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. 2010 Dec 15;116(24):5749-56.
doi: 10.1002/cncr.25541. Epub 2010 Sep 7.

Cell type-dependent biomarker expression in adenoid cystic carcinoma: biologic and therapeutic implications

Diana Bell  1 , Dianna Roberts, Merrill Kies, Pulivarthi Rao, Randal S Weber, Adel K El-Naggar
Affiliations

Cell type-dependent biomarker expression in adenoid cystic carcinoma: biologic and therapeutic implications

Diana Bell et al. Cancer. .

Abstract

Background: Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by cellular, morphologic, and clinical heterogeneity. The authors of this report hypothesized that the dual cellular composition of ACC plays an important role in biomarker evaluation, tumor biologic behavior, and response to therapy.

Methods: To investigate the differential localization and expression of the c-Kit protein and the epidermal growth factor receptor (EGFR) protein, immunohistochemical analyses were performed on tissue arrays that were constructed from 199 tumors, and the results were correlated with clinicopathologic factors.

Results: c-Kit expression was limited to the inner ductal epithelial cells, whereas EGFR expression was limited mainly to the outer myoepithelial cells in the majority of ACCs with tubular and cribriform patterns. In solid ACCs, c-Kit uniformly was positive, whereas EGFR consistently was negative. A significant statistical correlation was observed between c-Kit expression and a poor 3-year outcome, and EGFR expression was correlated with a better 3-year outcome.

Conclusions: The current findings underscored the importance of cellular subtype localization of biomarkers in the clinical and therapeutic stratification of patients with ACC.

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Figures

Figure 1
Figure 1
H&E stained image of solid, tubular and cribriform adenoid cystic carcinoma. Strong c-kit immunopositivity (b) and no EGFR immunopositivity (c) and in a solid type ACC. Dual immunoreactivity for c-kit (ductal epithelial cells) (d) and EGFR (myoepithelial cells) (e) in tubular and cribriform type ACC.
Figure 2
Figure 2
Interphase in-situ hybridization of touch preparations of Adenoid Cystic Carcinoma c-kit containing BAC clone-RP11-586A2: normal (a) and increased copy number for c-kit copies (b –gain, c- amplification).
Figure 3
Figure 3
Overall survival plots for the three predominant patterns.
Figure 4
Figure 4
EGFR positivity in myoepithelial cells correlated with a better outcome.
See this image and copyright information in PMC

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