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DOG1 expression is common in human tumors: A tissue microarray study on more than 15,000 tissue samples.

Kristina Jansen1, Nagina Farahi1, Franziska Büscheck1

  • 1Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Pathology, Research and Practice
|October 30, 2021
PubMed
Summary

Discovered on GIST1 (DOG1) is a channel highly expressed in GIST. This study found DOG1 in 67 tumor types, expanding its diagnostic relevance beyond GIST, especially in epithelioid neoplasms.

Keywords:
DOG1immunohistochemistrytissue micro array, human cancer

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Area of Science:

  • Oncology
  • Molecular Biology
  • Immunohistochemistry

Background:

  • Discovered on GIST1 (DOG1) is a calcium-activated chloride and bicarbonate channel.
  • DOG1 is highly expressed in interstitial cells of Cajal and gastrointestinal stromal tumors (GIST).
  • The expression patterns of DOG1 in various normal tissues and tumor types require systematic investigation.

Purpose of the Study:

  • To systematically determine the expression of DOG1 in a wide range of human tumor entities and normal tissue types.
  • To assess the diagnostic utility of DOG1 beyond GIST, particularly in epithelioid neoplasms.
  • To investigate the correlation between DOG1 expression and clinicopathological parameters, including tumor aggressiveness, prognosis, estrogen receptor status, and HPV infection.

Main Methods:

  • Immunohistochemistry was performed on a comprehensive tissue microarray (TMA) comprising 15,965 tumor samples (121 types) and 608 normal tissue samples (76 types).
  • Statistical analysis was used to correlate DOG1 expression with histopathological parameters and clinical factors in specific cancer types.

Main Results:

  • DOG1 immunostaining was detected in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), and others.
  • Low-level DOG1 expression was observed in an additional 17 tumor entities.
  • DOG1 expression was not related to tumor aggressiveness or prognosis in breast, bladder, ovarian, endometrial, stomach, and thyroid cancers. High DOG1 expression correlated with estrogen receptor positivity in breast cancer and absence of HPV in squamous cell carcinomas.

Conclusions:

  • DOG1 is expressed in numerous tumor types beyond GIST, suggesting a broader diagnostic application.
  • While DOG1 is a key marker for GIST in spindle cell tumors, its expression in epithelioid neoplasms indicates a wider differential diagnosis.
  • The study identifies several tumor entities with significant DOG1 expression, comparable to levels seen in GIST.