The implications of TrkA and MET aberrations in de novo salivary duct carcinoma

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Cannulation of the Mouse Submandibular Salivary Gland via the Wharton's Duct
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Cannulation of the Mouse Submandibular Salivary Gland via the Wharton's Duct

Published on: May 14, 2011

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Hyang Joo Ryu1, Yoon Woo Koh2, Sun Och Yoon1

  • 1Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea.

Human Pathology
|May 13, 2018
PubMed

Insights

Salivary duct carcinoma (SDC) is aggressive. MET and tropomyosin-receptor kinase (Trk) show potential as therapeutic targets, especially TrkA in HER2-negative SDC, which is linked to poor prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Salivary duct carcinoma (SDC) is an aggressive cancer with limited treatment options.
  • While HER2-positive SDC can be treated with anti-HER2 therapy, targets for HER2-negative SDC remain largely unknown.
  • Receptor tyrosine kinases MET and tropomyosin-receptor kinase (Trk) are emerging as potential therapeutic targets in various cancers.

Purpose of the Study:

  • To investigate MET and Trk family members (TrkA, TrkB, TrkC) as potential therapeutic targets in de novo salivary duct carcinoma.
  • To evaluate the expression and genetic status of MET and HER2 in SDC.
  • To determine the prognostic significance of TrkA expression, particularly in HER2-negative SDC.

Main Methods:

  • Analysis of 28 surgically resected SDC cases using immunohistochemistry for c-erb2, TrkA, TrkB, TrkC, and c-MET.
  • Assessment of HER2 and MET gene status via dual-color silver in situ hybridization.
  • Correlation of receptor expression and gene status with clinical outcomes, including overall survival.

Main Results:

  • 64.3% of SDC cases were HER2-positive.
  • MET expression and copy number gain/amplification were frequent (57.1% and 10.7%, respectively).
  • High TrkA expression was observed in a subset of cases and was significantly associated with inferior overall survival in HER2-negative SDC.

Conclusions:

  • MET and TrkA are frequently altered and expressed in SDC.
  • High TrkA expression is a potential indicator of poor prognosis in HER2-negative SDC.
  • TrkA and MET represent promising therapeutic targets for SDC, particularly for HER2-negative subtypes.
Keywords:
BiomarkerMETPrognosisSalivary duct carcinomaTrk

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