Evidence map›Paper›PMID 26022453›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2015

Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma.

Melissa P Pulitzer, A Rose Brannon, Michael F Berger, Peter Louis, Sasinya N Scott, Achim A Jungbluth, Daniel G Coit, Isaac Brownell, Klaus J Busam

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.Journal of the National Comprehensive Cancer Network : JNCCN · 2018
    Guideline
  2. Review
  3. Diagnostic Utility and Clinicopathologic Associations of Histone H3 Lysine 27 Trimethylation (H3K27me3) Immunohistochemistry for Merkel Cell Carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. RB1-deficient squamous cell carcinoma: the proposed source of combined Merkel cell carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Morphologic and immunophenotypical features distinguishing Merkel cell polyomavirus-positive and negative Merkel cell carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019
    Article
  17. Review
  18. Article
  19. Article
  20. Update on Merkel Cell Carcinoma.Head and neck pathology · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Melissa P PulitzerDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
A Rose BrannonDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Michael F BergerDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Peter LouisDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Sasinya N ScottDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Achim A JungbluthDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Daniel G CoitDepartment of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Isaac BrownellDermatology Branch, National Cancer Institute, National Institute of Health, Washington, DC, USA.
Klaus J BusamDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Memorial Sloan Kettering Cancer Center · USNational Cancer Institute · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Molecular pathogenesis of Merkel cell carcinomaZIABC011394 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BROWNELL, ISAAC · 2011 to 2021
$6.8M
Translational Research in Oncology Training ProgramT32CA160001 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SAWYERS, CHARLES L. · 2011 to 2020
$2.0M
NCI NIH HHS P30 CA008748NCI NIH HHS P30CA008748NCI NIH HHS T32 CA160001
6 · The paper itself

Abstract

Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven 'pure' Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52-89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.

Indexed as

Biomarkers, TumorImmunohistochemistryAgedAged, 80 and overCarcinoma, Merkel CellCarcinoma, Squamous CellDNA Mutational AnalysisFemaleGenotypeHigh-Throughput Nucleotide SequencingHumansKeratin-20MaleMiddle AgedMutationNeoplasms, Complex and MixedBiomarkers, TumorKeratin-20KRT20 protein, humanNeurofilament ProteinsRetinoblastoma ProteinTP53 protein, humanTP63 protein, humanTranscription FactorsTumor Suppressor Protein p53Tumor Suppressor Proteins

Identifiers

PMID26022453
PMCPMC4920599
OpenAlexW1909163072

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.