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Abstract

BackgroundA majority of primary ovarian neoplasms arise from cell surface epithelium of the ovaries. Although old age and a positive family history are associated risk factors, the etiology of the epithelial ovarian tumors is not completely understood. Additionally, knowledge of factors involved in the histogenesis of the various subtypes of this tumor as well as those factors that promote progression to advanced stages of ovarian malignancy are largely unknown. Current evidence suggests that mitochondrial alterations involved in cellular signaling pathways may be associated with tumorigenesis.MethodsIn this study, we determined the presence of polymorphisms and other sequence variants of mitochondrial DNA (mtDNA) in 102 epithelial ovarian tumors including 10 matched normal tissues that paired with some of the tumors. High-resolution restriction endonucleases and PCR-based sequencing were used to assess the mtDNA variants spanning 3.3 kb fragment that comprised the D-Loop and 12S rRNA-tRNAphe, tRNAval, tRNAser, tRNAasp, tRNAlys, ATPase 6, ATPase 8, cytochrome oxidase I and II genes.ResultsThree hundred and fifty-two (352) mtDNA sequence variants were identified, of which 238 of 352 (68%) have not been previously reported. There were relatively high frequencies of three mutations in the 12S rRNA gene at np 772, 773, and 780 in stage IIIC endometrioid tumors, two of which are novel (773delT and 780delC), and occurred with a frequency of 100% (7/7). Furthermore, two mutations were observed in serous tumors only at np 1657 in stage IV (10/10), and at np 8221delA in benign cystadenomas (3/3) and borderline tumors (4/4). A high frequency, 81% (13/16) of TC insertion at np 310 was found only in early stages of serous subtype (benign cystadenomas, 3/3; borderline tumors, 4/4; stage I tumors, 2/5 and matched normal tissues 4/4).ConclusionOur findings indicate that certain mtDNA mutations can reliably distinguish the different histologic subtypes of epithelial ovarian tumors. In addition, these data raise the possibility that certain mtDNA mutations may be useful biomarkers for predicting tumor aggressiveness and may play a potential role in tumorigenesis.

Reactive Oxygen Species and Serous Epithelial Ovarian Adenocarcinoma

“…This arises because of the difficulties in accessing ovarian tissues and other anatomical histology appearances. Given that early stage ovarian cancer has a greater five year survival status than advanced presentation, the difficulty lies in the detection of early malignant or premalignant changes in the ovaries [1, 3]. ROS are short lived oxygen-containing derivatives developed as by-products of normal cellular respiration that help to maintain cellular homeostasis along with the body’s innate antioxidant system [1,16].…”

“…Further, oxidative stress has been associated with the promotion of many human diseases including various cancers [1, 2, 16, 17, 18]. Specifically, ovarian tumors have known to secrete excessive amounts of ROS leading to increase tumor size [3, 11]. Moreover, the microenvironment generated as a result of oxidative injury may help the compounds evade normal checkpoints to trigger human disease [22].…”

“…Ovarian cancer represents the fifth most frequent cause of cancer mortality among American women, and is by far the most aggressive form of malignancy affecting the female reproductive tract [1–3]. Interestingly, African-American women (AA) carry the heaviest mortality from the disease compared to their Caucasian counterparts, though the cause for the inequality is relatively unclear [4].…”

“…Furthermore, the etiology of serous ovarian cancer (SOC) and its’ progression is not fully understood, but could be attributed to genetic instability induced by inflammation resulting from repeated repair of ovulatory defects in the epithelium lining the ovaries and fallopian tubes [5]. Multiple studies have reported release of reactive oxygen species (ROS) at the inflammatory site could damage DNA, proteins, and lipids leading to an array of cancers [1, 3, 5]. The major adverse effect of ROS is increased oxidative stress resulting from an overproduction of reactive compounds, antioxidants exhaustion, or both.…”

Effect of estrogen receptor β agonists on proliferation and gene expression of ovarian cancer cells

“…Due to missing screening methods and its aggressive behaviour, a vast number is diagnosed at an advanced stage [2]. Steroid hormones have an influence on ovarian cancer cells [3] and it has been shown that 40–60% of ovarian cancers express estrogen receptor (ER) α [4, 5].…”