Merkel cell carcinoma

Andea, Aleodor A.; Coit, Daniel G.; Amin, Bijal; Busam, Klaus J.

doi:10.1002/cncr.23874

Cited by 194 publications

(48 citation statements)

References 34 publications

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“…Prognosis in MCC is historically directed by the American Joint Committee on Cancer staging system, but this remains controversial because conclusive evidence that stage is the most rigorous surrogate of outcome for all patients is lacking (4, 6, 7, 25, 26). Additional biologically meaningful biomarkers predictive of clinical outcome in MCC have thus been investigated, but with similarly controversial and inconsistent conclusions (25, 27, 28).…”

Section: Discussionmentioning

confidence: 99%

“…Additional biologically meaningful biomarkers predictive of clinical outcome in MCC have thus been investigated, but with similarly controversial and inconsistent conclusions (25, 27, 28). More recent efforts have implicated the tumor-associated immune cell infiltrate as a potentially robust indicator of clinical behavior in MCC (4, 26). …”

Section: Discussionmentioning

confidence: 99%

“…However, the significance of individual prognostic indicators, including clinical (sex, age, anatomic site of disease; refs. 3, 4, 7) and histopathologic features [tumor depth, tumor size, proliferative rate, perineural invasion (PNI), and lymphovascular invasion (LVI)] remain controversial (3, 4, 7, 10, 11). While most studies confirm that prognosis of MCC largely follows stage (in particular stages III and IV), TNM staging appears insufficient to predict outcome of MCC among patients presenting with stage I or II disease (7).…”

Section: Introductionmentioning

confidence: 99%

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Density, Distribution, and Composition of Immune Infiltrates Correlate with Survival in Merkel Cell Carcinoma

Feldmeyer

Hudgens

Ray-Lyons

et al. 2016

Clinical Cancer Research

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Purpose Merkel cell carcinoma (MCC) is an aggressive cancer with frequent metastasis and death with few effective therapies. Because programmed death ligand-1 (PD-L1) is frequently expressed in MCC, immune checkpoint blockade has been leveraged as treatment for metastatic disease. There is therefore a critical need to understand the relationships between MCPyV status, immune profiles, and patient outcomes. Experimental Design IHC for CD3, CD8, PD-1, PD-L1, and MCPyV T-antigen (to determine MCPyV status) was performed on 62 primary MCCs with annotated clinical outcomes. Automated image analysis quantified immune cell density (positive cells/mm2) at discrete geographic locations (tumor periphery, center, and hotspot). T-cell receptor sequencing (TCRseq) was performed in a subset of MCCs. Results No histopathologic variable associated with overall survival (OS) or disease-specific survival (DSS), whereas higher CD3+ (P = 0.004) and CD8+ (P = 0.037) T-cell density at the tumor periphery associated with improved OS. Higher CD8+ T-cell density at the tumor periphery associated with improved DSS (P = 0.049). Stratifying MCCs according to MCPyV status, higher CD3+ (P = 0.026) and CD8+ (P = 0.015) T-cell density at the tumor periphery associated with improved OS for MCPyV+ but not MCPyV− MCC. TCRseq revealed clonal overlap among MCPyV+ samples, suggesting an antigen-specific response against a unifying antigen. Conclusions These findings establish the tumor-associated immune infiltrate at the tumor periphery as a robust prognostic indicator in MCC and provide a mechanistic rationale to further examine whether the immune infiltrate at the tumor periphery is relevant as a biomarker for response in ongoing and future checkpoint inhibitor trials in MCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Density, Distribution, and Composition of Immune Infiltrates Correlate with Survival in Merkel Cell Carcinoma

Feldmeyer

Hudgens

Ray-Lyons

et al. 2016

Clinical Cancer Research

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“…11 An additional population-based cohort study from Finland using a different approach further supports an independent prognostic role for IT-CD8+ as well as CD3+ lymphocytes in MCC. 12 Classic H&E evaluation of tumor-infiltrating lymphocytes (TILs) has previously shown univariate but not independent significance 11,13 ; these studies are limited by technical difficulties in differentiating small, round, blue tumor cells from small, round, blue lymphocytes, particularly in the tumor field. We therefore suggest that immunohistochemical evaluation of cytotoxic intratumoral T-cell infiltration is a more sensitive means to assess the antitumor response.…”

Section: Discussionmentioning

confidence: 99%

CD8+ Lymphocyte Intratumoral Infiltration as a Stage-Independent Predictor of Merkel Cell Carcinoma Survival

Paulson

Iyer

Simonson

et al. 2014

American Journal of Clinical Pathology

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Objectives Intratumoral CD8+ lymphocytes (IT-CD8s) have shown promise as a prognostic indicator for Merkel cell carcinoma (MCC). We tested whether IT-CD8s predict survival among a population-based MCC cohort. Methods One hundred thirty-seven MCC cases that had not previously been analyzed for IT-CD8s were studied. Results Three-year MCC-specific survival rates were 56%, 72%, and 100% for patients with absent (n = 46), low (n = 85), and moderate or strong (n = 6) IT-CD8s, respectively. Increased IT-CD8s were associated with improved MCC-specific survival in a multivariate competing risk-regression analysis including stage, age, and sex (hazards ratio [HR] = 0.5; 95% confidence interval [CI] = 0.3-0.9). Although a similar trend was observed for overall survival, statistical significance was not reached (HR = 0.8; 95% CI = 0.6-1.0), likely because of the high rate of non-MCC deaths among older patients. Conclusions This study of prospectively captured MCC cases supports the concept that cellular immunity is important in MCC outcome and that CD8+ lymphocyte infiltration adds prognostic information to conventional staging.

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“…The size of the primary tumor below 2.0 cm is associated with better prognosis, unfortunately, because of the very rapid proliferation of tumor cells, and diagnostic difficulties delaying diagnosis, in most cases, patients are diagnosed with MCC at the stage when the primary lesion exceeds 2.0 cm [19]. The classification of TMN American Joint Committee on Cancer (AJCC) proposed a clinical staging of MCC (0 to IV) [20].…”

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confidence: 99%