RT Journal Article
SR Electronic
T1 DNA Damage Signaling and Apoptosis in Preinvasive Tubal Lesions of Ovarian Carcinoma
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 761
OP 769
DO 10.1097/IGC.0000000000000196
VO 25
IS 5
A1 Gautier Chene
A1 Veronique Ouellet
A1 Kurosh Rahimi
A1 Veronique Barres
A1 Katia Caceres
A1 Liliane Meunier
A1 Louis Cyr
A1 Manon De Ladurantaye
A1 Diane Provencher
A1 Anne Marie Mes Masson
YR 2015
UL http://ijgc.bmj.com/content/25/5/761.abstract
AB Objective High-grade serous ovarian cancer (HGSC) is the most life-threatening gynecological malignancy despite surgery and chemotherapy. A better understanding of the molecular basis of the preinvasive stages might be helpful in early detection and diagnosis. Genetic instability is 1 of the characteristics shared by most human cancers, and its level is variable through precancerous lesions to advanced cancer. Because DNA damage response (DDR) has been described as 1 of the first phases in genomic instability, we investigated the level of DDR activation and the apoptosis pathway in serous tubal intraepithelial carcinoma (STIC), the potential precursor of HGSC.Methods/Materials A tissue microarray including 21 benign fallopian tubes, 21 STICs, 17 HGSCs from patients with STICs (associated ovarian cancer [AOC]) from the same individuals, and 30 HGSCs without STICs (non-AOC) was used in this study.Immunohistochemistry was performed to evaluate the level of DDR proteins (pATM, pChk2, γH2AX, 53BP1, and TRF2), apoptosis proteins (Bcl2, BAX, and BIM), and cyclin E.Results The expression of all DDR proteins increased from benign fallopian tubes to STICs. The level of expression of pATM, pChk2, γH2AX, and TRF2 was also increased in STICs in comparison with AOC. BAX, BIM, and cyclin E expressions were high in STICs, whereas Bcl2 expression was low. Immunohistochemical profiles of AOC and non-AOC were also different.Conclusions These results suggest an activation of the DDR and apoptosis pathways in STICs, indicating that genomic instability may occur early in the precancerous lesions of HGSC.