Related Experiment Video
Updated: Jul 1, 2026
Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas
Published on: February 28, 2019
TRK-A, HER-2/neu, and KIT Expression/Activation Profiles in Salivary Gland Carcinoma
Tiziana Negri1, Elena Tamborini, Gian Paolo Dagrada
1Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract:
Salivary duct carcinomas (SDCs) and adenoid cystic carcinomas (ACCs) are the most aggressive and the most frequent carcinomas of the salivary glands, respectively. Little is known about them in terms of molecular/biochemical characterization and conventional treatments are ineffective. On cryopreserved material, we analyzed the expression/activation status of TRK-A, HER-2/neu, and KIT receptors by means of immunoprecipitation and Western blot analysis experiments, and the presence of their cognate ligands by means of Western blot analysis and/or reverse transcription-polymerase chain reaction in 9 SDCs, 12 ACCs, and 8 normal glands. The amplification status of HER-2/neu was also investigated by means of fluorescent in situ hybridization analysis on fixed material. The receptor tyrosine kinase (RTK)-deregulated profile of the SDCs was characterized by the overexpression of activated TRK-A in the presence of its ligand, and the overexpression of HER-2/neu sustained by gene amplification. The RTK signature of the ACCs was represented by the overexpression of activated KIT and TRK-A and their cognate ligands, and the overexpression of activated HER-2/neu, in the absence of gene amplification, possibly sustained by epidermal growth factor receptor heterodimerization. In conclusion, SDCs and ACCs, although sharing TRK-A autocrine loop activation, have different pathologically activated RTK-deregulated profiles that may be potential targets for pharmacological RTK inhibitors.
Insights
Salivary duct carcinomas (SDCs) and adenoid cystic carcinomas (ACCs) show distinct receptor tyrosine kinase (RTK) profiles. Understanding these molecular differences in SDCs and ACCs may lead to targeted therapies for these aggressive salivary gland cancers.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Salivary duct carcinomas (SDCs) and adenoid cystic carcinomas (ACCs) are aggressive salivary gland cancers with limited molecular characterization.
- Conventional treatments for SDCs and ACCs are often ineffective, highlighting the need for novel therapeutic strategies.
Purpose of the Study:
- To investigate the expression and activation status of key receptor tyrosine kinases (RTKs) including TRK-A, HER-2/neu, and KIT in SDCs and ACCs.
- To determine the presence of cognate ligands for these RTKs and assess HER-2/neu gene amplification in both cancer types.
Main Methods:
- Analysis of cryopreserved SDCs, ACCs, and normal salivary glands using immunoprecipitation, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR).
- Investigation of HER-2/neu amplification status via fluorescent in situ hybridization (FISH) on fixed tissue samples.
Main Results:
- SDCs exhibit overexpression of activated TRK-A with its ligand and HER-2/neu overexpression supported by gene amplification.
- ACCs show overexpression of activated KIT and TRK-A with their ligands, and activated HER-2/neu without gene amplification, potentially involving epidermal growth factor receptor (EGFR) heterodimerization.
Conclusions:
- SDCs and ACCs possess distinct pathologically activated RTK-deregulated profiles, despite a shared TRK-A autocrine loop activation.
- These identified RTK profiles represent potential therapeutic targets for novel pharmacological RTK inhibitors in salivary gland carcinomas.
