Cutaneous Melanoma Metastases Research Articles

BRAF Mutation Status Concordance Between Primary Cutaneous Melanomas and Corresponding Metastases: A Review of the Latest Evidence

The identification of B-Raf proto-oncongene (BRAF) mutation and the emergence of targeted therapy marked a turning point in the treatment of melanoma. The study of mutation status concordance between primary tumors and metastases in this cancer has major treatment implications as it facilitates the selection of candidates for targeted therapy. This review analyzes the evidence on the level of mutation status concordance between primary tumors and different types of metastases in cutaneous melanoma and provides an overview of the advantages and disadvantages of the various methods used to detect BRAF mutations.

Concordancia mutacional de BRAF entre melanoma primario cutáneo y sus correspondientes metástasis. Revisión de la evidencia actual

The identification of B-Raf proto-oncongene (BRAF) mutation and the emergence of targeted therapy marked a turning point in the treatment of melanoma. The study of mutation status concordance between primary tumors and metastases in this cancer has major treatment implications as it facilitates the selection of candidates for targeted therapy. This review analyzes the evidence on the level of mutation status concordance between primary tumors and different types of metastases in cutaneous melanoma and provides an overview of the advantages and disadvantages of the various methods used to detect BRAF mutations.

Abstract 477: Down-regulated miR-23a contributes to invasion and metastasis of cutaneous melanoma by promoting autophagy

Abstract Background: The occurrence of invasion and metastasis is the major cause of mortality in melanoma. Recent studies suggest that dysregulated miRNAs play critical roles in this procedure, but the underlying mechanism remains elusive. Here, we show that down-regulated miR-23a can promote invasion-metastasis cascade through autophagy in melanoma.Methods: The role of miR-23a in prognosis was assessed in a cohort of melanoma patients (n = 192) with Kaplan-Meier analysis. The effects of miR-23a overexpression were investigated using assays of invasion, migration and in a xenograft model (n = 10 mice per group). Autophagy-related target of miR-23a was confirmed by bioinformatics analysis, luciferase assays and immunoblotting. Molecular studies were performed to determine the downstream cellular and molecular mechanisms. All statistical tests were two-sided.Results: Serum miR-23a level was significantly down-regulated in melanoma patients (P< .001) and was highly correlated with poor clinical outcomes (P = .027, log-rank test). In addition, miR-23a level was remarkably decreased in metastatic melanoma tissues and cell lines (P<.05, P<.01). Moreover, miR-23a overexpression prevented the invasion and migration in vitro and lung and liver metastasis in vivo (both P< .05), by targeting ATG12 and inhibiting autophagy. Mechanically, miR-23a-ATG12 axis attenuated invasion and migration through autophagy-mediated AMPK-RhoA pathway. Finally, the down-regulation of miR-23a in metastatic melanoma was caused by RUNX2 in a transcriptional repression-manner. Conclusion: MiR-23a can act as a crucial epigenetic repressor of melanoma invasion and metastasis in an autophagy-dependent way, which indicates that miR-23a-mediated autophagy inhibition can be exploited to restrain invasion-metastasis cascade in melanoma treatment. Note: This abstract was not presented at the meeting. Citation Format: Weinan Guo, Huina Wang, Yuqi Yang, Sen Guo, Weigang Zhang, Tao Zhao, Lin Liu, Zhe Jian, Ling Liu, Gang Wang, Tianwen Gao, Qiong Shi, Chunying Li. Down-regulated miR-23a contributes to invasion and metastasis of cutaneous melanoma by promoting autophagy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 477. doi:10.1158/1538-7445.AM2017-477

Lymphatic invasion predicts sentinel lymph node metastasis and adverse outcome in primary cutaneous melanoma.

Sentinel lymph node (SLN) metastasis is a powerful predictor of survival in primary cutaneous melanoma. Lymphatic invasion (LI) may correlate with increased risk of SLN metastasis. Intralymphatic metastases, often difficult to detect on hematoxylin and eosin (H&E) stained sections, are readily identified with dual immunohistochemistry for melanocytic and lymphatic markers. We used dual S100/D240 immunohistochemistry to detect LI in 125 melanomas from patients who underwent SLN biopsy and correlated LI with melanoma staging parameters and disease status. Dual immunohistochemistry allowed for the identification of LI in 33 cases (26%), compared to only 2% on H&E stained sections. Melanomas with LI showed greater thickness, higher mitotic rate and more frequent ulceration. Eleven of 33 cases with LI (33%) and 10 of 92 cases without LI (11%) were associated with a positive SLN (P = .006). More patients without LI were disease-free at last follow-up (80%) than patients with LI (50%; P = .002); LI was significantly associated with decreased progression-free survival. The detection of LI is improved by dual immunohistochemistry and predicts SLN metastasis. The presence of LI may impact therapeutic planning in melanoma, such as the decision to perform a SLN biopsy.

Lymphatic invasion and the Shields index in predicting melanoma metastases

Findings of the prognostic significance of lymphatic invasion are contradictory. To determine an as efficient cutaneous melanoma metastasis predictor as possible, Shields etal. created a new prognostic index. This study aimed to examine whether the lymphatic invasion analysis and the Shields index calculation can be used in predicting lymph node status in patients with cutaneous melanoma. Lymphatic invasion of 100 melanoma specimens was detected by dual immunohistochemistry staining for the lymphatic endothelial marker D2-40 and melanoma cell S-100 protein. The Shields index was calculated as a logarithm by multiplying the melanoma thickness, square of peritumoural lymphatic vessel density and the number "2" for the present lymphatic invasion. No statistically significant difference was observed between lymph node metastatic and nonmetastatic melanomas regarding the lymphatic invasion. Metastatic melanomas showed a significantly higher Shields index value than nonmetastatic melanomas (p=0.00). Area under the receiver operator characteristic (ROC) curve (AUC) proved that the Shields index (AUC=0.86, 95% confidence interval (CI) 0.79-0.93, p=0.00) was the most accurate predictor of lymph node status, followed by the melanoma thickness (AUC=0.76, 95% CI 0.67-0.86, p=0.00) and American Joint Committee on Cancer (AJCC) staging (AUC=0.75, 95% CI 0.66-0.85, p=0.00), while lymphatic invasion was not successful in predicting (AUC=0.56, 95% CI 0.45-0.67, p=0.31). The Shields index achieved 81.3% sensitivity and 75% specificity (cut-off mean value). Our findings show that D2-40/S-100 immunohistochemical analysis of lymphatic invasion cannot be used for predicting the lymph node status, while the Shields index calculation predicts disease outcome more accurately than the melanoma thickness and AJCC staging.

Parallel profiling of immune infiltrate subsets in uveal melanoma versus cutaneous melanoma unveils similarities and differences: A pilot study

ABSTRACT The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8+ T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.

Effect of gene expression profile (GEP) testing on clinical management in 19% of consecutively treated patients with stage IB/IIA melanoma at a single institution.

e21080 Background: A 31-GEP test is predictive of metastasis in cutaneous melanoma. We hypothesized that GEP testing would “upgrade” surveillance to routine imaging in at least 16% of stage IB/IIA patients, similar to the upgrade rate from sentinel node biopsy. Methods: A GEP score was obtained for consecutive patients with Stage IB/IIA melanoma treated between 6/2014-6/2016. A retrospective review of a prospectively collected database was performed. Results: 67 patients with Stage IB/IIA melanoma met inclusion criteria. In four cases, a GEP result was not available. Of the 63 tested cases, 68% were Stage IB (N = 43), and 32% were Stage IIA (N = 20). A high-risk result was seen in 12% of stage IB (5/43) and 42% of stage IIA (8/19) patients. Insurance denied coverage of scans in 1/13 patients with a high-risk GEP result. The remaining 12 Stage IB/IIA patients with high-risk scores were “upgraded” to high-intensity surveillance. With a median follow-up of 14 months, 1/13 patients with a high-risk GEP result developed distant metastases 21 months after diagnosis of a Stage IIA melanoma. Conclusions: Results from this retrospective single institution study show that GEP testing altered patient management in 19% of Stage IB/IIA patients. Early detection in 1/13 patients with high-risk scores in this series supports further investigation into stratifying traditionally low-risk patients by GEP testing.

Interim analysis of survival outcomes in a prospective cohort evaluating a prognostic 31-gene expression profile (GEP) test for melanoma.

9573 Background: DecisionDx-Melanoma has been validated as an accurate prognosticator of cutaneous melanoma (CM) metastasis risk. The GEP test classifies CM pts as Class 1 (low risk) or Class 2 (high risk). Interim survival analysis from two clinical registry studies (NCT02355574/NCT02355587) designed to prospectively evaluate outcomes in pts for whom the GEP test was performed is described. Methods: Eleven US dermatologic and surgical centers participated in the IRB-approved protocols. Physicians enrolled CM pts who were ≥16 years old and had successful GEP test results. Endpoints of recurrence-free (RFS), distant metastasis-free (DMFS) and melanoma-specific survival (MSS) were assessed using Kaplan-Meier and Cox regression analysis. As an interim analysis at year 3 of an expected 5-year study, the critical alpha level (p-value) was 0.01. Results: At the time of data extraction, 322 pts were accrued and completed at least one follow-up visit. Median age was 58 years (range 18-87), median Breslow thickness (BT) was 1.2mm, 55% were male, 20% (58/296) were ulcerated, and 15% (36/237 biopsied) had a positive sentinel lymph node (SLN). Median follow-up time was 1.5 years for pts without a recurrence. Of 25 recurrent cases, 80% (20/25) were Class 2 and 40% (10/25) were SLN-positive. Two percent of Class 1 pts had a recurrence compared to 6% (12/201 biopsied) of SLN-negative pts. Of the SLN-negative pts who recurred, 75% (9/12) were called Class 2. Combined GEP and SLN risk prediction identified 88% (21/24) of recurrences. Kaplan-Meier event rates for each class are shown in the table. In Cox multivariate analysis, BT and GEP Class 2 were significant predictors of recurrence (p<0.01 for each). Conclusions: Results of this analysis show that the GEP test provides prognostic information that complements conventional staging and significantly enhances identification of high risk CM pts, consistent with reported validation studies.The results support use of the test for guiding surveillance decisions and enrollment of CM pts in clinical trials. Clinical trial information: NCT02355574, NCT02355587. [Table: see text]

Multi-elemental imaging of paraffin-embedded human samples by laser-induced breakdown spectroscopy

Chemical elements play central roles for physiological homeostasis in human cells, and their dysregulation might lead to a certain number of pathologies. Novel imaging techniques that improve the work of pathologists for tissue analysis and diagnostics are continuously sought. We report the use of Laser-Induced Breakdown Spectroscopy (LIBS) to perform multi-elemental images of human paraffin-embedded skin samples on the entire biopsy scale in a complementary and compatible way with microscope histopathological examination. A specific instrumental configuration is proposed in order to detect most of the elements of medical interest (i.e. P, Al, Mg, Na, Zn, Si, Fe, and Cu). As an example of medical application, we selected and analysed skin biopsies, including healthy skin tissue, cutaneous metastasis of melanoma, Merkel-cell carcinoma and squamous cell carcinoma. Clear distinctions in the distribution of chemical elements are observed from the different samples investigated. This study demonstrates the high complementarity of LIBS elemental imaging with conventional histopathology, opening new opportunities for any medical application involving metals.

589 Mechanisms of antitumor immunity by intralesional Mycobacterium bovis Bacillus Calmette-Guerin (BCG) in cutaneous melanoma metastases

589 Mechanisms of antitumor immunity by intralesional Mycobacterium bovis Bacillus Calmette-Guerin (BCG) in cutaneous melanoma metastases

Transdermal Gene Delivery by Functional Peptide-Conjugated Cationic Gold Nanoparticle Reverses the Progression and Metastasis of Cutaneous Melanoma.

Permeability barrier imposed by stratum corneum makes an extreme challenge for the topical delivery of plasmid DNA (pDNA), which is widely used in gene therapy. Existing techniques to overcome the skin barrier for bio-macromolecules delivery rely on sophisticated mechanical devices. It is still a big challenge to treat the skin cancer, for example, melanoma, that initiates in the dermal layer by topical gene therapy. To facilitate the skin penetration of pDNA deeply into the melanoma tissues, we here present a cell-penetrating peptide and cationic poly(ethyleneimine) conjugated gold nanoparticle (AuPT) that can compact the pDNAs into cationic nanocomplexes and penetrate through the intact stratum corneum without any additional enhancement used. Moreover, the AuPT is highly efficient in stimulating the intracellular uptake and nuclear targeting of the pDNAs in cells, which guarantees the effective transfection. This study provides evidence that penetrating peptide conjugated cationic gold nanoparticle offers a promising vehicle for both the skin penetration and transfection of pDNAs, possessing great potential in topical gene therapy.

The Impact of Smoking on Sentinel Node Metastasis of Primary Cutaneous Melanoma.

Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy. Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis. Current smoking was strongly associated with SLN metastasis (p=0.004), even after adjusting for other predictors of metastasis. Among 4231 patients (1025 in MSLT-I and 3206 in MSLT-II), current or former smoking was also independently associated with ulceration (p<0.001 and p<0.001, respectively). Compared with current smoking, never smoking was independently associated with decreased Breslow thickness in multivariate analysis (p=0.002) and with a 0.25mm predicted decrease in thickness. The direct correlation between current smoking and SLN metastasis of primary cutaneous melanoma was independent of its correlation with tumor thickness and ulceration. Smoking cessation should be strongly encouraged among patients with or at risk for melanoma.

Ileoileal intussusception caused by the metastasis of cutaneous malignant melanoma to the small bowel 6 years after its excision presenting with small bowel obstruction.

Ileoileal intussusception caused by the metastasis of cutaneous malignant melanoma to the small bowel 6 years after its excision presenting with small bowel obstruction.

Down-regulated miR-23a Contributes to the Metastasis of Cutaneous Melanoma by Promoting Autophagy.

Melanoma is among the most aggressive tumors, and the occurrence of metastasis leads to a precipitous drop in the patients' survival. Therefore, identification of metastasis-associated biomarkers and therapeutic targets will contribute a lot to improving melanoma theranostics. Recently, microRNAs (miRNAs) have been implicated in modulating cancer invasion and metastasis, and are proved as potential non-invasive biomarkers in sera for various tumors. Here, we reported miR-23a as a novel metastasis-associated miRNA that played a remarkable role in modulating melanoma invasive and metastatic capacity and was of great value in predicting melanoma metastasis and prognosis. We found that serum miR-23a level was significantly down-regulated in metastatic melanoma patients and highly correlated with poor clinical outcomes. In addition, miR-23a level was also remarkably decreased in metastatic melanoma tissues and cell lines. Furthermore, overexpressed miR-23a suppressed the invasive and migratory property of melanoma cells by abrogating autophagy through directly targeting ATG12. Specially, miR-23a-ATG12 axis attenuated melanoma invasion and migration through autophagy-mediated AMPK-RhoA pathway. Finally, the overexpression of miR-23a prevented melanoma metastasis in vivo. Taken together, our findings demonstrate that the metastasis-associated miR-23a is not only a potential biomarker, but also a valuable therapeutic target for melanoma.

Recidiva tardia de melanoma cutâneo: relato de caso

Introduction: Ten-year survival for patients with cutaneous malignant melanoma (CMM) is considered to be synonymous with cure. However, there are reports of late recurrence after this period. This report stresses the importance of awareness of late recurrences and reflects on the role of the family physician (FP) in timely diagnosis. Case description: A 50-year-old man, who was a smoker with history of arterial hypertension and the excision of a CMM at 28 years of age, came to see his FP complaining of a dry cough for two days. An upper respiratory tract infection was diagnosed and treated symptomatically. One month later he returned due to the persistence of the cough. There were no other abnormal signs or symptoms. The cough was presumed to be a side effect of Zofenopril prescribed for control of arterial hypertension. This was stopped and replaced with Irbesartan. He returned two months later with the same complaint. There were no complaints of fever, sweating, chest pain, haemoptysis, or weight loss. Physical examination was normal. The erythrocyte sedimentation rate, ordered by his occupational health doctor, was 87mm/h. The diagnoses of pulmonary tuberculosis or lung cancer were considered. He was referred to the local emergency room, where a thoracic computerized tomography scan was performed. It revealed a proliferative nodular lesion on the left lung apex, compatible with lung cancer. The patient was referred for a pulmonary consultation, and was then admitted to hospital for partial resection of the mass. The histological results showed a metastasis of CMM, 22 years after the initial diagnosis. Comment: There are a growing number of reports of late recurrences of CMM. Early detection should be a concern for physicians. The FP can play an important role on monitoring these cases given the longitudinal continuity of care they provide.

Abstract 4897: First evidence of changes in the TCRâ repertoire from a cutaneous melanoma patient immunized with the CSF-470 vaccine

Abstract Introduction: A breakthrough of immunotherapy for cancer treatment has emerged, with promising results in several tumors. We have developed the allogeneic vaccine CSF-470, composed of lethally-irradiated human Cutaneous Melanoma (CM) cell lines plus BCG and GM-CSF, currently tested in a Phase II-III study in adjuvancy (NCT01729663). The aim of this work was to analyze the TCRâ repertoire in multiples samples obtained through CSF-470 vaccination from a CM patient who developed a cutaneous metastasis (Mts) at the end of the 2-year immunization protocol. Methods: DNA from PBMC at 0, 12 and 24 months (PRE-PBMC, POST-1, POST-3) from protocol start, and from Mts-TIL (Tumor Infiltrating Lymphocytes) was obtained. TCRâ sequence and further analysis was performed with the IMMUNOSEQ platform. Patterns were defined for clone tracking: 1, present at PRE, increases during immunization; 2, absent at PRE, increases during immunization; 3, present at PRE, absent following immunization; 4, present at PRE, decreases during immunization; 5, detected only at 24 months (POST-3); 6, absent at PBMC, present in Mts-TIL. Results: PBMC TCRâ repertoire analysis revealed an increase in clonality (2.3X) and total frequency of TOP100 clones through CSF-470 immunization. PBMC clones tracking analysis (with frequency ≥0.01%) revealed prevalence of Pattern-1 clones (54%) and Pattern-5 clones (30%). Regarding Mts-TIL, clones were distributed in Pattern-1 (23%), Pattern-3 (5%), Pattern-5 (16%), and Pattern-6 (53%). However, when analyzing TOP100 Mts-TIL clones, 60% of them corresponded to Pattern-1, 19% to Pattern-5 and only 12% to Pattern-6. Databases search revealed the presence in PBMC of shared TCRâ sequences previously reported in association to M.bovis infection. Also, some clones found in Mts-TILs matched to previously identified in other CM metastases. Conclusions: This is the first report of the TCRâ repertoire from a CM patient immunized with CSF-470 vaccine. The main observations regarding TCRâ repertoire analysis were: 1- Vaccination induced expansion of selected pre-immunization TCR clones, which might recognize dominant Ags either from patient′s tumor or vaccine. 2- TCR clones arising after immunization might recognize dominant Ags from vaccine or derived by epitope spreading from the patient′s tumor. 3- More than 50% of total clones were exclusively present in Mts-TIL, suggesting local activation. However, most frequent Mts-TIL clones included those that were expanded exclusively by CSF-470 vaccination. 4- TCRâ repertoire comparison also allowed detection of some clones already reported in TIL from CM Mts and in memory repertoire against M.Bovis, possibly accounting BCG adjuvancy. Finally, changes observed in the TCRâ repertoire from this patient, driven by the CSF-470 vaccine, suggest an anti-tumor immune response taking place both in the periphery and the local compartment. Citation Format: Mariana Aris, María Marcela Barrio, José Mordoh. First evidence of changes in the TCRâ repertoire from a cutaneous melanoma patient immunized with the CSF-470 vaccine. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4897.

Abstract CT021: Phase Ib study of a novel immunotherapy combination therapy of intralesional coxsackievirus A21 and systemic ipilimumab in patients with advanced melanoma

Abstract Background: CVA21 (CAVATAK) is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21. Intratumoral (i.t.) CVA21 injection can induce preferential tumor cell infection, tumor immune-cell infiltration, up-regulation of γ-INF response genes, cell lysis and enhancement of a systemic anti-tumor immune response. Pre-clinical studies in an immune-competent mouse model of melanoma have revealed that combinations of intralesional CVA21 and anti-CTLA-4 or anti-PD-1 mAbs mediated significantly greater antitumor activity and compared to use of either agent alone. Presented are the interim data of the open-label, multicenter Phase Ib MITCI (Melanoma Intra-Tumoral Cavatak and Ipilimumab) study of novel immunotherapy combination Coxsackievirus A21 and ipilimumab in patients with advanced melanoma Methods: The Phase Ib MITCI study (NCT02307149) is investigating the efficacy and safety of i.t. CVA21 and i.v. ipilimumab in 26 patients with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Pts received up to 3 × 10e8 TCID50 CVA21 i.t. on study days 1, 3, 5, 8 and 22, and then q3w for a further 6 series of injections. Ipilimumab (3 mg/kg) q3w was given as 4 i.v. infusions starting at Day 22. Treatment is continued until DLT, intolerance, all injectable tumors disappeared, or confirmed disease progression (PD) per immune-related (ir) WHO response criteria. The first response assessment occurs at study Day 106. Key eligibility criteria were ? 18 yrs old, ECOG PS 0-1, and at least 1 injectable cutaneous, subcutaneous, or nodal melanoma metastasis ? 1.0 cm. The primary endpoint was to assess safety of CAVATAK in combination with scheduled ipilimumab treatment. Secondary endpoints included irWHO objective response rate (ORR), responses in injected and non-injected lesions, durable response rate (continuous response ? 6 mos), median time to initial response, survival and QOL. Results: At present, of the 7 patients enrolled, no DLT's have been reported. Combination treatment has been generally well-tolerated with only 2 Gr 3 AEs reported, one with ipilimumab-related fatigue and the other with unrelated hypertension. Of 5 pts with investigator assessed response, ORR was 80%, with all responses occurring by 3.5 months and in both injected and non-injected lesions. Responses were observed in patients with Stage IIIC and Stage IV M1a/c disease. Response rates in individual injected and non-injected lesions were 80% (n = 10) and 87% (n = 15), respectively. Complete tumor responses were observed in some visceral and non-visceral lesions. Patients developed notable levels of anti-CVA21 serum neutralizing antibody by Day 22. Conclusions: Intralesional CVA21 + ipilimumab is a promising novel oncolytic immunotherapeutic combination for the treatment of unresectable Stage IIIC-IVM1c melanoma. At present no DLT has been achieved, with no Gr 3/4 CVA21-related AEs observed. The preliminary overall response rate (80%) is higher than published rates for either agent used alone (CVA21: 28.1% and ipilimumab:∼15-20%) in advanced melanoma patients. The combination immunotherapy treatment is generally well tolerated and has displayed antitumor activity in both local and systemic disease, also within environments of high levels of anti-CVA21 serum neutralizing antibody. Citation Format: Brendan Curti, Jon Richards, Mark Faries, Mark Grose, Roberta Karpathy, Darren R. Shafren. Phase Ib study of a novel immunotherapy combination therapy of intralesional coxsackievirus A21 and systemic ipilimumab in patients with advanced melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT021.

The role of microphthalmia transcription factor (Mitf) in prediction of distant metastases in cutaneous melanoma.

9564Background: Microphthalmia Transcription Factor (Mitf) plays a central role in melanocyte maturation and differentiation, as well as tumorigenesis. We previously proved that Mitf expression of ...

621 Down-regulated mir-23a contributes to invasion and metastasis of cutaneous melanoma by promoting autophagy

621 Down-regulated mir-23a contributes to invasion and metastasis of cutaneous melanoma by promoting autophagy

Expressions of STAT3 and phosphorylated STAT3 in cutaneous malignant melanoma lesions

Objective To investigate expressions of STAT3 and phosphorylated STAT3 (p-STAT3) in cutaneous malignant melanoma (CMM) lesions, and to explore their significance. Methods The expressions of STAT3 and p-STAT3 were detected with an immunohistochemical method using polymer enzyme-labeled secondary antibodies in skin specimens from 22 CMM lesions and 23 pigmented nevus lesions. The effects of STAT3 and p-STAT3 expressions on lymph node metastasis of CMM were evaluated. Results The expression rate of STAT3 was significantly higher in CMM lesions than in pigmented nevus lesions (95.5% vs. 56.5%, χ2 = 9.23, P 0.05), while the elevated expression of p-STAT3 in CMM lesions was a predictive factor for lymph node metastasis in CMM (OR = 1.88, 95% CI: 1.05 - 3.38, P< 0.05). Conclusion Increased expression of STAT3 and p-STAT3 in CMM may play important roles in the pathogenesis of CMM, and elevated p-STAT3 expression may contribute to invasion and metastasis of CMM. Key words: Melanoma; STAT3 transcription factor; Lymphatic metastasis; p-STAT3