DOG1 expression in neuroendocrine neoplasms: Potential applications and diagnostic pitfalls

Area of Science:

• Oncology
• Pathology
• Molecular Diagnostics

Background:

• Neuroendocrine neoplasms (NENs) are rare, heterogeneous tumors often presenting as metastatic or of unknown primary origin.
• Current immunohistochemical markers like Synaptophysin and Chromogranin-A confirm neuroendocrine differentiation, while others (TTF1, CDX2) suggest primary sites, but no marker distinguishes digestive tract origins.
• DOG1, typically used for gastrointestinal stromal tumors (GIST), is also found in other neoplasms.

Purpose of the Study:

• To evaluate the frequency, intensity, and pattern of DOG1 expression in a large cohort of neuroendocrine neoplasms (NENs) across different anatomical sites and tumor grades.
• To determine if DOG1 can serve as a marker for identifying the primary site of NENs, particularly in cases of unknown primary origin.
• To assess DOG1's utility in the differential diagnosis between NENs and epithelioid GIST.

Main Methods:

• Performed DOG1 immunostaining on a large cohort of neuroendocrine tumors and neuroendocrine carcinomas.
• Analyzed the frequency, intensity, and pattern of DOG1 expression in relation to anatomical site and tumor grade.
• Statistically evaluated the association between DOG1 expression and specific tumor characteristics.

Main Results:

• DOG1 expression was detected in a significant percentage of neuroendocrine neoplasms.
• A statistically significant association was found between DOG1 expression and neuroendocrine tumors originating from the gastrointestinal tract.
• DOG1 expression patterns varied across different anatomical sites and tumor grades.

Conclusions:

• DOG1 shows potential as a valuable marker for identifying the primary site of neuroendocrine neoplasms, especially in metastatic cases of unknown origin.
• The findings support the inclusion of DOG1 in marker panels for diagnosing NENs of unknown primary.
• Careful evaluation of DOG1 expression is recommended for gastrointestinal neoplasms, aiding in the differential diagnosis between NENs and epithelioid GIST.