Head And Neck Mucosal Melanoma Research Articles

KIT, NRAS and BRAF mutations in head and neck (upper aerodigestive tract) mucosal melanoma (a study of 21 cases)

Objective . Determination of mutation rates in KIT, NRAS and BRAF genes in 21 samples of mucosal melanoma of the upper aerodigеstive tract. Background. Head and neck mucosal melanomas (or upper aerodigestive tract mucosal melanomas) are rare and aggressive tumors of melanocytic origin. Head and neck mucosal melanoma (HNMM) comprises over 50 % of all mucosal melanomas. The aim was to determine the KIT, NRAS and BRAF mutation frequencies in 21 series of primary HNMM. Methods . Microdissected tumour cells were used from 21 formalin-fixed paraffin-embedded tumours. The tumour cells were screened for KIT, NRAS and BRAF mutations by direct sequencing. Results. Overall, 19 % (4 out of 21) of HNMMs harboured KIT, NRAS or BRAF mutations. Mutations in these oncogenes occurred in a mutuаlly exclusive manner. Both NRAS and BRAF mutations were identified at a similar frequency of 4,75 % each (1 and 1 out of 21), whereas KIT mutations were detected in 9,5 % (2 out of 21) of the HNMMs. KIT mutations were located in exon 11. Conclusion. Our findings shоw that NRAS and BRAF mutations, which are aсcessible for present targeted thеrapies, are only rarеly present in HNMMs, whereas KIT mutations seem to be relatively more frequent.

BRAF, NRAS, KIT, TERT, GNAQ/GNA11 mutation profile analysis of head and neck mucosal melanomas: a study of 42 cases

Head and neck mucosal melanoma (HNMuM), which occurs mostly in the sinonasal and oral cavity, constitutes less than 1% of all malignant melanomas. Treatment options fail to improve the prognosis of this aggressive tumour that has low overall survival rates. Thus, development of new targeted therapies is essential. Unfortunately, limited data exist regarding their molecular profile. BRAF, NRAS, KIT, TERT and GNAQ/GNA11 oncogene mutations were investigated in 42 HNMuMs (28 sinonasal, 13 oral, 1 nasopharyngeal). Mutation rates were as follows: BRAF (4.8%), NRAS (4.8%), KIT (9.5%), TERT (7.5%), GNAQ/GNA11 (0%). Among 11 cases that harboured mutations (26%), 10 (91%) were located in sinonasal and one (9%) in the oral cavity. The literature was reviewed with comparison of frequencies based on the gathered data. NRAS and TERT promoter mutation rates were significantly higher in sinonasal than in oral location (p<0.05). Our results indicated that BRAF, NRAS, KIT, TERT and GNAQ/GNA11 gene mutations occur at low frequencies in HNMuMs, and subgroups (oral versus sinonasal) differ in their molecular profile. Low rates of aforementioned mutations and activation of oncogenes by pathways other than sun exposure support the distinctive nature of HNMuMs with regard to their cutaneous counterparts.

A Study of C-MYC, SOX10 and BCL-2 Proteins Expression in Head and Neck Mucosal Melanomas

Background: Head and Neck Mucosal Melanoma (HNMM) is rare, accounting 1% of all melanomas in USA, and 6% in Japan. Melanoma’s development is a complex process involving activation of proto-oncogenes and loss of tumor suppressors. BCL-2 oncogene encodes a family of anti-apoptotic proteins and it is overexpressed in melanomas. On the other hand, proto-oncogene C-MYC is a transcriptional factor and plays crucial role both in driving cell proliferation and promoting apoptosis, its overexpression has been associated to melanoma progression. Moreover, oncogene SOX10 cooperates with other transcription factors to direct the development and differentiation of melanocytes. These three nuclear markers are associated to melanoma’s metastatic risk.Methods: We studied of BCL-2; C-MYC and SOX10 proteins in 19 Formalin Fixed Paraffin Embedded cases of HNMM from Yale School of Medicine and 10 cases from University of São Paulo by Alkalin Phosphatase immunohistochemistry technique.Results: We considered as positive expression when over 25% of tumor cells were immunostained. We observed 27/29 were positive to BCL-2 and 28/29 cases showed SOX10 expression (both markers showing immunostaining in over 75% of tumor cells). However, we noticed variable expression for C-MYC in 15/29 of HNMM cases.Conclusions: According to ours results, we suggest that BCL-2 and SOX10, should be good adjuctive biomarkers for HNMM, however lower expression of C-MYC has not shown to play main role in the HNMM development, thus further molecular biology studies should corroborate this present study.

Head and neck mucosal melanoma: clinicopathological analysis of 51 cases treated in a single cancer centre and review of the literature

Head and neck mucosal melanoma (HNMM) is a rare and aggressive malignancy. The objective of this study was to describe the outcomes of patients with HNMM. Clinical and pathological data from 51 patients with primary HNMM were reviewed. All patients were treated at a single cancer centre between 1954 and 2012. Most tumours involved the nasal cavity (35.3%) and upper gingiva (29.4%). The majority of lesions were ulcerated (54.9%) and pigmented (84.3%). Forty-three patients underwent surgical treatment and 21 (41.2%) underwent adjuvant chemotherapy and/or radiotherapy. Eight patients (15.7%) received palliative treatment. The median follow-up period was 21 months. During this period, 30 (58.8%) patients had tumour recurrences. At the last clinical evaluation, only seven (13.7%) patients were alive with no evidence of disease and three (5.9%) were alive with HNMM. There were significant differences in overall survival probability according to the presence of ulceration (P=0.004), metastatic lymph nodes (P=0.003), and treatment including a radical surgical procedure (P<0.001). On multivariate analysis, ulceration was the only variable associated with an increased risk of death. Despite the poor prognosis, there was significant improvement in overall survival in the most recent years in this sample, mainly due to advances in diagnosis and reconstruction techniques.

Evaluation of the prognostic impact of postoperative adjuvant radiotherapy on head and neck mucosal melanoma: a meta-analysis.

BackgroundHead and neck mucosal melanoma (HNMM) is a rare type of malignant tumor that frequently exhibits postoperative recurrence and distant metastasis. Many clinicians administer postoperative adjuvant radiotherapy to improve patient prognosis and enhance quality of life; however, the effects of this treatment remain controversial. Therefore, in this study, a meta-analysis was performed to evaluate the practical value of postoperative adjuvant radiotherapy for head and neck mucosal melanoma.MethodsArticles in the PubMed, MEDLINE, Cochrane Library, Web of Science and EMBASE databases were systematically retrieved. Analyses were conducted to compare the impact of treatments involving postoperative radiotherapy with treatments entailing surgery alone on patient overall survival time, local recurrence and distant metastasis. The hazard ratio (HR) was used to evaluate the time-to-event data employing RevMan version 5.2 and Stata/SE version 13.0 software according to the principles specified for systematic reviews of interventions in the Cochrane handbook.ResultsTwelve cohort studies involving 1593 patients satisfied the desired conditions. In comparing surgery alone with postoperative radiotherapy, there was no significant difference regarding a decrease in the death risk in HNMM patients (HR, 1.07; 95 % CI, 0.95–1.2; p = 0.903; low heterogeneity, I2 = 0); this was also the case for sinonasal melanoma after subgroup meta-analysis (HR, 1.04; 95 % CI, 0.8–1.36; p = 0.983; low heterogeneity, I2 = 0 %). A sensitivity analysis and subgroup meta-analysis showed that disease progression was the main source of the instability in the results. Surgery combined with postoperative radiotherapy reduced the risk of local recurrence (HR, 0.51; 95 % CI, 0.35–0.76; p = 0.155) but did not reduce the risk of distant metastasis (HR, 2.26; 95 % CI, 1.01–5.05; p = 0.006).ConclusionsThis study demonstrated that for HNMM patients surgery is recommended if indicated, and surgery combined with postoperative radiotherapy is also recommended for dramatically improved local control of the tumor bed. For patients not suitable for surgical treatment, radiotherapy is still advised. To control distant metastasis and finally lower the risk of death, immunological therapy is another potential option whose therapeutic effect needs to be proved with more data from clinical trials.

Postoperative adjuvant radiotherapy improves loco-regional recurrence of head and neck mucosal melanoma

Primary head and neck mucosal melanoma (HNMM) is a rare tumor with a poor prognosis. Controversy remains as to whether postoperative adjuvant radiotherapy (PORT) achieves a significant benefit in HNMM treatment. Because of the lack of available conclusive prospective data, we performed a systematic review and meta-analysis of all relevant available studies to clarify the benefits of PORT. A comprehensive literature search of PubMed and Google Scholar electronic databases was conducted to collect relevant studies until April 30, 2014. Studies published in the English language comparing surgery alone and surgery plus PORT for HNMM were included, with more than 15 study populations. All statistical analyses were performed using STATA version 12.0. A total of 423 patients were available from eight studies and the median sample size was 53 cases. The median follow-up time was 38.2 months (range 18.3–65.2 months). There was a positive association between PORT and loco-regional recurrence of HNMM (odds ratio [OR] = 0.36, 95% confidence interval [CI] = 0.22–0.60, P = 0.000). No associations were found between the PORT and 3-year and 5-year overall survival (OS) (OR = 1.41, 95% CI = 0.94–2.09, P = 0.093 and OR = 1.06, 95% CI = 0.70–1.61, P = 0.161, respectively). PORT had no impact on 3-year and 5-year OS (hazard ratio [HR] = 1.14, 95% CI = 0.80–1.61, P = 0.472 and HR = 1.34, 95% CI = 0.97–1.85, P = 0.227, respectively). PORT improved loco-regional recurrence of HNMM independent of OS.

Demographics and treatment trends in sinonasal mucosal melanoma

To evaluate the population characteristics of mucosal melanoma of the nasal cavity and paranasal sinuses and determine the impact of the new staging classification. Analysis of a national database. Patients were identified from the Surveillance, Epidemiology, and End Results tumor registry data with mucosal melanoma of the nasal cavity and paranasal sinuses between 2000 and 2007. Tumors were classified using the American Joint Committee on Cancer (AJCC) 6th edition site-specific staging as well as 7th edition staging for head and neck mucosal melanoma (HNMM). Incidence rates and descriptive statistics were calculated, and multivariate analysis was performed to examine the impact of demographic factors and staging on survival. A total of 304 patients were identified. The incidence rate was 0.05 per 100,000. Fifty-six percent were female, 92% were >50 years old, and more than 90% were Caucasian; 81.6% of patients were treated with surgery, and 38.5% of patients received postoperative radiation. Overall, the 5-year survival rate was 24.2%. Significant differences in survival were observed for surgery with radiation (P = .005) and surgery alone (P = .04) compared with radiation alone. TNM staging using the AJCC 6th and 7th edition classification schemes yielded similar survival curves. However, the new classification for HNMM allows for better delineation of stage IV disease, revealing slightly improved survival for stage IVA disease. HNMM is a rare disease with a poor prognosis. Surgery remains the treatment of choice, with some role for adjuvant therapy. The new staging classification for HNMM appears to more efficiently stage this disease. Demographics and therapeutic findings are discussed.

Postoperative Radiotherapy in Head and Neck Mucosal Melanoma

to report patterns of failure according to treatment modality, with an emphasis on the role of postoperative radiotherapy in patients with localized head and neck mucosal melanoma (HNMM) treated during a 28-year period in a multi-institutional setting. retrospective review. french medical institutions. a total of 160 patients with nonmetastatic HNMM treated from 1980 through 2008. treatment modality consisted of surgery alone (hereinafter, S group) (n = 82 patients) or with postoperative radiotherapy (hereinafter, SRT group) (n = 78). Patients and tumor characteristics were similar in the 2 groups. There was a nonsignificant trend (P = .11) for more locally advanced tumor stage (38.9%) in the SRT group compared with the S group (24.5%). patients in the S group had an increased probability of locoregional recurrence as a first event (55.6%) compared with those in the SRT group (29.9%; P < .01). After adjusting for tumor stage (T1/T2 vs T3/T4), the subdistribution hazard ratio of locoregional relapse was 0.31, (95% confidence interval [CI], 0.15-0.61; P < .01).The rate of distant metastasis as a first event was significantly higher in the SRT group (40.6%) compared with the S group (19.9%; P = .01). Regardless of their treatment, patients who had a locoregional relapse during follow-up had an increased risk of subsequent distant metastasis (hazard ratio, 3.07; 95% CI, 1.65-5.67) and death (hazard ratio, 3.01; 95% CI, 1.91-4.78). this large retrospective study suggests that postoperative radiotherapy improves the locoregional control of HNMM. The higher rate of distant metastasis was due to more advanced disease in the SRT group.

Postoperative radiotherapy for primary mucosal melanoma of the head and neck

Primary head and neck mucosal melanoma (HNMM) has a poor prognosis with a low local control rate and frequent distant metastases. The objective of the current study was to determine the impact of postoperative radiotherapy on local control and survival. One hundred forty-two patients with primary HNMM treated between 1979 and 1997 were reviewed. Of these, 69 patients with confirmed primary mucosal melanoma, absence of metastatic disease, and definitive management by surgery with or without postoperative radiotherapy and follow-up at the Institut Gustave-Roussy (Villejuif) were selected. The site of primary HNMM was sinonasal in 46 patients, oral in 19 patients, and pharyngolaryngeal in 4 patients. Twenty-two patients (32%) had a locally advanced tumor (T3-T4) and 17 patients had regional lymph node metastases after pathologic examination (pN > 0). Thirty patients underwent surgery alone and 39 received postoperative radiotherapy. Patients with locally advanced tumors had received postoperative radiotherapy more frequently than those with small tumors (P = 0.02). Thirty-seven patients (54%) experienced local disease recurrence and 47 patients (68%) developed distant metastasis. The overall survival rates were 47% at 2 years and 20% at 5 years. In the Cox multivariate analysis, patients with early T-classification tumors who received postoperative radiotherapy had a better local disease-free survival (P = 0.004 and P = 0.05, respectively) compared with patients with late T-classification tumors who did not receive postoperative radiotherapy. Patients with advanced T-classification and pN > 0 stage had a shorter distant metastasis disease-free survival compared with patients with early T-classification and pN < 0 stage. Patients with advanced T-classification tumors had a shorter overall survival compared with patients with early T-classification tumors (P = 0.003). The prognosis of patients with HNMM was poor. Patients had a high rate of distant metastasis and a low rate of local control. The current study suggested that postoperative radiotherapy increased local control even for patients with small tumors.