Cyst fluid hemoglobin species in endometriosis and its malignant transformation: The role of metallobiology

Abstract

Abstract. The aim of the present study was to assess the relative concentrations of hemoglobin (Hb) species in endometriosis as a possible indicator of malignancy. Electronic absorption spectroscopy was employed to quantify the Hb species present in the cyst fluid collected from 8 patients with endometriosis-associated ovarian cancer (EAOC), and compared with those present in the cyst fluid of 35 patients with benign endometriotic cysts. The 620/580 nm ratio in the electronic absorption spectrum, which was used as a surrogate indicator of the methemoglobin (metHb)/(oxyhemoglobin+metHb) ratio, was measured in each cyst fluid by ultraviolet/visible grating spectrophotometric microplate reader. The optimal cutoff value was defined according to the analysis of receiver operating characteristic (ROC) curve. The sensitivity and specificity of detection were calculated on the basis of the cutoff value to differentiate EAOC from endometriosis. The 620/580 nm ratio of cyst fluid in EAOC patients was much lower than that measured in women with benign cysts (0.389±0.266 vs. 0.666±0.188, P=0.021). ROC curve analysis performed using 0.35 as the optimal cutoff value indicated that the 620/580 nm ratio had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value of 62.5, 100.0, 100.0 and 92.1%, respectively, in the diagnosis of EAOC. In conclusion, metHb is one of the most abundant Hb species in benign cysts, and the absorption 620/580 nm ratio of cyst fluid exhibits high specificity and PPV as a surveillance test for the early detection of malignant transformation of endometriosis. Thus, metallobiology highlights diverse features involved in Hb homeostasis and the pathogenesis of malignant transformation of endometriosis.

Discrimination of malignant transformation from benign endometriosis using a near‑infrared approach

“…The present results were in agreement with those of Yoshimoto et al (6), who reported the cystic fluid concentration of total iron, heme iron, free iron and Hb species (6,7). Previous studies of Hb species have reported differences between OE and EAOC samples (8).…”

“…Furthermore, the cystic fluid Hb concentrations were reduced in patients with EAOC (6)(7)(8). The Δl values and total Hb concentrations in 46 samples exhibited an exponential correlation (r=0.558), suggesting that the Δl value may reflect the Hb concentration.…”

“…Cystic fluid total Hb concentrations were measured as described previously (6,8,13). From the correlation data, a formula was calculated to convert heme levels (mg/l) to hemoglobin (g/dl).…”

“…A recent ex vivo study revealed that electronic absorption spectroscopy using visible light at 580 and 620 nm provides a measure of Hb species in endometriotic cystic fluid by monitoring the relative concentrations of oxyhemoglobin and methemoglobin, respectively (8). The 620/580 nm peak ratio of cystic fluid in EAOC patients was significantly lower compared with that measured in women with benign OE (8). Therefore, the cystic fluid Hb species may be used as biomarkers in the differential diagnosis between EAOC and OE.…”

Endometriosis-associated ovarian cancer

“…Таким образом, под действием многих факторов развивается атипический эндометриоз, для которого характерны выраженные адгезивные и миграционные свойства, изменения в метаболизме эстрогенов и гор-мональных рецепторах, ферментная недостаточность с накоплением агрессивных метаболитов стероидов. Например, высокая ароматазная активность в очагах эндометриоза увеличивает превращение андростен-диона и тестостерона в эстрон и эстрадиол, а дефи-цит фермента 17β-гидроксистероид-дегидрогеназы (17β-ГСД) 2-го типа задерживает переход эстрадиола в эстрон, создавая длительную активацию рецепто-ров, усиливая пролиферацию клеток [15]. На фоне иммунологической дезорганизации и оксидативного повреждения, вызванного гемолизом эритроцитов, дополнительно развивается замедление апоптоза, что может быть одним из патогенетических факторов канцерогенеза.…”