Kit protein expression and analysis of c-kit gene mutation in Adenoid Cystic Carcinoma

Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Modern Pathology (Impact Factor: 6.19). 11/1999; 12(10):956-60.
Source: PubMed


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.

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    • "The relationship between high c-KIT expression (>50%) and histologic grade is debated. While Holst et al. [51] noted a significant association of c-KIT expression with grade III or solid pattern AdCC, Freier et al. [52] described a high expression only in cribriform and tubular AdCC. Limited amounts of VEGF-C are produced in AdCC, which via a reduced interaction with VEGFR-3 may result in few lymphatic vessels; whether this relates to the purported low rate of cervical metastasis remains to be evaluated [53]. "
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    ABSTRACT: This article provides an update on the current understanding of adenoid cystic carcinoma of the head and neck, including a review of its epidemiology, clinical behavior, pathology, molecular biology, diagnostic workup, treatment and prognosis. Adenoid cystic carcinoma is an uncommon salivary gland tumor that may arise in a wide variety of anatomical sites in the head and neck, often with an advanced stage at diagnosis. The clinical course is characterized by very late recurrences; consequently, clinical follow-up should extend at least >15years. The optimal treatment is generally considered to be surgery with postoperative radiotherapy to optimize local disease control. Much effort has been invested into understanding the tumor's molecular biological processes, aiming to identify patients at high risk of recurrence, in hopes that they could benefit from other, still unproven treatment modalities such as chemotherapy or biological therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.
    05/2015; 51(7). DOI:10.1016/j.oraloncology.2015.04.005
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    • "Therefore, it has been established that c-kit protein overexpression, rather than mutation, is involved in the pathogenesis of ACC. To date, no gene mutation has been clearly identified as the mechanism of c-kit activation in this neoplasm [42-44]. Seven studies have assessed imatinib in over 80 advanced ACC (7 studies have used imatinib alone, and one study has evaluated the association imatinib/cisplatin), with only 4 partial responses, for an objective response rate of 5% [49-56]. "
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    ABSTRACT: Salivary gland cancers are very rare tumors. They are characterized by a histologic heterogeneity and a poor outcome. According to this rarity, few prospective data are available to date. No standard recommendations could be held for the use of systemic therapy in these tumors. Several case reports and small studies have investigated the contribution of different agents of chemotherapy. With the extension of molecular biology approach in oncology several signaling pathways have been discovered in different cancers including salivary gland cancers; thus a number of targeted therapies have been investigated. This paper reviewed exhaustively the studies investigating the role of systemic therapies (chemotherapy, targeted therapy, hormone therapy) in salivary gland cancers.
    Head & Neck Oncology 05/2012; 4(1):19. DOI:10.1186/1758-3284-4-19 · 3.14 Impact Factor
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    • "Ro et al. applied the same grading system to ACCs from both types of tissues, and both breast and salivary gland tumors are characterized by expression of c-KIT and share a common chromosomal translocation t(6;9) leading to the fusion gene MYB-NFIB (Marchio et al., 2010; Persson et al., 2009; Ro et al., 1987). c-KIT has been shown to be expressed in 80– 100% of ACCs of the salivary glands and in almost all ACCs from the breast (Azoulay et al., 2005; Crisi et al., 2005; Edwards et al., 2003; Holst et al., 1999; Jeng et al., 2000; Mastropasqua et al., 2005; Vila et al., 2009; Weigelt et al., 2008). The genetic alteration t(6;9)(q22-23;p23-24) was first identified as a characteristic of salivary gland ACCs (Nordkvist et al., 1994). "

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