| 1. |
- Bååth, Maria, et al.
(författare)
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SOX2 is a promising predictor of relapse and death in advanced stage high-grade serous ovarian cancer patients with residual disease after debulking surgery
- 2020
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Ingår i: Molecular and Cellular Oncology. - : Informa UK Limited. - 2372-3556. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor SOX2 is a well-established and important stem cell marker. Its role in cancer biology remains unclear, but it has been proposed to also be a marker of cancer stem cells. We investigated the role of SOX2 protein expression in women with high-grade serous ovarian cancer (HGSOC) to determine its potential prognostic and treatment predictive value. We constructed a tissue microarray of 130 advanced stage HGSOC tumors with an average of 6 cores each, stained for SOX2 protein expression and evaluated survival outcomes. We also treated two HGSOC cell lines with carboplatin and paclitaxel and measured SOX2 expression by RT-PCR and immunoblotting at different doses and time-points. Among patients with non-radical debulking surgery overall and progression-free survival were shorter for patients with SOX2 positive tumors (mean 26 vs. 39 months, log-rank test: p = .0076, and mean 14 vs. 19 months, p = .055, respectively). Knockdown of SOX2 in cell lines did not affect growth inhibition following chemotherapy treatment. Our results show that SOX2 has a strong prognostic potential among HGSOC patients with residual tumor tissue after debulking surgery and suggest that SOX2 expressing cells remaining after non-radical debulking surgery may constitute a subpopulation of cancer stem cells with greater tumor-initiating potential.
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| 2. |
- Martin de la Fuente, Laura, et al.
(författare)
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PD-1/PD-L1 expression and tumor-infiltrating lymphocytes are prognostically favorable in advanced high-grade serous ovarian carcinoma
- 2020
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Ingår i: Virchows Archiv: an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 477:1, s. 83-91
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Tidskriftsartikel (refereegranskat)abstract
- The response rate to checkpoint inhibitors for women with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is modest, and development of predictive biomarkers is needed. The main focus has been on tumor cell PD-L1 expression, but its assessment alone is insufficient for patient selection in most malignancies. We mapped the presence of macrophages (CD68 and CD163) and lymphocytes (CD3) located within the tumor epithelium, the cell type-specific expression of PD-L1 and PD-1, and their impact on 5-year overall survival (OS) in a consecutive cohort of 130 women diagnosed with advanced HGSC between 2011 and 2015. PD-L1 was expressed mainly by macrophages (not by tumor cells) and PD-1 by lymphocytes. Women with higher CD3, PD-L1, and PD-1 expression had improved OS (P = 0.03, P = 0.007, and P = 0.02, respectively). In the external data set (203 women), high expression of CD274 (encoding PD-L1) was associated with improved OS (P = 0.03), in accordance with our results. Furthermore, higher CD163 expression was associated with better outcome in women with no residual tumor after primary surgery (P = 0.02). Thus, women with greater lymphocyte tumor infiltration had better outcome and PD-L1/PD-1 expression, regardless of PD-1/PD-L1 being markers for immune suppressive pathways, conferred a survival benefit in our cohort. Our results highlight that tumor immunity may be harnessed in subsets of HGSC.
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| 3. |
- Sartor, Hanna, et al.
(författare)
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Ovarian cancer subtypes and survival in relation to three comprehensive imaging parameters
- 2020
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Ingår i: Journal of Ovarian Research. - : Springer Science and Business Media LLC. - 1757-2215. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ovarian cancer (OC) is usually detected in late clinical stages, and imaging at diagnosis is crucial. Peritoneal carcinomatosis (PC) and cardio phrenic lymph nodes (CPLN) are pathological findings of computed tomography (CT) and are relevant for surgical planning. Furthermore, mammographic breast density (BD) has shown an association with OC risk and might be prognostically relevant. However, it is not known if PC, CPLN, and BD are associated with aggressive OC subtypes and impaired OC survival. Herein, we investigated associations between three comprehensive image parameters and OC subtypes and survival. Methods: The Malmö Diet and Cancer Study is a prospective study that included 17,035 women (1991-1996). Tumor information on 159 OC and information on OC specific survival (last follow-up, 2017-12-31) was registered. The CT and mammography closest to diagnosis were evaluated (Peritoneal Carcinomatosis Index PCI, CPLN, and BD). Associations between CT-PCI, CPLN, and BD vs. clinical stage [stage I vs. advanced stage (II-IV), histological type/grade (high grade serous and endometrioid vs. other subtypes], and OC-specific survival were analyzed by logistic and Cox regression. Results: There was a significant association between higher CT-PCI score and advanced clinical stage (adjusted OR 1.26 (1.07-1.49)), adjusted for age at diagnosis and histological type/grade. Increasing CT-PCI was significantly associated with impaired OC specific survival (adjusted HR 1.04 (1.01-1.07)), adjusted for age at diagnosis, histological type/grade, and clinical stage. There was no significant association between PCI and histological type/grade, nor between BD or CPLN vs. the studied outcomes. Conclusions: Image PCI score was significantly associated with advanced clinical stages and impaired OC survival. An objective approach (based on imaging) to scoring peritoneal carcinomatosis in ovarian cancer could help surgeons and oncologists to optimize surgical planning, treatment, and care.
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