Stains
Topoisomerase II alpha (TOP2A)

Author: Semir Vranic, M.D. (see Authors page)

Revised: 4 December 2015, last major update June 2010

Copyright: (c) 2002-2015, PathologyOutlines.com, Inc.

General
  • Topoisomerases are enzymes that wind and unwind DNA to facilitate protein synthesis and DNA replication (Wikipedia)
  • Topoisomerase IIA cuts both strands of the DNA helix to unwind them (Wikipedia)
  • Expression is predictive of prognosis in various malignancies
  • Also called Topo II alpha (TOP2A)
  • Topo II labeling index: number of TOP2A positive staining nuclei divided by the total number of tumor cells counted multiplied by 100
Pathophysiology
Interpretation
  • The best tool and cutoff values for TOP2A assessment are unknown
  • The most commonly used method is TOP2A gene analysis by FISH (Pathol Res Pract 2010;206:156)
  • TOP2A protein expression by immunohistochemistry is also commonly used
Uses by Pathologists
Micro Images

Image hosted on Flickr
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Breast carcinoma, c/o Semir Vranic, M.D.


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Breast carcinomas

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Hodgkin lymphoma

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Lung cancer: small cell (+) versus adenocarcinoma (focal +)

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Meningiomas

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Pancreatic endocrine neoplasm

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Prostate, hormone insensitive

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Prostate, various

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Seminoma



Images hosted on Nature.com:

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Breast carcinoma

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Myeloma (fig A)

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Ovarian tumors

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Pituitary adenoma

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Pituitary carcinoma

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Rectal crypts in normal tissue

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Thyroid carcinoma

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Thyroid: anaplastic carcinoma

Positive Staining - Normal
  • Tissues with proliferating cells, especially spermatocytes, germinal centers and proliferative endometrium (Mod Pathol 1997;10:168)
Positive Staining - Not Malignant
Positive Staining - Malignant
Negative Staining
  • Terminally differentiated tissues (because TOP2A is not expressed in G0 phase): cerebral cortex, skeletal muscle and nerve
  • Rare positive cells in breast, salivary gland and kidney (Mod Pathol 1997;10:168)
Molecular / Cytogenetics Images

Image hosted on Flickr

TOP2A CEP17 FISH no gene amplification, c/o Semir Vranic, M.D.



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Breast carcinoma: FISH of HER2 and TOP2A