the histologic features useful in detecting this invasive component have not been described. Some histologic characteristics are hypothesized to contribute to the progression of LM invasion. To identify the histologic characteristics associated with lentigo maligna melanoma (LMM) in patients with LM diagnosed by a partial diagnostic biopsy. A retrospective cross-sectional study of patients treated between January 1, 2000, and December 31, 2017, was conducted in a referral oncology center in València, Spain. Data and specimens of patients (n = 96) with a diagnosis of primary cutaneous melanoma in the form of either LM or LMM who had undergone surgical treatment, a complete histologic examination of the whole tumor, and an initial diagnostic partial biopsy of LM were included in the study. Histologic assessment was blinded to the presence of an invasive component. All biopsy specimens were evaluated for the presence of certain histologic characteristics. Comparisons between invasive samples and samples without an invasive component were performed. The differences in the distribution of variables between the groups were assessed using the χ2 and Fisher exact tests, and the degree of association of the relevant variables was quantified by logistic regression models. A classification and regression tree analysis was performed to rank the variables by importance. In total, 96 patients had sufficient histologic material that could be evaluated. The patients were predominantly male (56 [58.3%]) and had a mean (SD) age at diagnosis of 72 (12) years. Of these patients, 63 (65.6%) had an LM diagnosis and 33 (34.4%) had an LMM diagnosis (an invasive component). The histologic variables associated with the presence of an invasive component were melanocytes forming rows (odds ratio [OR], 11.5; 95% CI, 1.4-94.1; P = .02), subepidermal clefts (OR, 2.8; 95% CI, 1.0-7.9; P = .049), nests (OR, 3.0; 95% CI, 1.1-8.6; P = .04), and a lesser degree of solar elastosis (OR, 0.4; 95% CI, 0.1-1.1; P = .07). A classification and regression tree analysis of the relevant histologic features was able to accurately identify lentigo maligna with an invasive component (LMM) in more than 60% of patients. These findings may be useful in classifying early LM specimens at higher risk of invasion, which may eventually be relevant in identifying the most appropriate management for LM.

METASTATIC TUMOR OF THE HEART PRESENTED AS PRIMARY MYOCARDIAL INFARCTION IN A YOUNGER WOMAN

Metastatic tumours requires further investigation in the cardio-oncology field as they are extremely rare and have a large variety of clinical signs and symptoms, complicating the diagnostic process. Wepresent a clinical case of the delayed diagnosis of primary cutaneous melanoma after cardiovascular complications have developed (myocardial infarction and recurrent paroxysmal heart rhythm disturbances). The complications were caused by the tumor invasion into the left ventricular myocardium.

Follow-Up Recommendations after Diagnosis of Primary Cutaneous Melanoma: A Population-Based Study in New South Wales, Australia.

Follow-up practices after diagnosis and treatment of primary cutaneous melanoma vary considerably. We aimed to determine factors associated with recommendations for follow-up setting, frequency, skin surveillance, and concordance with clinical guidelines. The population-based Melanoma Patterns of Care study documented clinicians' recommendations for follow-up for 2148 patients diagnosed with primary cutaneous melanoma over a 12-month period (2006/2007) in New South Wales, Australia. Multivariate log binomial regression models adjusted for patient and lesion characteristics were used to examine factors associated with follow-up practices. Of 2158 melanomas, Breslow thickness was<1mm for 57% and≥1mm for 30%, while in situ melanomas accounted for 13%. Follow-up was recommended for 2063 patients (96%). On multivariate analysis, factors associated with a recommendation for follow-up at a specialist center were Breslow thickness≥1mm [prevalence ratio (PR) 1.05, 95% confidence interval (CI) 1.01-1.09] and initial treatment at a specialist center (PR 1.12, 95% CI 1.08-1.16). Longer follow-up intervals of>3months were more likely to be recommended for females, less likely for people living in rural compared with urban areas, and less likely for thicker (≥1mm) melanomas compared with in situ melanomas. Skin self-examination was encouraged in 84% of consultations and was less likely to be recommended for patients≥70years (PR 0.88, 95% CI 0.84-0.93) and for those with thicker (≥1mm) melanomas (PR 0.92, 95% CI 0.86-0.99). Only 1% of patients were referred for psychological care. Follow-up recommendations were generally consistent with Australian national guidelines for management of melanoma, however some variations could be targeted to improve patient outcomes.

Differences in the diagnosis of primary cutaneous melanoma in the public and private healthcare systems in Joinville, Santa Catarina State, Brazil

Background:Cutaneous melanoma accounts for up to 80% of deaths caused by skin cancer. Diagnostic suspicion and access to medical care and early intervention in suspected cases is vital to the patient’s prognosis. Objectives:To compare demographic and histopathological characteristics of primary cutaneous melanoma diagnosed in the public healthcare system (Sistema Único de Saúde SUS) and the private system in Joinville, Santa Catarina State, Brazil. Methods:This cross-sectional retrospective study analyzed primary cutaneous melanoma cases recorded from 2003 to 2014 in the resident population of Joinville. Ethical approval was obtained from the local Research Ethics Committee. Results:893 cases of primary cutaneous melanoma were identified. Patients in the private system were mostly younger, while there were more elderly patients in the public healthcare system (p <0.001). There was no statistically significant association between type of care (public/private) and gender or presence of multiple primary cutaneous melanomas. Histological diagnosis of superficial spreading melanoma was more common in patients treated in private healthcare, while nodular melanoma was more frequent in patients in the public healthcare system (p <0.001). Mean Breslow depth in patients treated in private healthcare was 1.35mm, compared to 2.72mm in the public system (p <0.001). Study limitations:This was a retrospective study using secondary databases. Conclusions:thin cutaneous melanoma (in situ cutaneous melanoma and Breslow T1) showed the strongest association with the private healthcare system, while thick cutaneous melanoma was more frequent in the public system (Breslow category T3 and T4) (p <0.001).

Genetic counselling and high-penetrance susceptibility gene analysis reveal the novel CDKN2A p.D84V (c.251A>T) mutation in melanoma-prone families from Italy.

Genetic susceptibility to primary cutaneous melanoma (PCM) may account for up to 12% of PCMs, presenting as the familial atypical mole/multiple melanoma syndrome (FAMMM), an autosomal dominant condition with incomplete penetrance and variable expressivity, characterized by PCM in at least two relatives and/or more than one PCMs in the same patient. To identify individuals at high genetic risk of PCM, from 1 January 2012 to 31 December 2015, we offered genetic counselling and molecular analysis of the two high-penetrance FAMMM susceptibility genes, cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase 4 (CDK4), to 92 consecutive, unrelated patients with FAMMM. Age at diagnosis and number of PCMs were obtained from medical records; the number of PCMs and affected relatives were recorded for each family. The diagnostic work-up consisted of genetic counselling and cascade genetic testing in patients and further extension to relatives of those identified as mutation carriers. All exons and exon/intron boundaries of CDKN2A and CDK4 genes were screened by direct bidirectional sequencing. We identified CDKN2A mutations in 19 of the 92 unrelated patients (20.6%) and in 14 additional, clinically healthy relatives. Eleven of these latter subsequently underwent excision of dysplastic nevi, but none developed PCM during a median follow-up of 37.3 months. In three patients from unrelated families, the novel CDKN2A p.D84V (c.251A>T) mutation was observed, associated with PCM in each pedigree. Genetic screening of FAMMM patients and their relatives can contribute towards specific primary and secondary prevention programmes for individuals at high genetic risk of PCM. The novel CDKN2A p.D84V (c.251A>T) mutation adds to the known mutations associated with FAMMM.

Pediatric melanomas often mimic benign skin lesions: A retrospective study

Childhood melanoma can be misdiagnosed because of its rarity and atypical presentation. We sought to correlate the clinical appearance of pediatric melanomas with Breslow depth and clinical behavior, and to identify diagnostic errors made by dermatologists and nondermatologist physicians. This was a retrospective review of Mayo Clinic records of children and young adults 21years of age or younger with a diagnosis of primary cutaneous melanoma between January 2000 and January 2015. Pediatric melanomas that mimicked benign skin lesions were more often deeper (>1mm; odds ratio 5.48; P=.002) and had a higher T stage (odds ratio [T2, T3, or T4] 6.28; P=.001) than melanomas with a clinically malignant appearance. Of pediatric melanomas, 66% originally diagnosed as benign melanocytic lesions exhibited changes in size, shape, and color. Sample size and retrospective design are limitations. Benign-appearing pediatric skin lesions with a history of evolution, bleeding, or ulceration should raise suspicion for melanoma. Melanomas demonstrating these features are associated with a higher Breslow depth and T stage. Although biopsy of all lesions that exhibit change in children is not practical, safe, or desired, close monitoring is recommended.

BRAF and epithelial-mesenchymal transition in primary cutaneous melanoma: a role for Snail and E-cadherin?

In vitro studies in melanoma indicate that up-regulation of the transcriptional repressor Snail occurs with a concomitant decrease of its target E-cadherin, both hallmarks of epithelial-mesenchymal transition-an association not established in vivo. We sought to elucidate the relationship between BRAF, Snail, E-cadherin, and established histopathologic prognosticators in primary cutaneous melanoma. Archived annotated samples with a diagnosis of primary cutaneous melanoma were retrieved (n = 68 cases; 34 BRAF mutant and 34 BRAF wild type) and immunohistochemically stained for Snail and E-cadherin protein expression. A semiquantitative scoring system was used. Multivariate logistic analysis was used to control confounders of BRAF. Snail expression was significantly associated only with ulceration (42% versus 13%; P = .02). E-cadherin expression was present in 26% of BRAF mutant and 71% of BRAF wild-type cases (P = .0003). Loss of E-cadherin expression was associated with female sex (60% versus 34%; P = .05), BRAF mutation (74% versus 29%; P = .0003), thickness greater than or equal to 1 mm (68% versus 32%; P = .004), mitosis (63% versus 25%; P = .007), and ulceration (75% versus 44%; P = .05). BRAF mutation was associated with male sex (60% versus 30%; P = .02), Breslow thickness (P = .007), thickness greater than or equal to 1 mm (68% versus 29%; P = .002), and ulceration (75% versus 42%; P = .02). Snail expression did not correlate with loss of E-cadherin expression (47% versus 53%; P = .79). After controlling for potential confounding, BRAF mutation was associated with loss of E-cadherin (adjusted odds ratio, 8.332; 95% confidence interval, 2.257-30.757; P = .0015) and Breslow thickness greater than 1 mm (adjusted odds ratio, 7.360; 95% confidence interval, 1.534-35.318; P = .0126). Our findings, indicating that mutant BRAF represses E-cadherin expression, implicating a catalytic role for BRAF in epithelial-mesenchymal transition.

Guidelines of the Brazilian Dermatology Society for diagnosis, treatment and follow up of primary cutaneous melanoma--Part I.

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In the first part, the following clinical questions were answered: 1) The use of dermoscopy for diagnosis of primary cutaneous melanoma brings benefits for patients when compared with clinical examination? 2) Does dermoscopy favor diagnosis of nail apparatus melanoma? 3) Is there a prognostic difference when incisional or excisional biopsies are used? 4) Does revision by a pathologist trained in melanoma contribute to diagnosis and treatment of primary cutaneous melanoma? What margins should be used to treat lentigo maligna melanoma and melanoma in situ?

Presumed melanoma-associated retinopathy (MAR): a presenting sign of primary small intestinal melanoma?

Melanoma-associated retinopathy is a paraneoplastic retinopathy associated mostly with cutaneous melanoma. In most cases it presents months to years after diagnosis of primary cutaneous melanoma was made or after recurrence. We describe a 55-year-old male patient who presented with symptoms of decreased vision and photopsia. Diagnosis of melanoma-associated retinopathy was made, but no primary cutaneous melanoma was found. 3 months later he developed intestinal perforation due to small intestinal melanoma.

The Impact of Shave Biopsy on The Management of Patients with Thin Melanomas

Disagreement persists regarding the role that various biopsy methods should play in the diagnosis of primary cutaneous melanoma. We analyzed the indications for sentinel lymph node (SLN) biopsy and the rates of SLN involvement among biopsy techniques and deep margin status to attempt to determine impact of shave biopsy on surgical management of patients with thin melanoma. All patients who underwent SLN biopsy for melanoma with Breslow thickness less than 1 mm between 1998 and 2006 were identified. Patient and tumor characteristics were compared using χ(2) tests for categorical variables. Continuous variables were reported as a mean ± standard deviation and analyzed using t test. Of the 260 patients diagnosed with thin melanomas, 159 (61.2%) were diagnosed by shave biopsy; 101 (38.8%) were diagnosed by other techniques. Of the 159 patients diagnosed by shave biopsy, 18.2 per cent (n = 29) underwent SLN biopsy with the only indication being positive deep margin. The frequency of SLN positivity did not differ between the biopsy groups (3.1% vs 4.0%, P = 0.726) or between groups that had positive or negative deep margins (3.0% vs 3.3%, P = 0.839, respectively). For patients unable to undergo general anesthesia, the increased rate of performing SLN biopsy resulting from shave biopsy should limit its use in these patients. However, shave biopsy is a reasonable diagnostic method for patients at low risk for general anesthesia, particularly because it results in comparably low rates of positive SLN. Thus each patient's unique clinical situation should be considered when deciding which biopsy technique is appropriate.

Histopathological characterization of primary cutaneous melanoma using infrared microimaging: a proof-of-concept study

The diagnosis of malignant melanoma is based upon the histological evaluation of the lesion. As such, the morphological interpretation relies on the expertise of a dermatopathologist. Infrared microimaging is emerging as a new powerful tool to investigate tissue biochemistry. Infrared spectra probe the biochemical constitution of the sample and are real tissue-specific spectroscopic fingerprints. To assess the potential of infrared microimaging to aid in the analysis of tissue sections from primary cutaneous melanomas. Ten samples of melanoma sections from the main histological subtypes were investigated using infrared microimaging combined with multivariate statistical analyses. This methodology yielded highly contrasted colour-coded images that permitted to highlight tissue architecture without any staining. It was possible to discriminate tumour areas from normal epidermis automatically, and intratumoral heterogeneity as revealed by our approach was correlated with the aggressiveness of the tumour. This proof-of-concept study shows that infrared microimaging could help in the diagnosis of primary cutaneous melanoma.

Cutaneous melanoma: baseline and ongoing laboratory evaluation

Numerous laboratory tests and imaging methods are available that can be used in patients who are diagnosed with cutaneous melanoma. The downside risks related to testing are cost and patient anxiety. Therefore, it must be critically considered which examinations are useful and feasible. After a diagnosis of primary cutaneous melanoma, many physicians in Germany perform lymph node ultrasound to detect occult regional metastasis. Whole-body imaging techniques, except the physical examination, are unlikely to detect distant occult metastasis. In tumors that have an intermediate or high risk of recurrence (> 1 mm tumor thickness), baseline whole-body imaging may serve as a reference for ongoing evaluation. During follow-up care, physical examination alone is appropriate when there is a low risk for recurrence (up to 1-mm tumor thickness). In patients whose tumors are > 1 mm thickness, regular lymph node ultrasound examinations and determination of serum tumor marker S-100beta protein are commonly used by physicians in Germany. Whole-body imaging techniques are useful in patients who have locoregional and/or distant metastasis. For consideration of surgical resections in stage IV disease, more advanced examinations techniques such as positron emission tomography-computed tomography or whole body magnetic resonance imaging may be used. Early detection of limited disease using these methods may be helpful for patients who have locoregional metastases and for 10-20% of patients who have distant metastases and whose limited disease may be amenable to surgical resection.

New techniques in the diagnosis of primary cutaneous melanoma

New techniques in the diagnosis of primary cutaneous melanoma

Diverse expansion potential and heterogeneous avidity in tumor-associated antigen-specific T lymphocytes from primary melanoma patients

While tumor-associated antigen (TAA)-specific CD8(+) T lymphocytes have been detected in metastatic melanoma patients, immune response in early disease phases has not yet been carefully evaluated. We looked for circulating cytotoxic T lymphocytes (CTL) directed against Melan-A / MART1, tyrosinase, gp100 and MAGE-3 antigens in patients with a diagnosis of primary cutaneous melanoma by using fluorescent HLA-A2 tetramers. In five out of six cases high numbers of CD8(+)/tetramer(+) cells could be detected by flow cytometry, and in four patients lymphocyte populations specific for two different melanoma antigens (Melan-A/MART1 and tyrosinase) were contemporaneously present. The TAA-specific cells could represent as much as 1/220 T lymphocytes in the circulating CD8(+) population. When tetramers were used to monitor the in vitro expansion of TAA-specific CTL precursors upon antigen-specific stimulation, a diverse expansion potential was evidenced in CTL from the different donors and, more strikingly, in CTL specific for the different TAA. Melan-A/MART1-specific CTL clones derived from two patients exhibited a broad range of avidity. Only the highest avidity clones, representing about 50 % of the cases analyzed, were tumor specific. By correlating tetramer staining with clone avidity, we found that tetramer fluorescence intensity could represent a good indicator of TCR affinity, but not of overall clone avidity.

Expression of Melan-A/MART-1 antigen as a prognostic factor in primary cutaneous melanoma.

In this study we assessed the expression of the Melan-A/MART-1 antigen by immunohistochemistry using monoclonal antibody A103 in 73 primary cutaneous melanomas and its correlation with tumor staging and patient survival. Melan-A/MART-1 was expressed in 90% of primary tumors, with loss of expression increasing with Breslow thickness. Kaplan-Meier analysis demonstrated a significantly reduced disease-free interval and overall survival rate for patients not expressing this antigen. The poor prognosis of such patients was even worse for those presenting with a primary melanoma and a Breslow thickness of > or = 1 mm. Thus, Melan-A/MART-1 is not only a useful and specific additional marker for the diagnosis of primary cutaneous melanoma, but it may also help refine the prognosis of patients with malignant melanoma.