Background-Merkel cell carcinoma (MCC) is an aggressive skin cancer with a mortality of 33%. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. No systematic analysis has been published to define the clinical features that are characteristic of MCC.
Background The management of Merkel cell carcinoma (MCC) has been complicated by a lack of detailed prognostic data and by the presence of conflicting staging systems. Objective To determine the prognostic significance of tumor size, clinical vs pathologic nodal evaluation, and extent of disease at presentation and thereby derive the first consensus staging/prognostic system for MCC. Methods 5,823 prospectively enrolled MCC cases from the National Cancer Data Base (NCDB) had follow-up data (median 64 months) and were used for prognostic analyses. Results At 5 years, overall survival was 40% and relative survival (compared to age- and sex-matched population data) was 54%. Among all MCC cases, 66% presented with local, 27% with nodal and 7% with distant metastatic disease. For cases presenting with local disease only, smaller tumor size was associated with better survival (stage I: ≤2cm: 66% relative survival at five years; stage II: >2cm: 51%; p<0.0001). Patients with clinically local-only disease and pathologically proven negative nodes had better outcome (76% at five years) than those who only underwent clinical nodal evaluation (59%, p<0.0001). Limitations The NCDB does not capture disease-specific survival. Overall survival for MCC patients was therefore used to calculate relative survival based on matched population data. Conclusion Although the majority (68%) of MCC patients in this nationwide cohort did not undergo pathologic nodal evaluation, this procedure may be indicated in many cases as it improves prognostic accuracy and has important treatment implications for those found to have microscopic nodal involvement.
Purpose Merkel cell carcinoma (MCC) is a polyomavirus-associated skin cancer that is frequently lethal and lacks established prognostic biomarkers. This study sought to identify biomarkers that improve prognostic accuracy and provide insight into MCC biology. Patients and Methods Gene expression profiles of 35 MCC tumors were clustered based on prognosis. The cluster of genes overexpressed in good-prognosis tumors was tested for biologic process enrichment. Relevant mRNA expression differences were confirmed by quantitative polymerase chain reaction and immunohistochemistry. An independent set of 146 nonoverlapping MCC tumors (median follow-up, 25 months among 116 living patients) was employed for biomarker validation. Univariate and multivariate Cox regression analyses were performed. Results Immune response gene signatures were prominent in patients with good prognoses. In particular, genes associated with cytotoxic CD8+ lymphocytes were overexpressed in tumors from patients with favorable prognoses. In the independent validation set, cases with robust intratumoral CD8+ lymphocyte infiltration had improved outcomes (100% MCC-specific survival, n = 26) compared with instances characterized by sparse infiltration (60% survival, n = 120). Only stage and intratumoral CD8 infiltration (but not age, sex, or CD8+ lymphocytes localized to the tumor-stroma interface) were significant in both univariate and multivariate Cox regression analyses. Notably, traditional histologic identification of tumor-infiltrating lymphocytes was not a significant independent predictor of survival. Conclusion Intratumoral CD8+ lymphocyte infiltration can be readily assessed on paraffin-embedded tissue, is independently associated with improved MCC-specific survival, and therefore, may provide prognostic information that enhances established MCC staging protocols.
BackgroundMerkel cell polyomavirus (MCPyV) has been detected in approximately 75% of patients with the rare skin cancer Merkel cell carcinoma. We investigated the prevalence of antibodies against MCPyV in the general population and the association between these antibodies and Merkel cell carcinoma.MethodsMultiplex antibody-binding assays were used to assess levels of antibodies against polyomaviruses in plasma. MCPyV VP1 antibody levels were determined in plasma from 41 patients with Merkel cell carcinoma and 76 matched control subjects. MCPyV DNA was detected in tumor tissue specimens by quantitative polymerase chain reaction. Seroprevalence of polyomavirus-specific antibodies was determined in 451 control subjects. MCPyV strain–specific antibody recognition was investigated by replacing coding sequences from MCPyV strain 350 with those from MCPyV strain w162.ResultsWe found that 36 (88%) of 41 patients with Merkel cell carcinoma carried antibodies against VP1 from MCPyV w162 compared with 40 (53%) of the 76 control subjects (odds ratio adjusted for age and sex = 6.6, 95% confidence interval [CI] = 2.3 to 18.8). MCPyV DNA was detectable in 24 (77%) of the 31 Merkel cell carcinoma tumors available, with 22 (92%) of these 24 patients also carrying antibodies against MCPyV. Among 451 control subjects from the general population, prevalence of antibodies against human polyomaviruses was 92% (95% CI = 89% to 94%) for BK virus, 45% (95% CI = 40% to 50%) for JC virus, 98% (95% CI = 96% to 99%) for WU polyomavirus, 90% (95% CI = 87% to 93%) for KI polyomavirus, and 59% (95% CI = 55% to 64%) for MCPyV. Few case patients had reactivity against MCPyV strain 350; however, indistinguishable reactivities were found with VP1 from strain 350 carrying a double mutation (residues 288 and 316) and VP1 from strain w162.ConclusionInfection with MCPyV is common in the general population. MCPyV, but not other human polyomaviruses, appears to be associated with Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a rising incidence (1500 U.S. cases per year) that now exceeds that of cutaneous T-cell lymphoma and a mortality (33%) exceeding that of melanoma. Despite this impact, little is known about its biology. Recent studies have shown that Ras/MAP kinase activity is absent and possibly detrimental to this cancer. This makes MCC distinct from other UV--induced skin cancers and highlights the question of what drives this malignancy.
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high-resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10 and 13. MCC tumors with less genomic aberration were associated with improved survival (p=0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26% of tumors, a deletion of 13q14-21 was recurrent in 26% of tumors and contains the well-characterized tumor suppressor RB1, and a novel focal amplification at 1p34 was present in 39% of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, while 4/4 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.
BACKGROUND:Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high risk of lymph node involvement. To the authors' knowledge, few data have been published to date regarding the optimal regional therapy for lymph node‐positive patients. This cohort study was performed to analyze the outcomes of patients with lymph node‐positive MCC treated with lymph node irradiation as definitive therapy compared with completion lymphadenectomy (CLND).METHODS:Fifty patients with lymph node involvement of MCC at presentation and adequate follow‐up data were included in this analysis. Forty‐three of these patients were enrolled and followed prospectively. Twenty‐six patients presented with microscopic lymph node disease, and 24 patients presented with palpable lymph node involvement.RESULTS:Regional control for patients with microscopically involved lymph nodes was 100% regardless of treatment modality—definitive lymph node irradiation (n = 19) or CLND ± radiotherapy (n = 7) with median follow‐up of 18 months. Patients with clinically positive lymph nodes had 2‐year regional recurrence‐free survival rate of 78% and 73% in the definitive lymph node irradiation (n = 9) and CLND ± radiotherapy (n = 15) groups, respectively (P = .8) with a median follow‐up of 16 months.CONCLUSIONS:To the best of the authors' knowledge, the current study is the largest series published to date of radiation monotherapy as regional treatment for lymph node‐positive MCC. Lymph node irradiation alone to positive regional lymph nodes was found to confer an excellent regional control rate that was comparable to CLND for both microscopic and palpable lymph node disease. There was no difference noted with regard to overall survival. Given their similar efficacy, the choice between these lymph node therapies may be based on the clinical scenario and anticipated side effect profiles. Cancer 2010. © 2010 American Cancer Society.
BACKGROUND The effects of primary tumor size on nodal involvement and of number of involved nodes on survival have not been examined in a national database of Merkel cell carcinoma. OBJECTIVE Analyze a retrospective cohort of MCC patients from the largest US national database to assess the relationships between these clinical parameters and survival. METHODS 8,044 MCC cases in the National Cancer Data Base (NCDB) were analyzed. RESULTS There was a 14% risk of regional nodal involvement for 0.5 cm tumors which increased to 25% for 1.7cm (median sized) tumors and to >36% for ≥6 cm tumors. The number of involved nodes was strongly predictive of survival (0 nodes, 76% five-year relative survival; 1 node, 50%; 2 nodes, 47%; 3–5 nodes, 42%; and ≥ 6 nodes, 24%; p<0.0001 for trend). Younger and or male patients were more likely to undergo pathological nodal evaluation. LIMITATIONS NCDB does not capture disease-specific survival. Hence, relative survival was calculated by comparing overall survival to age- and sex-matched US population data. CONCLUSION Pathologic nodal evaluation should be considered even for patients with small primary MCC tumors. The number of involved nodes is strongly predictive of survival and may help improve prognostic accuracy and management.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.