| 21. |
- Hardell, Elin, et al.
(författare)
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Validation of a Mitotic Index Cutoff as a Prognostic Marker in Undifferentiated Uterine Sarcomas
- 2017
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Ingår i: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 41:9, s. 1231-1237
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Tidskriftsartikel (refereegranskat)abstract
- Undifferentiated uterine sarcomas (UUS) are a heterogenous group of high-grade mesenchymal tumors. Although these tumors are highly aggressive, a subset of patients may experience long-term survival. These tumors have previously been divided morphologically into uniform and pleomorphic types. A previous study demonstrated that a mitotic index cutoff of 25 mitoses/10 high-power fields (corresponding to 11.16 mitotic figures/mm) could successfully divide tumors into 2 prognostic groups with significantly different overall survival. The goals of the current study were to (1) validate this mitotic index cutoff in an independent, multicenter cohort and (2) explore the prognostic value of the mitotic index groups in relation to other clinicopathologic variables. Cases were included from 3 independent institutions: The Norwegian Radium Hospital, The Mayo Clinic, and Skåne University Hospital. A total of 40 tumors were included after central review. All cases were negative for the YWHAE-FAM22A/B and JAZF1-JJAZ1 translocations. Survival data were available on all patients. In this study, one-third of patients with UUS survived beyond 5 years. The crude (unadjusted) Cox Proportional Hazards model revealed a number of parameters that significantly impacted overall survival, including mitotic index group, patient age, stage, and the presence of tumor necrosis. Classification into the uniform and pleomorphic types was not prognostic. Combining these parameters into an adjusted model revealed that only the mitotic index group and stage were prognostic. On the basis of these findings, it is proposed that UUS be subdivided into “mitogenic” and “not otherwise specified” types.
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| 22. |
- Jönsson, Jenny-Maria, et al.
(författare)
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Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome.
- 2014
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 13:4, s. 537-545
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics.
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| 23. |
- Jönsson, Jenny Maria, et al.
(författare)
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Homologous recombination repair mechanisms in serous endometrial cancer
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Serous endometrial cancer (SEC) resembles high-grade serous ovarian cancer (HGSOC) genetically and clinically, with recurrent copy number alterations, TP53 mutations and a poor prognosis. Thus, SEC patients may benefit from targeted treatments used in HGSOC, e.g., PARP inhibitors. However, the preclinical and clinical knowledge about SEC is scarce, and the exact role of defective DNA repair in this tumor subgroup is largely unknown. We aimed to outline the prevalence of homologous recombination repair deficiency (HRD), copy-number alterations, and somatic mutations in SEC. OncoScan SNP arrays were applied to 19 tumors in a consecutive SEC series to calculate HRD scores and explore global copy-number profiles and genomic aberrations. Copy-number signatures were established and targeted sequencing of 27 HRD-associated genes was performed. All factors were examined in relation to HRD scores to investigate potential drivers of the HRD phenotype. Ten of the 19 SEC tumors (53%) had an HRD score > 42, considered to reflect an HRD phenotype. Higher HRD score was associated with loss of heterozygosity in key HRD genes, and copy-number signatures associated with non-BRCA1/2 dependent HRD in HGSOC. A high number of SECs display an HRD phenotype. It remains to be elucidated whether this also confers PARP inhibitor sensitivity.
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| 24. |
- Jönsson, Jenny-Maria, et al.
(författare)
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Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer.
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| 25. |
- Jönsson, Jenny-Maria, et al.
(författare)
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Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival.
- 2015
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Ingår i: Translational Oncology. - : Elsevier BV. - 1936-5233. ; 8:5, s. 424-433
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Tidskriftsartikel (refereegranskat)abstract
- Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival in epithelial ovarian cancer.
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| 26. |
- Lindahl, Bengt, et al.
(författare)
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Adenocarcinoma Corpus Uteri Stage I-II : Results of a Treatment Programme Based upon Cytometry
- 2009
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:11, s. 4731-4735
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Tidskriftsartikel (refereegranskat)abstract
- The results of a treatment method on adenocarcinoma corpus uteri stage I-II based upon cytometrically measured DNA ploidy are presented. All patients had a simple hysterectomy. Adjuvant treatment (postoperative vaginal brachytherapy) were given only, to those patients with non-diploid tumours regardless of stage and grade. A total of 1,634 women with endometroid adenocarcinoma corpus uteri stage I-II were included where 1,396 patients were followed-up for at least 5 years or until death and the remaining 238 patients were followed-up 3.5-5 years or until death. By using cytometry only, we identified a low-risk group comprising 83% of the patients (with 52% dead from their disease) and a high-risk group of 17% (with 15.7% dead from their disease). By using grade only (well- and moderately differentiated vs poorly differentiated), the low-risk group comprised 87% of the patients (with 4.6% dead from their disease) and the high-risk group 13% (with 13% dead from their disease). By using stage only (stage Ia and Ib vs stage Ic and II), the low-risk group comprised 78% of the patients (with 3.6% dead from their disease) and the high risk group 22% (with 14.5% dead from their disease). By combining these prognostic parameters, we were able to identify small subgroups with increased mortality rates in need of adjuvant therapy. As ploidy still had a strong prognostic strength regardless of given adjuvant radiotherapy, we do not believe that this treatment was effective. We therefore recommend future research to be directed toward cytostatics as an alternative adjuvant treatment.
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| 27. |
- Martin de la Fuente, Laura, et al.
(författare)
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Copy number signatures for early diagnosis of high-grade serous ovarian carcinoma
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe detection of ovarian carcinoma-derived somatic mutations in cervical samples and uterine lavages in several studies since 2013, has brought hope for the development of new biomarkers for early detection. High-grade serous ovarian carcinoma (HGSC) is strongly dominated by copy number alterations (CNAs). These CNAs are the consequence of underlying mutational processes in HGSC. We interrogated CNAs from low coverage whole-genome sequencing (WGS) data in HGSC tumors, plasma, endometrial biopsies, and cervical samples to explore if copy number signatures can be used as a biomarker for early detection of HGSC.Methods A total of 204 samples were included from 18 patients with HGSC, four BRCA mutation carriers and seven benign controls. Estimations of ploidy and cellularity, and thus calculation of absolute copy number, were optimized through a combination of the ACE, Rascal, and ichorCNA bioinformatic tools. Mixture modelling was used to subgroup the six fundamental copy number features and non-negative matrix factorization was used to generate the signatures and cluster the samples.ResultsWe extracted six fundamental copy number features from 69 diagnostic and pre-diagnostic cervical samples from patients diagnosed with HGSC and generated six CN signatures. We found different distributions of features in benign samples compared to tumors and cervical samples from HGSC patients. We also observed different exposures to the six signatures in different patient groups.ConclusionsFurther understanding of the components and cell types contributing to each signature, and inclusion of more cervical samples into the approach, will hopefully identify a novel tumorigenic signature for early detection of HGSC in cervical samples.
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| 28. |
- 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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| 29. |
- Måsbäck, Anna, et al.
(författare)
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Clinical and histopathological features of malignant melanoma in germline CDKN2A mutation families
- 2002
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Ingår i: Melanoma Research. - 0960-8931. ; 12:6, s. 549-557
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Tidskriftsartikel (refereegranskat)abstract
- Primary cutaneous malignant melanomas (CMMs) from 26 individuals belonging to nine families with an identified CDKN2A mutation were clinically and histopathologically compared with 78 matched CMM controls and with a population-based series of CMMs (n=667). All tumours were histopathologically re-examined. CDKN2A-associated cases were significantly less invasive compared with the matched controls, with an adjusted odds ratio (adjOR) of 2.9 and a 95% confidence interval (CI) of 1.0-8.1 (P=0.04). According to the odds ratio (OR) values, CDKN2A-associated cases seemed to have tumours more often located on the head and neck (adjOR 2.9, 95% CI 0.6-13.7), with less inflammation (adjOR 0.7, 95% CI 0.3-1.8) and regression (adjOR 0.6, 95% CI 0.2-1.8) but more frequent histological ulceration (adjOR 1.9, 95% CI 0.6-5.8). In comparison with the population-based material, CDKN2A-associated cases were significantly younger at diagnosis (crude OR 3.5, 95% CI 1.6-7.5, divided at 50 years) and had less regressive reaction in their tumours (crude OR 0.355 95% CI 0.2-0.8). No significant differences were seen for tumour thickness between the different groups. On multivariate analysis, the overall survival was significantly worse for thicker tumours and older age (P=0.04 for both). To our knowledge this is the first description of the histopathological features of CMMs from families with mutations in the CDKN2A gene.
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| 30. |
- Måsbäck, Anna, et al.
(författare)
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Cutaneous malignant melanoma in South Sweden 1965, 1975, and 1985. A histopathologic review
- 1994
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Ingår i: Cancer. - 0008-543X. ; 73:6, s. 1625-1630
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is an increase in the incidence of cutaneous malignant melanoma (CMM) among white people throughout the world. In Sweden, a fivefold increase has been recorded since 1960, but the mortality is rising at a much lower rate. Tumor thickness is the single most important prognostic factor for primary melanoma. This study aimed to clarify whether the thickness of the tumor in invasive CMM decreased during the period 1965–1985. Methods. This population‐based study identified 574 cases of CMM, both invasive and noninvasive, in the South Swedish Health Care Region in 1965, 1975, and 1985. Twenty‐six cases were excluded because the collection or evaluation of the material was not possible. The remaining 548 cases were reviewed histopathologically, and a diagnosis of invasive CMM was rejected in 71 cases. Eventually, 467 cases of invasive melanoma remained in our study (70 in 1965, 124 in 1975, and 273 in 1985). The level of invasion, tumor thickness, regression, ulceration, presence of inflammatory cells, benign naevus cells, and the site of presentation were studied. Results. The study found neither a significant decrease of tumor thickness of invasive CMM nor changes in the level of invasion or proportion of ulcerated melanoma. A significantly higher proportion of melanoma tumors containing benign naevus cells was seen throughout the years (P < 0.05). Women had significantly fewer inflammatory cells in their tumors than did men (P < 0.01). As expected, the anatomical site of presentation showed a significant sex‐related difference, with more tumors on the legs of female patients and more on the trunk of male patients (P < 0.001). Conclusions. There is a divergence between the rapidly increasing incidence and the slower increase in mortality of CMM. This cannot be explained by a removal of the melanoma at a thinner thickness. Differences between the sexes according to the tumor site and the increasing rate of CMM containing benign naevus cells could implicate changes in the tumor biology. Public education in Sweden concerning ultraviolet radiation and the connection with melanoma is fairly new and might not have any influence on this time period. Additional investigation is needed to clarify this matter.
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