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• Loss of beta catenin membrane expression with overexpression in the cytoplasm and nucleus is associated with various carcinomas, including breast, colon and pancreas
  • Breast
    • Nuclear and cytoplasmic accumulation in basal-like breast cancers
    • Reduced membrane expression observed with tumor progression (Am J Pathol 2010;176:2911)
  • Colon
    • Beta catenin plays a critical role in tumorigenesis (activating Wnt signaling mutations present in 90% of colon cancers) (Sci Rep 2020;10:2957)
    • Membrane expression in normal colorectal epithelium
    • Staining pattern shifts to cytoplasmic / nuclear in tumor tissue (World J Gastroenterol 2008;14:3866)
  • Thyroid
    • Wnt pathway important for anaplastic and possibly papillary thyroid carcinomas
    • Shifts from membrane location to cytoplasmic in malignant tumors (Front Endocrinol (Lausanne) 2012;3:31)
  • Uterus
    • Endometrial carcinoma is associated with beta catenin mutations (exon 3 in CTNNB1) (Front Oncol 2022;12:1009345)
  • Liver
    • Beta catenin expression is membranous for normal hepatocytes
    • Mutations in CTNNB1 occur in about a third of human hepatocellular carcinomas (HCC) (J Clin Invest 2022;132:e154515)
  • Pancreas
    • Strong membrane staining in primary tumors of pancreatic neuroendocrine tumors (PanNETs); nuclear staining present in advanced stages including metastasis (World J Gastrointest Oncol 2016;8:615)
  • Low grade sinonasal adenocarcinoma (nuclear localization) (Case Rep Pathol 2018;2018:8741017)
  • Lung
    • Reduced membrane expression of beta catenin with increased expression in cytoplasm and nucleus for non-small cell lung cancer (NSCLC) (Transl Lung Cancer Res 2017;6:97)
  • Skin (melanoma)
    • Loss of membrane expression as melanoma progresses from primary to metastatic
    • Low frequency of CTNNB1 genetic mutations in melanomas, which does not correlate with nuclear expression (Mod Pathol 2002;15:454)

Contributed by Pamela Wirth, Ph.D. (source: University of Toronto and Human Protein Atlas),
Farres Obeidin, M.D., Christian M. Schürch, M.D., Ph.D. and Hyunkyu Shin, M.D.

Which exon mutation in beta catenin is most commonly detected in endometrial carcinomas, resulting in increased nuclear expression?

1. Exon 3
2. Exon 7
3. Exon 8
4. Exon 13

A. Exon 3. Studies have demonstrated that 30 - 60% of endometrial carcinoma cases exhibit nuclear accumulation of beta catenin in tumor cells because of mutations in exon 3 of CTNNB1. Answers B and C and are incorrect because these mutations are not commonly found in endometrial carcinoma and only weakly activate beta catenin in some other cancers like hepatocellular carcinomas. Answer D is incorrect because mutations in exon 13 are not associated with endometrial carcinomas but are more consistent with CTNNB1 syndrome with symptoms of cognitive and motor impairment.

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Reference: Beta catenin

Which of the following staining patterns for beta catenin would be most common in pancreatic tissue?

1. Increased membranous expression of beta catenin in stages III - IV of pancreatic tumors
2. Loss of membrane expression in ductal cells of normal pancreatic tissue
3. Increased nuclear expression of beta catenin in solid pseudopapillary neoplasm
4. Normal pancreatic tissue with increased nuclear beta catenin expression

C. Increased nuclear expression of beta catenin in solid pseudopapillary neoplasm. Solid pseudopapillary neoplasms of the pancreas frequently harbor genetic mutations within the beta catenin gene, resulting in aberrant nuclear expression of the protein by IHC. Answer B is incorrect because beta catenin is predominantly located and positively expressed on the membrane of ductal cells in normal pancreatic tissue. Answer A is incorrect because beta catenin expression on the membrane is lost in later stages of pancreatic tumors. Answer D is incorrect because nuclear expression of beta catenin is associated with more advanced stages of pancreatic tumors.

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Reference: Beta catenin