| 1. |
- Epstein, Elisabeth, et al.
(författare)
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Early-stage cervical cancer: Tumor delineation by magnetic resonance imaging and ultrasound - A European multicenter trial
- 2013
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 128:3, s. 449-453
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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.
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| 2. |
- Harbst, Katja, et al.
(författare)
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Molecular profiling reveals low- and high-grade forms of primary melanoma.
- 2012
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
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Tidskriftsartikel (refereegranskat)abstract
- For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
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| 3. |
- Koebel, Martin, et al.
(författare)
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Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry
- 2014
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 94, s. 290A-290A
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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.
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| 4. |
- Darlin, Lotten, et al.
(författare)
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The sentinel node concept in early cervical cancer performs well in tumors smaller than 2 cm.
- 2010
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 117:2, s. 266-269
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of the study was to evaluate the sentinel node (SLN) concept for lymphatic mapping in early stage cervical cancer. METHODS: 105 women with early stage (1a1-2a) cervical cancer were scheduled for the sentinel node procedure in conjunction with a complete pelvic lymphadenectomy. The day before surgery, 1-1.5 mL 120MBq Tc(99) albumin nanocolloid was injected submucosally at four points around the tumor followed by a lymphoscintigram (LSG) to achieve an overview of the radiotracer uptake. RESULTS: During surgery, the overall detection rate (gamma probe) of at least one SLN was 90% (94/105 women) whereas at least one SLN was identified in 94% (61/65 women) with a tumor 2 cm) node without radiotracer uptake. The negative predictive value for patients with cervical cancers
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| 5. |
- Epstein, E., et al.
(författare)
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Gray-scale and color Doppler ultrasound characteristics of endometrial cancer in relation to stage, grade and tumor size
- 2011
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 38:5, s. 586-593
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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.
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| 6. |
- Epstein, Elisabeth, et al.
(författare)
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Sonographic characteristics of squamous cell cancer and adenocarcinoma of the uterine cervix.
- 2010
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Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; Apr 8, s. 512-516
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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.
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| 7. |
- Harbst, Katja, et al.
(författare)
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Multiple metastases from cutaneous malignant melanoma patients may display heterogeneous genomic and epigenomic patterns.
- 2010
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Ingår i: Melanoma Research. - 0960-8931. ; 20:5, s. 381-391
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Tidskriftsartikel (refereegranskat)abstract
- Disseminated melanoma is an aggressive disease with fatal outcome. Better understanding of the underlying biology is needed to find effective treatment. We applied microarray-based comparative genomic hybridization, gene expression and CpG island methylation analysis of primary tumors and multiple metastases from five melanoma patients with the aim of analyzing the molecular patterns of melanoma progression. Epigenetic profiling showed that the multiple metastases after a single primary melanoma share similar methylation patterns for many genes, although differences in methylation between the lesions were evident for several genes, example, PTEN, TFAP2C, and RARB. In addition, DNA copy number and global gene expression profiles of tumors from individual patients were highly similar, confirming common origin of metastases. Some of the identified genomic aberrations, for example, gain of chromosome 6p and loss of chromosomes 6q and 10, persisted during progression, indicating early changes highly important for melanoma development. Homozygous deletions at 3p26.1 and 6q23.2-q23.3 appeared in two consecutive metastases originating from the same primary tumor, respectively, in a mutually exclusive manner that provides evidence for two genetically different subclones. However, in another case, the similarity of the copy number aberrations in subsequent metastatic lesions suggests sequential metastatic development through the clonal evolution. These data are further corroborated by a switch in CDH1 and CDH2 expression between metastases from the same patient. In conclusion, our results provide evidence for different models of metastatic progression in melanoma.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Måsbäck, Anna, et al.
(författare)
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Problems in assessing multiple cutaneous melanoma. A review on the accuracy of a population based cancer registry.
- 2010
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821. ; 34, s. 262-266
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Tidskriftsartikel (refereegranskat)abstract
- Databases with information on malignant tumors are of great value for epidemiologic studies. From the Regional South Swedish Tumour Registry, which is of documented high quality, 24 patients out of 8008 with reported melanoma diagnosis 1973-2003 were reported as having multiple (>/=3) primary, invasive cutaneous malignant melanomas (CMM). Of the 76 tumours identified in these patients, 7 (9%) were found not to be invasive melanomas. Additional cases could be put into question since the lesions could be interpreted as epidermotropic metastases, a diagnosis which can be difficult to establish reliably by microscopic examination. Among the 24 patients we could also identify 8 (10%) additional lesions representing invasive CMM, not included in the Tumour Registry database. Thorough information concerning an earlier melanoma diagnosis and its site of presentation is needed from the clinician and the pathologist for optimal assessment of the histology and the prognostication of the patient, as well as proper reporting to a tumour registry. Identifying multiple primary malignant melanomas is also of special importance for counselling patients belonging to families with hereditary disease. In this study it is shown that diagnosing and reporting multiple malignant melanomas can be problematic due to insufficient communication and to the rare and deceptive capability of cutaneous metastases to imitate primary tumours.
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