RT Journal Article SR Electronic T1 The Expression of FHIT in Salivary Carcinoma Ex Pleomorphic Adenoma JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3147 OP 3152 VO 32 IS 8 A1 OMAR KUJAN A1 BASSEL TARAKJI A1 NALIN THAKKER A1 ABDUL AZIZ AL KHERAIF A1 PHILIP SLOAN YR 2012 UL http://ar.iiarjournals.org/content/32/8/3147.abstract AB Background: Carcinoma ex-pleomorphic adenoma (Ca-ex-PA) is considered to be a malignant transformation product of pre-existing pleomorphic salivary adenoma (PSA). Aim: Our study aimed to characterise alterations in the immunohistochemical expression of the Fragile Histidine Traid (FHIT) and Cyclin-dependent Kinase Inhibitor 2A (CDKN2A) (p16INK4a) genes during tumour progression model from PSA to Ca-ex-PA in a cross sectional study. Materials and Methods: Paraffin blocks of 29 cases of PSA which were surrounded by normal parotid gland, and 26 cases of Ca-ex-PA were retrieved and validated. In all cases of Ca-ex-PA, a PSA ‘ghost’ was identified and the malignant element was either undifferentiated carcinoma or adenocarcinoma. Immunohistochemical staining and evaluation for CDKN2A and FHIT in 55 specimens were undertaken. Results: The results showed positive nuclear expression of p16 and FHIT in normal parotid gland. None (0%) of the PSA cases demonstrated loss of expression of nuclear FHIT, while 6/26 (23.1%) showed loss of FHIT express. Loss of CDKN2A expression was found in 12/29 (41.4%) of PSAs and 8/26 (30.8%) of Ca-ex-PAs. The nuclear expression pattern for FHIT was significantly more frequent in Ca-ex-PAs compared to PSAs (p=0.014). Conclusion: Our data suggest that inactivation of tumour suppressor genes plays an important role in the evolution of Ca-ex-PA. Furthermore, alteration of CDKN2A expression was found to be an early event in the malignant transformation of pleomorphic adenoma and could be considered as a target for gene therapy. More interestingly, we found that nuclear FHIT expression could be used as a good marker to distinguish PSA from Ca-ex-PA.