Abstract 3166: Clinopathologic correlation with the LCM based instability profiles for the mitochondrial microsatellite regions in the benign to metastatic transitions of surface epithelium ovarian tumor subtypes.
Authors: Alper Ozgul , Erdogan Gulgun , Pestereli Elif , Simsek Tayup , Caliskan Mualla O. , Gulkesen Hakan , Demir Durkadin , Görgişen Gökhan , Karaveli Seyda , Lüleci Güven 
Published: August 2014

Background: Up to date, genomic and microgenomic changes have been identified in nuclear genome whereas, there is no available data about the mitochondrial genome alterations in paired ovarian tumors. Additionally, genomic factors that involve in the progression to advanced stages of ovarian malignancy is still largely unknown. Current work suggest that the mitochondrial alterations have importance in the progress of carcinogenesis in spesific cell populations at clinical, pathological and molecular pathological levels.

Methods and Findings: We analyzed subtypes of 41 ovarian carcinoma samples including normal and tumor (benign, borderline and malignant) using laser captured microdissection technology. Out of 41 ovarian cases, 19 serous papillary carcinoma, 6 mucinous adenomcarcinoma, 9 endometrioid adenocarcinoma, 5 mixed type ovarian carcinoma, 1 undifferentiated carcinoma and 1 clear cell adenocarcinoma were included in the study. All samples were screened for 5.5kb (MT-D-Loop, MT-CytB, MT-ATPaz6-8, MT-12SrRNA, MT-16SrRNA) of mitochondrial genome by PCR-based sequencing analysis. A total of 91 variations were found. Sixty six percent (60/91) of these variations is shown in MITOMAP and 34% (31/91) is observed as novel variations. Overall, we did not find any correlation in D-Loop variations between pathological prognostic and molecular pathological prognostic factors (CD34,ER,PR,c-erbB-2,p53,MDR1,MDR3). However, the expression of a key component of drug resistance, protein GST (gluthatione S transferase), was detected as 270 in samples with instability; and 165 (median 25-75 percentile) in samples with stability in D-Loop position at 309 for C7TC6 repeats, (p&lt;0.05). Additionally, there was a significant difference in the mitotic index of Ki-67 expression in the samples whom had no changes in CA5 repeats as 37.2+20.00 and 54.3+17.0 in samples with CA5 repeat variations at position 514 (p&lt;0.05).

Conclusion: Our results suggest that our findings will add clinical value for the spesific/novel genetic variations detected in 34% of ovarian tumors. The results of microsatellite analysis in ovarian tumors showed changes of 26% for D310 (C)7-9, 37% for position 16184 (C)8-14. Our data supports the idea that, the variations spesifically in MT-D Loop and MT-CytB gene regions would reflect the preliminary transitional changes in progression of tumorigenesis. The functional use of LCM system and the microgenomic profiles will be definetely helpful for prognostic and therapeutic approaches in the field of mitochondrial oncology .

Citation Format: Ozgul Alper, Gulgun Erdogan, Elif Pestereli, Tayup Simsek, Mualla O. Caliskan, Hakan Gulkesen, Durkadin Demir, Gökhan Görgişen, Seyda Karaveli, Güven Lüleci. Clinopathologic correlation with the LCM based instability profiles for the mitochondrial microsatellite regions in the benign to metastatic transitions of surface epithelium ovarian tumor subtypes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3166. doi:10.1158/1538-7445.AM2013-3166