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  • Epstein, Elisabeth, et al. (författare)
  • Early-stage cervical cancer: Tumor delineation by magnetic resonance imaging and ultrasound - A European multicenter trial
  • 2013
  • Ingår i: Gynecologic Oncology. - : Academic Press. - 1095-6859. ; 128:3, s. 449-453
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in the preoperative assessment of early-stage cervical cancer using pathologic findings as the reference standard. Patients and methods. Prospective multi-center trial enrolling 209 consecutive women with early-stage cervical cancer (FIGO IA2-IIA) scheduled for surgery. The following parameters were assessed on US and MRI and compared to pathology: remaining tumor, size, tumor stromal invasion <2/3 (superficial) or >= 2/3 (deep), and parametrial invasion. Results. Complete data were available for 182 patients. The agreement between US and pathology was excellent for detecting tumors, correctly classifying bulky tumors (>4 cm), and detecting deep stromal invasion (kappa values 0.84, 0.82, and 0.81 respectively); and good for classifying small tumors (<2 cm) and detecting parametrial invasion (kappa values 0.78 and 0.75, respectively). The agreement between MRI and histology was good for classifying tumors as <2 cm, or >4 cm, and detecting deep stromal invasion (kappa values 0.71, 0.76, and 0.77, respectively). It was Moderately accurate in tumor detection, and in assessing parametrial invasion (kappa values 0.52 and 0.45, respectively). The agreement between histology and US was significantly better in assessing residual tumor (p<0.001) and parametrial invasion (p<0.001) than the results obtained by MRI. Imaging methods were not significantly influenced by previous cone biopsy. Conclusion. US and MRI are highly accurate for the preoperative assessment of women with early-stage cervical cancer, although US may be more accurate in detecting residual tumors and assessing parametrial invasion. (C) 2012 Elsevier Inc. All rights reserved.
  • Binzer-Panchal, Amrei, et al. (författare)
  • Integrated molecular analysis of undifferentiated uterine sarcomas reveals clinically relevant molecular subtypes
  • 2019
  • Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 25:7, s. 2155-2165
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Undifferentiated uterine sarcomas (UUS) are rare, extremely deadly, sarcomas with no effective treatment. The goal of this study was to identify novel intrinsic molecular UUS subtypes using integrated clinical, histopathologic, and molecular evaluation of a large, fully annotated, patient cohort. Experimental Design: Fifty cases of UUS with full clinicopathologic annotation were analyzed for gene expression (n ¼ 50), copy-number variation (CNV, n ¼ 40), cell morphometry (n ¼ 39), and protein expression (n ¼ 22). Gene ontology and network enrichment analysis were used to relate over- and underexpressed genes to pathways and further to clinicopathologic and phenotypic findings. Results: Gene expression identified four distinct groups of tumors, which varied in their clinicopathologic parameters. Gene ontology analysis revealed differential activation of pathways related to genital tract development, extracellular matrix (ECM), muscle function, and proliferation. A multi-variable, adjusted Cox proportional hazard model demonstrated that RNA group, mitotic index, and hormone receptor expression influence patient overall survival (OS). CNV arrays revealed characteristic chromosomal changes for each group. Morphometry demonstrated that the ECM group, the most aggressive, exhibited a decreased cell density and increased nuclear area. A cell density cutoff of 4,300 tumor cells per mm 2 could separate ECM tumors from the remaining cases with a sensitivity of 83% and a specificity of 94%. IHC staining of MMP-14, Collagens 1 and 6, and Fibronectin proteins revealed differential expression of these ECM-related proteins, identifying potential new biomarkers for this aggressive sarcoma subgroup. Conclusions: Molecular evaluation of UUS provides novel insights into the biology, prognosis, phenotype, and possible treatment of these tumors.
  • Koebel, Martin, et al. (författare)
  • Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry
  • 2014
  • Ingår i: Histopathology. - : Wiley-Blackwell. - 0309-0167 .- 1365-2559. ; 64:7, s. 1004-1013
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsTo assess the variation in ovarian carcinoma type diagnosis among gynaecological pathologists from Nordic countries, and whether a rationally designed panel of immunohistochemical markers could improve diagnostic reproducibility. Methods and resultsEight pathologists from four countries (Sweden, Denmark, Norway, and Finland) received an educational lecture on the diagnosis of ovarian carcinoma type. All tumour-containing slides from 54 ovarian carcinoma cases were independently reviewed by the participants, who: (i) determined type purely on the basis of histology; (ii) indicated whether they would apply immunohistochemistry in their routine practice; and (iii) determined type after reviewing the staining results. The results for six markers (WT1, p53, p16, HNF-1, ARID1A, and progesterone receptor) were determined for all 54 cases, by staining of a tissue microarray. The median concordance with central review diagnosis was 86%, and significantly improved to 90% with the incorporation of immunostaining results (P=0.0002). The median interobserver agreement was 78%, and significantly improved to 85% with the incorporation of immunostaining results (P=0.0002). ConclusionsUse of the immunostaining results significantly improved both diagnostic accuracy and interobserver agreement. These results indicate that ovarian carcinoma type can be reliably diagnosed by pathologists from different countries, and also demonstrate that immunohistochemistry has an important role in improving diagnostic accuracy and agreement between pathologists.
  • Nastic, Denis, et al. (författare)
  • A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis
  • Ingår i: International Journal of Gynecological Pathology. - : Lippincott Williams and Wilkins. - 0277-1691 .- 1538-7151. ; 36:4, s. 339-347
  • Tidskriftsartikel (refereegranskat)abstract
    • Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53, and DNA ploidy. A representative H&E slide was scanned digitally and made available to 12 gynecologic pathologists in 4 Nordic countries: Finland, Denmark, Sweden, and Norway. Reviewers diagnosed the cases both before and after being provided with the biomarker results. The interobserver percent agreement and Cohen κ improved from 75.8% (κ=0.52, moderate) to 84% (κ=0.68, substantial) with inclusion of the biomarker panel. Agreement with the subsequent hysterectomy diagnosis also improved from 83.6% (κ=0.67) to 88.7% (κ=0.77). There was no statistical improvement between a reflex (84% agreement) and a reflective testing algorithm (82.9% agreement), suggesting that the selective use of biomarkers is appropriate. Difficult cases were almost exclusively high-grade tumors. Finally, a statistical model indicated that only P53 and DNA ploidy, in conjunction with an H&E review, had an impact on the decision to upgrade or downgrade cases.
  • Epstein, E., et al. (författare)
  • Gray-scale and color Doppler ultrasound characteristics of endometrial cancer in relation to stage, grade and tumor size
  • 2011
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - : John Wiley and Sons Inc.. - 1469-0705. ; 38:5, s. 586-593
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To describe the gray-scale and vascular characteristics of endometrial cancer in relation to stage, grade and size using two-dimensional (2D)/three-dimensional (3D) transvaginal ultrasound. Methods This was a prospective multicenter study including 144 women with endometrial cancer undergoing transvaginal ultrasound before surgery. The sonographic characteristics assessed were echogenicity, endometrial/myometrial border, fibroids, vascular pattern, color score and tumor/uterus anteroposterior (AP) ratio. Histological assessment of tumor stage, grade, type and growth pattern was performed. Results Hyperechoic or isoechoic tumors were more often seen in Stage IA cancer, whereas mixed or hypoechoic tumors were more often found in cancers of Stage IB or greater (P = 0.003). Hyperechogenicity was more common in Grade 1-2 tumors (i.e. well or moderately differentiated) (P = 0.02) and in tumors with a tumor/uterine AP ratio of <50% (P = 0.002), whereas a non-hyperechoic appearance was more commonly found in Grade 3 tumors (i.e. poorly differentiated) and in tumors with a tumor/uterine AP ratio of >= 50%. Multiple global vessels were more often seen in tumors of Stage IB or greater than in Stage IA tumors (P = 0.02), in Grade 3 tumors than in Grade 1 and 2 tumors (P = 0.02) and in tumors with a tumor/uterine AP ratio of >= 50% (P < 0.001). A moderate/high color score was significantly more common in tumors of higher stage (P = 0.03) and larger size (P = 0.001). Conclusion The sonographic appearance of endometrial cancer is significantly associated with tumor stage, grade and size. More advanced tumors often have a mixed/hypoechoic echogenicity, a higher color score and multiple globally entering vessels, whereas less advanced tumors are more often hyperechoic and have no or a low color score. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.
  • Epstein, Elisabeth, et al. (författare)
  • Sonographic characteristics of squamous cell cancer and adenocarcinoma of the uterine cervix.
  • 2010
  • Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : John Wiley and Sons Inc.. - 1469-0705. ; Apr 8, s. 512-516
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To describe the sonographic characteristic of squamous cell cancer (SCC) and adenocarcinoma (AC) of the cervix using transvaginal ultrasound. METHODS: Women with early stage cervical cancer undergoing transvaginal ultrasound examination prior to surgery were prospectively included. The sonographic characteristics were assessed with regard to tumor morphology, vascularization, size, extension and location. Histological assessment of tumor subtype, size, growth pattern, extension, location was performed. Both sonographic and histological assessments were done according to a standardized protocol. RESULTS: Fifty-five women were recruited. Ten were excluded since no tumor was seen on ultrasound and 5 because radical surgery was aborted due to positive lymph nodes, detected by the sentinel node technique. Among the remaining 40 women 20 had AC and 20 SCC. At pathological examination 34 women had tumors confined to the cervix, 3 had parametrial and 3 vaginal invasion. Hypoechoic echogenicity was associated with SCC in 73% (11/15), while isoechoic echogenicity indicated AC in 68% (13/19) of the women (p=0.03). Mixed echogenicity (n=4) showed a non-significant relation to larger tumor volume (p=0.23). Hyperechoic echogenicity was found in 2 women, both with the less malignant villoglandular AC. Color Doppler signals were found in all AC and 90% (18/20) of the SCC, as compared to most normal cervical tissue with virtually no detectable vascularization. CONCLUSIONS: We found that the sonographic appearance of SCC and AC differs, a knowledge that can be of use in the clinical evaluation of cervical tumors. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
  • Hardell, Elin, et al. (författare)
  • Validation of a Mitotic Index Cutoff as a Prognostic Marker in Undifferentiated Uterine Sarcomas
  • Ingår i: American Journal of Surgical Pathology. - : Lippincott Williams & Wilkins. - 0147-5185 .- 1532-0979. ; 41:9, s. 1231-1237
  • 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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