Uroplakin II

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Stains & CD markers
Uroplakin II

Authors: Harsh Batra, M.B.B.S., D.C.P., D.N.B., Anil Parwani, M.D., Ph.D., M.B.A.

Editorial Board Member: Brandon Umphress, M.D.

Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.

Last author update: 22 September 2022

Last staff update: 5 September 2023

Copyright: 2022-2024, PathologyOutlines.com, Inc.

PubMed Search: Uroplakin II

Table of Contents

Cite this page: Batra H, Parwani A. Uroplakin II. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsuroplakinII.html. Accessed December 27th, 2024.

Definition / general

Uroplakin II, a 15kDa protein that is part of the uroplakin family (UP1a, UP1b, UPII and UPIII), which forms the urothelial plaque covering the apical surface of the urothelium

Essential features

Uroplakins are terminal differentiation products that are exclusively expressed in urothelial cells (Kidney Int 2009;75:1153)
15 kDa transmembrane protein involved in terminal differentiation of urothelium
Exists as a heterodimer along with UP1a (Kidney Int 2009;75:1153)
UPII IHC has significantly higher sensitivity (57% versus 50%) than UPIII and the same specificity (~99%) for urothelial carcinomas (Histopathology 2014;65:132)
Helpful in pinpointing the origin where secondary involvement by prostate adenocarcinoma or metastatic carcinoma may be positive for GATA3

Terminology

UPII, UPK2, UROII

Clinical features

Highly specific and moderately sensitive for urothelial carcinomas
Helpful in pinpointing the primary origin as urothelium in cases where GATA3 is inconclusive

Interpretation

Moderate to strong, predominantly membranous and cytoplasmic staining reaction in virtually all umbrella cells in the urethra (Appl Immunohistochem Mol Morphol 2022;30:326)
At least weak to moderate cytoplasmic and membranous staining reaction of the majority of intermediate urothelial cells (Hum Pathol 2007;38:1703)
Diffuse membranous staining in urothelial carcinoma cells (Appl Immunohistochem Mol Morphol 2022;30:326)

Uses by pathologists

Highly specific and moderately sensitive for urothelial carcinomas
Helpful in ascertaining the primary origin as urothelium, especially in cases where GATA3 is inconclusive
Currently recommended by ISUP as a second line additional marker to confirm urothelial primary (Am J Surg Pathol 2014;38:e20)

Prognostic factors

Loss of UPII seen more frequently in higher grade lesions (Arch Pathol Lab Med 2014;138:943)

Microscopic (histologic) images

Contributed by Charles C. Guo, M.D., Varsha Nair, M.D., Prih Rohra, M.D., Priya Rao, M.D. and Bogdan A. Czerniak, M.D., Ph.D.

Bladder, invasive urothelial carcinoma

Bladder, papillary urothelial carcinoma

Positive staining - normal

Apical expression in normal bladder epithelium (umbrella cells)
Intermediate cells in normal bladder epithelium

Positive staining - disease

Urothelial carcinoma
Ovarian Brenner tumor (Am J Surg Pathol 2003;27:1434)
Pleomorphic invasive lobular carcinoma (single study) (Dis Markers 2016;2016:2940496)
Apocrine metaplasia of breast (single study) (Dis Markers 2016;2016:2940496)
Apocrine carcinoma of breast (single study) (Dis Markers 2016;2016:2940496)
Adenocarcinoma of the colon (< 5% of cases) (Anticancer Res 2018;38:4759)
Squamous cell carcinoma of the lung (< 5% of cases) (Anticancer Res 2018;38:4759)
Endometrioid carcinoma of the uterine corpus (< 5% of cases) (Anticancer Res 2018;38:4759)
Classical hepatocellular carcinoma of the liver (10%) (seen only in intracytoplasmic hyaline bodies) (Anticancer Res 2018;38:4759)

Negative staining

Prostatic carcinoma (Anticancer Res 2018;38:4759)
Squamous cell carcinoma of bladder (Hum Pathol 2013;44:164)
Renal cell carcinoma (Histopathology 2014;65:132)
Classic invasive lobular carcinoma (Dis Markers 2016;2016:2940496)

Molecular / cytogenetics description

UPII mRNA expression in tissue and peripheral blood is associated with lymph node metastasis (J Pathol 2003;199:41)

Sample pathology report

Lymph node, pelvic node dissection:
- Metastatic urothelial carcinoma (see comment)
- Comment: Histologic sections show a lymph node with deposits of tumor cells in diffuse sheets and few with a trabecular pattern. The cells are round to polygonal, demonstrating moderate pleomorphism, inconspicuous nucleoli and high N:C ratios. Immunohistochemistry is positive for CK20, p63, GATA3, S100, uroplakin III and uroplakin II and negative for PSA, PSAP, NKX3.1 and prostein, suggesting a urothelial origin. Please correlate clinicoradiologically. Follow up is advised.

Board review style question #1

Uroplakin II forms a heterodimer with which other uroplakin?

UPIa
UPIb
UPIII
UPV

Board review style answer #1

A. UPIa

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Board review style question #2

Uroplakin II is expressed normally in which of the following?

Apical region (umbrella cells) of urothelium
Muscularis propria of bladder
Normal breast tissue
Prostate

Board review style answer #2

A. Apical region (umbrella cells) of urothelium

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Board review style question #3

Uroplakin II is highly specific for which of the following?

Infiltrating ductal carcinoma, NOS, breast
Lung adenocarcinoma
Prostate carcinoma
Urothelial carcinoma

Board review style answer #3

D. Urothelial carcinoma

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Board review style question #4

Which of the following is true regarding uroplakin II, as compared to uroplakin III?

Equally sensitive IHC marker for urothelial carcinoma
Less sensitive IHC marker for urothelial carcinoma
Less specific IHC marker for urothelial carcinoma
More sensitive IHC marker for urothelial carcinoma

Board review style answer #4

D. More sensitive IHC marker for urothelial carcinoma

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