Adenosquamous Carcinomas of the Head and Neck: An Analysis of MDM2, p53 Expression and MAML2 Rearrangements
RR Seethala, X Zhang, S Turner, K Cieply, R Tubbs, S Dacic, JL Hunt. University of Pittsburgh, Pittsburgh, PA; Cleveland Clinic, Cleveland, OH
Background: Adenosquamous carcinoma (AsqCA), though generally considered a variant of squamous cell carcinoma (SCC), shows considerable morphologic overlap with mucoepidermoid carcinoma (MEC). To date, the question of whether the molecular alterations in AsqCA resemble those of conventional SCC or those of MEC has not been addressed. We describe our survey of AsqCA with markers that represent key molecular pathways of MEC (MAML2 rearrangement), and conventional SCC (MDM2 TP53), respectively.
Design: Twenty cases of AsqCA were selected for immunohistochemical (IHC) analysis and fluorescent in-situ hybridization (FISH). Anti-p53 (1:100, clone DO-7, Dako, Carpinteria, CA) and anti-MDM2 (1:50, clone IF2, Invitrogen, Carlsbad, CA) staining was visualized using a brown (DAB) chromogen. Only strong staining in greater than 25% of nuclei was considered positive. FISH analysis was performed as follows: TP53 - SpectrumGreen-labelled CEP17 and SpectrumOrange-labeled 17p13.1 (TP53) probes (Vysis, Downers, IL); MDM2 - SpectrumGreen-labeled CEP12 (Abbott Molecular, DesPlaines, IL) and SpectrumOrange-labeled BAC probe (RP11-775J10 and RP11-450G15 12q15, Roswell Park Cancer Institute, Buffalo, NY); MAML2 - 11q21 break apart probe (SpectrumGreen-labeled BAC probe RP11-676L3 and SpectrumOrange-labeled BAC probe RP11-16K5 spanning MAML2, Childrens Hospital Oakland Research Institute). A heterozygous deletion of TP53 was defined as loss in >20% of diploid cells. Amplification of MDM2 was defined as a MDM2:CEP12 ratio of >2.0. Positivity for MAML2 rearrangement was defined as split signal in >20%.
Results: 63% (10/16) AsqCA were p53 IHC positive, while only 14% (2/14) were MDM2 IHC positive. 52% (9/17) showed loss of TP53 by FISH while 15% (3/20) showed MDM2 gene amplification. 75% (6/8) cases with TP53 loss were p53 IHC positive, though 50% (4/8) TP53 intact cases were also p53 IHC positive. Only one of two MDM2 immunopositive cases showed amplification. None of the MDM2 amplified cases showed TP53 loss. None of the AsqCA tested (n=12) showed MAML2 rearrangements.
Conclusions: As suggested by clinical and histologic criteria, AsqCA appears to be fundamentally different from MEC at a molecular level as well. They share the high prevalence of p53 alterations seen in conventional SCC. The finding of MDM2 gene amplification, though rare in AsqCA, is novel, and to date, undescribed in any variant of head and neck SCC.
Category: Head & Neck
Tuesday, March 10, 2009 1:15 PM
Platform Session: Section H, Tuesday Afternoon