TY - JOUR T1 - The Expression of FHIT in Salivary Carcinoma Ex Pleomorphic Adenoma JF - Anticancer Research JO - Anticancer Res SP - 3147 LP - 3152 VL - 32 IS - 8 AU - OMAR KUJAN AU - BASSEL TARAKJI AU - NALIN THAKKER AU - ABDUL AZIZ AL KHERAIF AU - PHILIP SLOAN Y1 - 2012/08/01 UR - http://ar.iiarjournals.org/content/32/8/3147.abstract N2 - 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. ER -