Stains & CD markers
YAP1

Editorial Board Member: Borislav A. Alexiev, M.D.
Y. Albert Yeh, M.D., Ph.D.

Topic Completed: 3 May 2021

Minor changes: 12 August 2021

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PubMed Search: YAP1[TI] stains

Y. Albert Yeh, M.D., Ph.D.
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Cite this page: Yeh YA. YAP1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsyap1.html. Accessed October 28th, 2021.
Definition / general
  • YAP1 (yes associated protein 1) is a transcriptional regulator that activates gene transcription involved in cellular survival and proliferation and suppresses apoptotic genes
Essential features
Terminology
  • YAP
  • YAP2
  • YAP65
  • YKI
  • Protein yorkie homolog
  • COB1
Pathophysiology
  • When Hippo signaling pathway is on, mammalian STE20-like protein kinase 1 / 2 (MST1 / 2) and salvador family WW domain containing protein 1 (SAV1) are activated
  • LATS1 / 2 kinases phosphorylate YAP or transcriptional coactivator with PDZ binding motif (TAZ) through the interaction with MOB kinase activator 1A / 1B (MOB1A / 1B)
  • As a result, the active phosphorylated YAP / TAZ binds to 14-3-3, leading to cytoplasmic retention and ubiquitin mediated proteasomal degradation
  • Neurofibromin 2 (NF2) can activate LATS1 / 2 through a nonkinase reaction
  • Unknown kinase(s) may phosphorylate LATS1 / 2 in an MST1 / 2 independent fashion
  • When the Hippo signaling pathway is off, YAP / TAZ are not phosphorylated by LATS1 / 2
  • YAP and TAZ translocate to the nucleus and bind to transcription factor TEAD, leading to transcription activation of target genes, including AMOTL2, AREG, BIRC5, CTGF and CYR61, and promoting cell survival and proliferation (Nat Rev Cancer 2015;15:73)
Diagrams / tables

Images hosted on other servers:
Hippo / YAP signaling pathway

Hippo / YAP signaling pathway

Clinical features
Interpretation
  • Cytoplasmic and predominantly nuclear staining
Uses by pathologists
Prognostic factors
Microscopic (histologic) description
  • Small cell neuroendocrine carcinoma of the prostate is negative for YAP1 (see Microscopic images 1, 2, 3)
  • Low risk prostatic adenocarcinoma cells (Gleason score 3+3=6, grade group 1) show focally positive nuclear staining for YAP1 (see Microscopic image 4)
  • In prostatic adenocarcinoma, Gleason score 3+4=7 (grade group 2), many carcinoma cells show positive nuclear staining for YAP1 in the glomeruloid structure (Gleason pattern 4) (see Microscopic image 5)
  • In high risk prostatic adenocarcinoma (Gleason 4+4=8, 4+4=9, 5+5=10), tumor cells are diffusely stained positive for YAP1 (see Microscopic images 6, 7, 8)
  • In benign prostatic tissue, basal cells, fibromuscular stroma and smooth muscles are stained positive for YAP1; benign prostatic luminal cells show negative staining for YAP1 (see Microscopic images 9, 10)
Microscopic (histologic) images

Contributed by Y. Albert Yeh, M.D., Ph.D.
YAP1 in neuroendocrine carcinoma YAP1 in neuroendocrine carcinoma YAP1 in neuroendocrine carcinoma

YAP1 in neuroendocrine carcinoma

YAP1 in prostatic adenocarcinoma YAP1 in prostatic adenocarcinoma

YAP1 in prostatic adenocarcinoma


YAP1 in prostatic adenocarcinoma YAP1 in prostatic adenocarcinoma YAP1 in prostatic adenocarcinoma

YAP1 in prostatic adenocarcinoma

YAP1 in benign prostate

YAP1 in benign prostate

YAP1 in skeletal muscle

YAP1 in skeletal muscle



Contributed by Meenakshi Vij Gupta, M.D.
Missing Image

Prostate

Small intestine

Colon: adenocarcinoma

Positive staining - normal
Positive staining - disease
Negative staining
Molecular / cytogenetics description

YAP1 gene fusion Tumor type Reference
YAP1-MAMLD1 Supratentorial ependymoma Cancer Cell 2015;27:728
YAP1-FAM118B Supratentorial ependymoma Cancer Cell 2015;27:728
Meningioma Am J Surg Pathol 2021;45:329
YAP1-MAML2 Pediatric meningioma Acta Neuropathol 2020;139:215
Poroma and porocarcinoma J Clin Invest 2019;129:3827
Retiform and composite hemangioendothelioma Am J Surg Pathol 2020;44:1677
Metaplastic thymoma Mod Pathol 2020;33:560
YAP1-PYGO1 Pediatric meningioma Acta Neuropathol 2020;139:215
YAP1-LMO1 Pediatric meningioma Acta Neuropathol 2020;139:215
YAP1-NUTM1 Porocarcinoma J Clin Invest 2019;129:3827
YAP1-TFE3 Epithelioid hemangioendothelioma Case Rep Gastrointest Med 2019;2019:7530845
YAP1-KMT2A Sclerosing epithelioid fibrosarcoma Am J Surg Pathol 2020;44:368
HMGA2-YAP1 Aggressive angiomyxoma BMJ Case Rep 2019;12:e227475
Molecular / cytogenetics images

Images hosted on other servers:

YAP1-TFE3 in
epithelioid
hemangioendothelioma

Sample pathology report
  • Skin, right lower leg, excision:
    • Malignant cutaneous basaloid tumor with YAP1-NUTM1 fusion (see comment)
    • Comment: The skin shows an infiltrating tumor composed of small basaloid cells arranged in anastomosing cords and nests with cystic formation. Tumor cells invade adipose tissue beneath the dermis. Focal tumor necrosis is present. Immunohistochemical stain shows positive nuclear staining of the N terminus of YAP1 but loss of staining of the C terminus. Fluorescence in situ hybridization using YAP1 break apart probe confirms rearrangement of YAP1 gene. RT-PCR testing reveals YAP1-NUTM1 translocation.
Board review style question #1

Which of the following biomarker expressions shown in the photomicrograph is lost in neuroendocrine carcinoma?

  1. CD56
  2. Chromogranin
  3. INSM1
  4. YAP1
Board review style answer #1
D. YAP1

Comment Here

Reference: YAP1
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