Stains
ABCC2


Topic Completed: 23 July 2019

Revised: 23 July 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: ABCC2[TI] pathology

Rola Saleeb, M.D., Ph.D.
Page views in 2019 to date: 199
Cite this page: Saleeb R. ABCC2. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsABCC2.html. Accessed September 20th, 2019.
Definition / general
  • Adenosine triphosphate (ATP) binding cassette subfamily C member 2 (ABCC2) belongs to the C subfamily of the ABC transmembrane protein transporters
  • ABCC transporters are involved in active drug transportation
  • Contributes to chemotherapy resistance in some tumors by what is thought to be drug efflux mechanisms
    • Also called multidrug resistant protein 2 (MRP2)
Essential features
  • Diagnostically, ABCC2 is to be used together with morphology to subtype papillary renal cell carcinomas according to the proposed biological classification
  • ABCC2 has prognostic significance in some tumors, particularly papillary renal cell carcinoma, as well as breast, colon, ovary and fallopian tube
  • Might have predictive significance as has been implicated in chemotherapy resistance
Terminology
  • Adenosine triphosphate (ATP) binding cassette subfamily C member 2 (ABCC2)
  • Multidrug resistance associated protein 2 (MRP2)
  • Canalicular multispecific organic anion transporter 1 (CMOAT1)
  • Canalicular multidrug resistance protein (cMRP)
  • ABC30
  • Dubin-Johnson syndrome (DJS)
Pathophysiology
Clinical features
  • Germline mutations in ABCC2 are associated with autosomal recessive Dubin-Johnson syndrome
    • It is characterized by impaired secretion of conjugated bilirubin by hepatocytes
    • Grossly, the liver is black in appearance
    • Microscopically, there is accumulation of dark, coarsely granular pigment in the centrilobular zone
    • Electron microscopy shows the pigment accumulating in lysosomes
    • These patients are usually asymptomatic, with incidental detection of hyperbilirubinemia (Talaga: Dubin Johnson Syndrome, 2019)
Interpretation
  • Cytoplasmic staining consistently observed in all reported tumors and normal tissue
  • Additional nuclear staining reported in breast, ovary and fallopian tube
Uses by pathologists
Prognostic factors
Microscopic (histologic) description
  • Papillary renal cell carcinoma subtypes (Am J Surg Pathol 2017;41:1618):
    • Type 1 shows complete absence of ABCC2 staining
    • Type 2 exhibits strong diffuse staining equal to or stronger than the background renal tubules
    • Type 3 shows patchy staining weaker than the normal renal tubules
    • Type 4 (oncocytic low grade type) has a distinct morphology with reverse polarity nuclear pattern and shows a strong diffuse ABCC2 staining pattern; however, unlike type 2, they harbor GATA3+ nuclear staining (Am J Surg Pathol 2019 May 22 [Epub ahead of print])
    • Type 3 can be difficult to distinguish from type 1 on morphology alone without ABCC2 immunohistochemistry ancillary testing
Microscopic (histologic) images

Contributed by Rola Saleeb, M.D., Ph.D.

Papillary renal cell carcinoma type 1

Papillary renal cell carcinoma type 2


Papillary renal cell carcinoma type 3

Papillary renal cell carcinoma type 4

Positive staining - normal
  • Renal tubules (cytoplasmic)
  • Liver bile canaliculi (bile canaliculi expression)
  • Cerebral cortex (cytoplasmic)
  • Squamous epithelium (cytoplasmic)
  • Pancreatic acini (cytoplasmic)
  • Normal fallopian tube epithelium (cytoplasmic)
Positive staining - disease
Molecular / cytogenetics description
Board review question #1
A 56 year old man has an incidentally discovered renal mass, 4 cm in size. He was treated with partial nephrectomy. Microscopic examination shows a papillary renal cell carcinoma. You run an immunopanel including ABCC2 stain. Which pattern of staining reflects indolent tumor behavior?

  1. Complete absence of ABCC2 staining in both the tumor and the surrounding kidney
  2. Complete absence of ABCC2 staining in the tumor with preserved staining in renal tubules
  3. Strong diffuse staining equal to or stronger than the surrounding renal tubules
  4. Weak patchy staining, slightly weaker than the surrounding renal tubules
Board review answer #1
B. Complete absence of ABCC2 staining in the tumor with preserved staining in renal tubules. Papillary renal cell carcinoma type 1 shows complete absence of ABCC2 staining, while type 3 shows patchy weak staining and type 2 shows strong diffuse staining. Type 1 tumors with low ABCC2 levels by both mRNA and immunohistochemistry analysis have been shown in multiple studies to have excellent outcomes.

Reference: ABCC2

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