Differential Expression of CyclinD1 and p16INK4A in Benign and Malignant Salivary Gland Tumors: A Study of 44 Cases
George Jour, Kamille West, Violette Ghali, Georges Ephrem, Bruce Wenig. BIMC, New York, NY
Background: Salivary gland tumors comprise a morphologically and biologically diverse group of lesions.There is conflicting data concerning the molecular events involving the pRb pathway in these tumors.Recent studies suggest that promoter hypermethylation or homozygous deletion of p16INK4a gene in adenoid cystic carcinomas(AdCC) and mucoepidermoid carcinomas (MEC) are the most common mechanisms for p16INK4Asilencing. Few studies examined the alterations in the Rb pathway by immunohistochemical (IHC) methods in benign and malignant salivary gland tumors. Furthermore, recent evidence implicates HPV in MEC carcinogenesis.The purpose of our study is to examine p16INK4A and cyclin D1 expression in a variety of benign and malignant salivary gland tumors, and to investigate p16 expression as a surrogate marker for HPV infection in MEC.
Design: 44 cases were selected from the Pathology files in our hospital centers. The series includes 31 malignant tumors (14 MEC, 5 acinic cell carcinomas (ACC), 5 polymorphous low grade adenocarcinomas (PLGA), 6 (AdCC) and 14 benign tumors (4 benign cysts, 5 Warthin tumors and 5 pleomorphic adenomas (PA). All cases were tested by IHC for p16INK4A and Cyclin D1. Testing for HPV wide spectrum (HPV-WS) was performed by in situ hybridization in all MEC cases. Staining intensity was recorded semi quantitatively (on a scale from 0 to 4+). Fisher's exact test and correlation with a p <0.05 were used to assess the differences and correlation in frequencies of various parameters tested.
Results: Cyclin D1 and p16 are expressed similarly in malignant and benign tumors (p=0.126 and p =0.464, respectively).None of the MEC cases showed nuclear reactivity for HPV-WS. Statistical analysis showed positive correlation between Cyclin D1 and p16 expression.
Conclusions: 1) CyclinD1 and p16INK4A are overexpressed in both malignant and benign salivary gland tumors but not within the normal salivary gland epithelium; the lack of statistical difference between the two groups suggests that these deregulations are unrelated to their biological behavior; 2) The absence of nuclear reactivity for HPV-WS in all MEC cases suggests that p16 overexpression in these tumors cannot be used as a surrogate marker for viral infection; 3) The positive correlation between CCND1 and p16INK4A suggests that CyclinD1 gene over expression may represent a priamry tumorigenic event in salivary gland neoplasms leading to secondary p16INK4A over expression by an ineffective positive feedback mechanism, similar to that seen in HPV infection. Further molecular studies targeting the CyclinD1 gene locus are warranted.
Category: Head & Neck
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 162, Tuesday Afternoon