Biomedical subjects

Håvard E Danielsen

Publications and source records attributed to Håvard E Danielsen.

8 recordsLinked to original sources

PubMed2006

Image cytometry DNA ploidy correlates with histological subtypes in endometrial carcinomas.

Image cytometric DNA ploidy analysis of endometrial carcinomas was performed to determine whether ploidy status and ploidy-related parameters like DNA index, percentage of cells exceeding 5c and 9c, correlate with histologic subtype. This is a prospective study of 391 patients with stage I endometrial carcinoma which included 331 (85%) endometrioid adenocarcinoma, 22 (6%) serous adenocarcinoma, 7 (2%) clear cell adenocarcinoma, 2 (0.5%) small cell carcinoma, 1 (0.3%) undifferentiated carcinoma, and 28 (7%) unclassifiable adenocarcinoma. Twenty-five percent of endometrioid adenocarcinomas were non-diploid. In contrast, all clear cell adenocarcinomas and 21/22 (95%) of serous adenocarcinomas were non-diploid. Hyperdiploidy (25 cases) was found only in endometrioid adenocarcinomas. Mean DNA index of the stemline in serous adenocarcinoma (1.72) and clear cell adenocarcinoma (1.81) was higher than in endometrioid adenocarcinoma (1.1). The difference in ploidy-related parameters between endometrioid adenocarcinoma and serous adenocarcinoma was highly significant (P<0.001). In addition, Grade 3 endometrioid adenocarcinoma showed significant difference in all ploidy-related parameters compared with grade 1 and grade 2 tumors (P<0.001). Our results show that DNA ploidy-related parameters may be valuable in subtyping histologically difficult cases of endometrial carcinomas.

Adenocarcinoma↗

PubMed2006

Prognostic value of adaptive textural features--the effect of standardizing nuclear first-order gray level statistics and mixing information from nuclei having different area.

BACKGROUND: Nuclear texture analysis is a useful method to obtain quantitative information for use in prognosis of cancer. The first-order gray level statistics of a digitized light microscopic nuclear image may be influenced by variations in the image input conditions. Therefore, we have previously standardized the nuclear gray level mean value and standard deviation. However, there is a clear relation between nuclear DNA content, area, first-order statistics, and texture. For nuclei with approximately the same DNA content, the mean gray level increases with an increasing nuclear area. The aims of the present methodical work were to study: (1) whether the prognostic value of adaptive textural features varies with nuclear area, and (2) the effect of standardizing nuclear first-order statistics. METHODS: Nuclei from 134 cases of ovarian cancer were grouped into intervals according to nuclear area. Adaptive features were extracted from two different image sets, i.e., standardized and non-standardized nuclear images. RESULTS: The prognostic value of adaptive textural features varied strongly with nuclear area. A standardization of the first-order statistics significantly reduced this prognostic information. Several single features discriminated the two classes of cancer with a correct classification rate of 70%. CONCLUSION: Nuclei having an area between 2000-4999 pixels contained most of the class distance information between the good and poor prognosis classes of cancer. By considering the relation between nuclear area and texture, we avoided a loss of information caused by standardizing the first-order statistics and mixing data from cells having different nuclear area.

Algorithms↗

PubMed2005

beta-catenin expression, DNA ploidy and clinicopathological features in ovarian cancer: a study in 253 patients.

The CTNNB1 gene and its product beta-catenin, a regulator of the Wnt signalling pathway, is often mutated and deregulated in human malignancies. Down stream targets of the Wnt signalling pathway are linked to genomic instability. In this study, the impact of beta-catenin expression on genomic instability in ovarian carcinoma, as determined by DNA ploidy, was investigated. Expression of beta-catenin was examined by immunohistochemistry in 253 ovarian carcinomas. The results were related to genomic instability and clinicopathological features of the patients. Membrane associated staining of beta-catenin was detected in nearly all cases with no correlation to clinical parameters. Most of the samples also had cytoplasmic (84%), while only 13% had nuclear beta-catenin localisation. A significant association between beta-catenin expression (cytoplasmic and nuclear) and histological subtype and degree of differentiation was observed. Nuclear beta-catenin was almost exclusively present in endometroid carcinomas. 53% of all endometroid tumours were positive for nuclear beta-catenin expression (P<0.0001). Mucinous carcinomas had the highest degree of cytoplasmic beta-catenin expression (92%), followed by endometroid (92%), mixed (90%), serous (82%), unclassified adenocarcinomas (81%), carcinomas clear cell and (70%), (P=0.01). Tumours with differentiation grade 1 (16%) and 2 (24%) had higher nuclear beta-catenin expression than grade 3 and clear cell carcinomas (6%) (P=0.012). Better prognostic outcome was found for patients with nuclear beta-catenin localisation as compared to the cases without (P=0.027). In conclusion, the study showed no correlation between beta-catenin expression in ovarian carcinoma and FIGO stage and genomic instability as determined by DNA ploidy status. However, nuclear beta-catenin expression was strongly associated with endometroid histological subtype. Finally, in ovarian cancer, although beta-catenin staining seems to be of prognostic importance with respect to nuclear staining in univariate analysis, only DNA ploidy status, histological grade and FIGO staging were of independent prognostic significance in multivariate analysis.

Cytoskeletal Proteins↗

PubMed2005

Adenomas and follicular carcinomas of the thyroid display two major patterns of chromosomal changes.

It was recently shown by flow and static cytometry that a large sub-group of follicular adenomas of the thyroid--fetal/embryonal adenomas--display an aneuploid phenotype. It was also shown that thyroid lesions with a DNA content within the triploid range were either fetal adenomas or follicular carcinomas with a fetal adenoma growth pattern. Follicular tumours with growth patterns other than the so-called fetal adenoma-like pattern were usually diploid or near-diploid. In an attempt to clarify the pattern of chromosomal imbalances in follicular tumours, comparative genomic hybridization (CGH) analysis was performed in a series of 18 follicular neoplasms (ten fetal/embryonal and four common follicular adenomas and four minimally invasive follicular carcinomas). For each tumour, the DNA content was determined by flow cytometry and, in some cases, also by static cytometry. Finally, the copy number of selected chromosomes was determined by interphase fluorescence in situ hybridization (FISH) using centromere probes. With the exception of the single diploid fetal adenoma, all fetal adenomas displayed several DNA copy number changes, with frequent gains of several chromosomes, which were found to be either tetrasomic or trisomic by FISH. This genetic pattern was also present in the single case of follicular carcinoma with aneuploidy and fetal adenoma-like growth pattern. Follicular adenomas other than fetal adenomas, and the remaining follicular carcinomas, showed more losses than gains of chromosomes. These results suggest that follicular tumourigenesis may follow at least two pathways: one characterized by prominent aneuploidy and numerous gains, in which the tumours display a fetal adenoma-like growth pattern; and another accompanied by less obvious aneuploidy or even quasi-diploidy and dominant chromosome losses, in which the tumours display a common follicular architecture.

Adenoma↗

PubMed2004

Evaluation of genomic changes in a large series of malignant ovarian germ cell tumors--relation to clinicopathologic variables.

Malignant ovarian germ cell tumors (mOGCT) affect women in their reproductive years, making fertility-saving treatment important. A reliable prediction of the clinical behavior is essential for an optimal therapeutic approach. The genetic changes and molecular mechanisms underlying these rare tumors remain poorly understood. To address these issues, we performed DNA ploidy analysis by high-resolution image cytometry in a series of 47 mOGCT and correlated the findings with the DNA copy number changes detected by comparative genomic hybridization (CGH) and clinical outcome. Of 47 tumors, 15 were diploid, 14 were tetraploid, 2 were polyploid, and 13 were aneuploid. All the immature teratomas were diploid, in contrast to the dysgerminomas and endodermal sinus tumors. The International Federation of Gynecology and Obstetrics (FIGO) staging, residual tumors after surgery, and DNA ploidy distribution were significant, independent prognostic factors in survival analysis. The study revealed that the number of DNA copy number aberrations was increased in tetraploid and aneuploid tumors as compared to diploid tumors. Furthermore, a high percentage of aneuploid nuclei in a sample were associated with a complex CGH profile of the tumor in question. The present study confirms that DNA aneuploidy assessment by image analysis may be linked to genetic instability, which is detected as genetic aberrations by CGH. DNA ploidy gives significant prognostic information in addition to the clinical stage in mOGCT with FIGO stage II-IV.

Adolescent↗

PubMed2004

Low dimensional adaptive texture feature vectors from class distance and class difference matrices.

In many popular texture analysis methods, second or higher order statistics on the relation between pixel gray level values are stored in matrices. A high dimensional vector of predefined, nonadaptive features is then extracted from these matrices. Identifying a few consistently valuable features is important, as it improves classification reliability and enhances our understanding of the phenomena that we are modeling. Whatever sophisticated selection algorithm we use, there is a risk of selecting purely coincidental "good" feature sets, especially if we have a large number of features to choose from and the available data set is limited. In a unified approach to statistical texture feature extraction, we have used class distance and class difference matrices to obtain low dimensional adaptive feature vectors for texture classification. We have applied this approach to four relevant texture analysis methods. The new adaptive features outperformed the classical features when applied to the most difficult set of 45 Brodatz texture pairs. Class distance and difference matrices also clearly illustrated the difference in texture between cell nucleus images from two different prognostic classes of early ovarian cancer. For each of the texture analysis methods, one adaptive feature contained most of the discriminatory power of the method.

Algorithms↗

PubMed2003

Genome profiles of bilateral dysgerminomas, a unilateral gonadoblastoma, and a metastasis from a 46, XY phenotypic female.

We present a case report of a 16-year-old, phenotypic female with bilateral dysgerminomas, a unilateral gonadoblastoma, and a peritoneal metastasis. The patient's constitutional karyotype was 46,XY. The chromosomal copy number, examined by the comparative genomic hybridization technique, showed 3 gains in the dysgerminoma of the right ovary, 6 gains in the dysgerminoma of the left ovary, and 2 gains and 1 loss in the gonadoblastoma of the left ovary. The metastasis showed 5 gains of which 4 were also observed in the dysgerminoma of the left ovary. The DNA ploidy classifications of the gonadoblastoma and the dysgerminoma in the right ovary were tetraploid, whereas the dysgerminoma in the left ovary and the metastasis were aneuploid. We therefore propose that the metastasis most probably developed from the dysgerminoma of the left ovary.

Adolescent↗

PubMed2002

Gross genomic aberrations in precancers: clinical implications of a long-term follow-up study in oral erythroplakias.

PURPOSE: Gross genomic aberrations are increasingly seen as a cause rather than a consequence of carcinogenesis. Carcinomas may be prevented by systemically acting agents when used in high-risk individuals. If gross genomic aberrations could be shown to be predictive markers in precancers, they could serve as a tool for identifying high-risk individuals to be included in chemopreventive trials. PATIENTS AND METHODS: To investigate the predictive power of gross genomic aberrations in several types of oral premalignancies, we analyzed 57 biopsies from oral erythroplakias of 37 patients, both histologically and for DNA content. DNA content was measured by high-resolution image cytometry, and distribution histograms of DNA content were generated and interpreted according to established protocols. The primary end point was cancer-free survival. RESULTS: Fifty-seven dysplastic oral red lesions from 37 patients were investigated. Forty-one lesions from 25 patients were classified with aberrant DNA content (DNA aneuploidy), of which 23 patients (92%) later developed an oral carcinoma (after a median observation time of 53 months; range, 29 to 79 months). Of 12 patients having altogether 16 lesions with normal DNA content, none developed a carcinoma (median observation time, 98 months; range, 23 to 163 months; P <.001). In multivariate analysis, DNA content was a significant prognostic factor (P <.001), whereas histologic grade, sex, use of tobacco, size and location of lesions, and the presence multiple of lesions were not. CONCLUSION: Gross genomic aberrations are highly predictive for the subsequent occurrence of carcinomas from a wide range of oral premalignancies.

Aged↗