Primary and metastatic ovarian cancer: Characterization by 3.0T diffusion-weighted MRI

Lindgren, Auni; Anttila, Markku; Rautiainen, Suvi; Arponen, Otso; Kivelä, Annukka M.; Mäkinen, Petri; Härmä, Kirsi Hannele; Hämäläinen, Kirsi; Kosma, Veli‐Matti; Ylä‐Herttuala, Seppo; Vanninen, Ritva; Sallinen, Hanna

doi:10.1007/s00330-017-4786-z

Cited by 32 publications

(21 citation statements)

References 33 publications

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“…Recent studies and meta‐analyses have shown a strong correlation between ADC and cellularity and a good association between ADC and cell proliferation (in terms of KI67 nuclear protein) in ovarian cancer, mainly of the serous subtype . In agreement with studies on other tumor types, our results show that response to treatment is clearly identified using mono‐exponential fitting with b values higher than 100 s/mm 2 .…”

Section: Discussionsupporting

confidence: 89%

Integration of MRI and MRS approaches to monitor molecular imaging and metabolomic effects of trabectedin on a preclinical ovarian cancer model

et al. 2018

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Although several drugs are available to treat recurrences of human epithelial ovarian cancer (EOC), clinical responses often remain short lived and lead to only marginal improvements in patients' survival. One of the new drugs proposed for recurrent platinum-resistant EOC patients is trabectedin (Trab), a marine-derived antitumor agent initially isolated from the tunicate Ecteinascidia turbinata and currently produced synthetically. Predictive biomarkers of therapy response to this drug and the potential use of non-invasive functional MRI and MRS approaches for an early assessment of Trab efficacy have not yet been evaluated, although they might be relevant for improving the clinical management of EOC patients. In the present work we combined functional and spectroscopic magnetic resonance technologies, such as in vivo diffusion-weighted MRI and 1 H MRS, with ex vivo high resolution MRS (HR-MRS) metabolomic analyses, with the aim of identifying new pharmacodynamic markers of Trab effectiveness on well characterized, highly aggressive human SKOV3.ip (a HER2-enriched cell variant derived from SKOV3 cells) EOC xenografts. In vivo treatment with Trab (three consecutive weekly 0.2 mg/kg i.v. injections) resulted in the following: (1) a significant reduction of in vivo tumor growth, along with the formation in cancer lesions of diffuse hyper-intense areas detected by T 2 -weighted MRI and attributed to necrosis, in agreement with histopathology findings; (2) significant increases in the apparent diffusion coefficient mean and median values versus saline-treated control tumors; and (3) a significant reduction in the cholinecontaining metabolites' signal detected by quantitative in vivo MRS. Multivariate and quantitative HR-MRS analyses on ex vivo tissue samples revealed Trab-induced alterations in phospholipid and glucose metabolism identified as a decrease in phosphocholine and an increase in lactate. Collectively, these data identify Trab-

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Section: Discussionsupporting

confidence: 89%

Integration of MRI and MRS approaches to monitor molecular imaging and metabolomic effects of trabectedin on a preclinical ovarian cancer model

et al. 2018

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“…Tissue samples were embedded in paraffin and cut into 5-μm-thick sections. Next, the sections were processed for staining with hematoxylin-eosin, VEGF-A (1:250; Santa Cruz), VEGF-C (1:20; Novus), VEGF-D (1:20; Santa Cruz), VEGFR1 (1:15; Santa Cruz), VEGFR2 (1:750; Cell Signaling), and VEGFR3 (11:000, Millipore/Chemicon) [21–25].…”

Section: Methodsmentioning

confidence: 99%

Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer

et al. 2019

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Background In many malignancies including ovarian cancer, different angiogenic factors have been related to poor prognosis. However, data on their relations to each other or importance as a prognostic factor in ovarian cancer is missing. Therefore, we investigated the expressions of VEGF-A, VEGF-C, and VEGF-D, and the receptors VEGFR1, VEGFR2, and VEGFR3 in patients with malignant epithelial ovarian neoplasms. We further compared expression levels between primary tumors and related distant omental metastases. Methods This study included 86 patients with malignant ovarian epithelial tumors and 16 related distant metastases. Angiogenic factor expression was evaluated using immunohistochemistry ( n = 102) and qRT-PCR ( n = 29). Results Compared to primary high grade serous ovarian tumors, the related omental metastases showed higher expressions of VEGF-A ( p = 0.022), VEGF-D ( p = 0.010), and VEGFR1 ( p = 0.046). In univariate survival analysis, low epithelial expression of VEGF-A in primary tumors was associated with poor prognosis ( p = 0.024), and short progression-free survival was associated with high VEGF-C ( p = 0.034) and low VEGFR3 ( p = 0.002). The relative expressions of VEGF-D, VEGFR1, VEGFR2, and VEGFR3 mRNA determined by qRT-PCR analyses were significantly correlated with the immunohistochemically detected levels of these proteins in primary high grade serous ovarian cancer and metastases ( p = 0.004, p = 0.009, p = 0.015, and p = 0.018, respectively). Conclusions The expressions of VEGF receptors and their ligands significantly differed between malignant ovarian tumors and paired distant metastases. VEGF-A, VEGF-D, and VEGFR1 protein expressions seem to be higher in distant metastases than in the primary high grade serous ovarian cancer lesions.

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“…A possible explanation may be that cancer nests with extremely low ADC values have the potential for rapid and aggressive cancer growth. Consistent with this idea, a close relationship was found between low ADC values and expression levels of Ki-67 protein, which is considered a molecular marker of accelerated cell proliferation [ 20 , 21 ]. Furthermore, a high level of Ki-67 protein expression was reportedly associated with high mortality of patients with various subtypes of salivary gland carcinomas [ 16 , 22 ].…”

Section: Discussionmentioning

confidence: 75%

Salivary gland carcinoma: Prediction of cancer death risk based on apparent diffusion coefficient histogram profiles

Sumi

Nakamura

2018

PLoS ONE

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We evaluated apparent diffusion coefficient (ADC) histogram parameters for predicting the outcomes of patients with salivary gland carcinoma. Diffusion-weighted MR imaging was performed in 20 patients with salivary gland carcinoma, and ADCs were determined using b-values of 500 and 1000 s/mm2. ADC histogram parameters (mean, median, percentage tumor area with distinctive ADC values [pADC], skewness, and kurtosis) were analyzed. The patients were followed for 5–136 months after primary surgery. The ADC histogram parameters and T (pT), N(pN), and M categories of the primary tumors were assessed for the prognostic importance using Cox proportional hazards models, logistic regression analysis, and receiver operating characteristic (ROC) analysis. Cohen’s d was determined for evaluating the importance of differences in the parameters between two patient groups with different outcomes. Six patients died of cancer (DOC) within 3 years after the primary surgery. Cox proportional hazards models indicated that ADC mean (95% CI = 0.494–0.977, p = 0.034), ADC median (95% CI = 0.511–0.997, p = 0.048), pADC with extremely low (<0.6 mm2/s) ADC (95% CI = 1.013–1.082, p = 0.007), kurtosis (95% CI = 1.166–7.420, p = 0.023), and pN classification (95% CI = 1.196–4.836, p = 0.012) were important factors of cancer death risk. ROC analyses indicated that the pADC <0.6 ×10−3 mm2/s was the best prognostic predictor (p <0.001; AUC = 0.929) among the ADC and TNM classification parameters that were significant in a univariate logistic regression analysis. Cohen’s d values between the DOC and survived patients for the ADC mean, ADC median, pADC with extremely low ADC, and kurtosis were 1.06, 1.04, 2.12, and 1.13, respectively. These results suggest that ADC histogram analysis may be helpful for predicting the outcomes of patients with salivary gland carcinoma.

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Primary and metastatic ovarian cancer: Characterization by 3.0T diffusion-weighted MRI

Cited by 32 publications

References 33 publications

Integration of MRI and MRS approaches to monitor molecular imaging and metabolomic effects of trabectedin on a preclinical ovarian cancer model

Integration of MRI and MRS approaches to monitor molecular imaging and metabolomic effects of trabectedin on a preclinical ovarian cancer model

Expression profiles of VEGF-A, VEGF-D and VEGFR1 are higher in distant metastases than in matched primary high grade epithelial ovarian cancer

Salivary gland carcinoma: Prediction of cancer death risk based on apparent diffusion coefficient histogram profiles

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