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KIT protein expression and analysis of c-kit gene mutation in adenoid cystic carcinoma
V A Holst1, C E Marshall, C A Moskaluk
1Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Abstract:
The c-kit proto-oncogene encodes a transmembrane receptor tyrosine kinase (KIT), which is expressed in several normal human tissues, especially mast cells and interstitial cells of Cajal. Expression of KIT has been noted in several types of neoplasms and gene mutation has been shown as a mechanism of c-kit oncogene activation in some tumors. Recently, a single adnexal adenoid cystic carcinoma (ACC) was reported to demonstrate KIT expression, however, examination of KIT expression or c-kit mutation in ACC of salivary glands has not been performed. We examined archival tissue samples from 30 ACC of major and minor salivary glands for KIT protein expression by immunohistochemistry with a polyclonal antibody and c-kit gene mutation by polymerase chain reaction amplification and DNA sequencing. KIT protein expression was noted in 90% of ACCs. An association between the presence of at least 50% KIT positive neoplastic cells and Grade 3 ACC or a solid growth pattern was observed (P < .05). KIT expression in normal or nonneoplastic salivary gland tissue was absent. No c-kit juxtamembrane domain (exon 11) or phosphotransferase domain (exon 17) mutations were found in any of the tumors examined. In conclusion, KIT protein expression is correlated with tumor grade of salivary ACC. However, gene mutation of exon 11 or exon 17 is not a mechanism of c-kit activation in these neoplasms.
Insights
KIT protein expression is common in salivary adenoid cystic carcinomas (ACCs), correlating with higher tumor grade. However, mutations in key c-kit gene regions were not found in these ACCs.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- The c-kit proto-oncogene encodes the KIT receptor tyrosine kinase, crucial in normal human tissues like mast cells.
- KIT expression is observed in various neoplasms, with mutations implicated in oncogene activation.
- Previous studies noted KIT expression in adnexal adenoid cystic carcinoma (ACC), but its role in salivary ACC remained unexamined.
Purpose of the Study:
- To investigate KIT protein expression and c-kit gene mutations in salivary gland adenoid cystic carcinomas (ACCs).
- To determine the correlation between KIT expression and clinicopathological features of ACCs, including tumor grade and growth pattern.
Main Methods:
- Archival tissue samples from 30 salivary ACCs were analyzed.
- KIT protein expression was assessed using immunohistochemistry.
- c-kit gene mutations in exons 11 and 17 were analyzed via polymerase chain reaction and DNA sequencing.
Main Results:
- KIT protein expression was detected in 90% of salivary ACCs.
- A significant association was found between high KIT expression (≥50% positive cells) and Grade 3 tumors or solid growth patterns (P < .05).
- No c-kit mutations in the juxtamembrane (exon 11) or phosphotransferase (exon 17) domains were identified in any examined tumors.
Conclusions:
- KIT protein expression is prevalent in salivary ACCs and correlates with tumor grade and morphology.
- c-kit gene mutations in exons 11 or 17 are not the mechanism driving c-kit activation in salivary ACCs.
- Further research may explore other oncogenic pathways in salivary ACC development.