Hans Olsson

ImmunoCyt a useful method in the follow-up protocol for patients with urinary bladder carcinoma

Objective: To evaluate the ImmunoCytTM test - a urine-bound test for the detection of malignant transitional cells. Patients and Methods: ImmunoCytTM was compared with the standard investigation at our hospital for bladder cancer - cystoscopy, cytological examination of bladder wash material and, if necessary, a histological examination. A voided urine sample was collected before cystoscopy. We investigated 121 patients; seven specimens could not be evaluated. Results: Thirty-one of the 114 patients had a histologically proven urinary bladder carcinoma. All 31 cases were positive in the ImmunoCytTM test. Twenty-six of the 83 negative cases were ImmunoCytTM positive. The sensitivity was 100% and the specificity was 68.7%. Conclusion: ImmunoCytTM is easily applicable in a small laboratory and has high sensitivity and acceptable specificity.

Reproducibility of human epidermal growth factor receptor 2 analysis in primary breast cancer - A national survey performed at pathology departments in Sweden.

Background. HER2 is a treatment predictive factor for the effect of trastuzumab and associated with poor prognosis in breast cancer. The analysis of HER2 must be performed with good quality, with regard to both the immunohistochemical (IHC) and in situ hybridization (ISH) analysis. Material and methods. A tissue microarray (TMA) including 11 breast cancer samples was sent twice (once in 2005 and again in 2006) to 24 pathology departments in Sweden. A questionnaire was also sent to the departments in 2006. Results. With IHC, all departments reported the same results (0/1+ vs. 2+ vs. 3 + ) for three (2005) and six samples (2006). The mean kappa-value increased from 0.67 to 0.77, indicating a good reproducibility at both occasions. With fluorescence-ISH (FISH), the 11 departments using this technique reported the same results (amplified vs. normal) for nine (2005) and ten samples (2006). The mean kappa-value showed very good reproducibility both 2005 and 2006 (0.92 and 0.96, respectively). Based on the answers from the participating departments, the questionnaire revealed that 31% of primary breast cancer diagnosed in 2006 (n = 5 043) were 2 + /3+. FISH analysis of 2+ confirmed 12% of the samples to be amplified. The corresponding figure for 3 + was 90%. In total, 14.3% of the samples were HER2 positive (2+ and amplified, or 3 + ). Discussion. The results obtained in this study indicate that the reproducibility for HER2 analysis is good (IHC) and very good (FISH) between the pathology departments in Sweden using TMA-based tumor samples. In 2006, 14.3% of invasive breast cancers were HER2 positive.

Population-based study on prognostic factors for recurrence and progression in primary stage T1 bladder tumours

Abstract Objective. Stage T1 urothelial carcinoma of the bladder (UCB) exhibits heterogeneous clinical behaviour, and the treatment is controversial. The aim of this study was to evaluate prognostic factors for UCB in a defined, population-based cohort comprising patients with a first time diagnosis of primary stage T1 UCB. Material and methods. The study population initially consisted of 285 patients with primary stage T1 UCB reported to the regional Bladder Cancer Registry in the Southeast Healthcare Region of Sweden from 1992 to 2001. The histological specimens were re-evaluated concerning stage, substaging of T1, World Health Organization (WHO) grade, lymphovascular invasion (LVI), tumour volume and total resected volume. Hospital records provided data on tumour size and multiplicity, occurrence of possible relapse and/or progression, death from UCB and whether treatment was given. Results. After re-evaluation, the study population comprised 211 patients. The median follow-up time was 60 months. LVI was a prognostic factor for UCB progression and recurrence. Tumour size larger than 30 mm and multiplicity increased the risk of recurrence. T1 substaging, tumour volume and total resected volume were not associated with recurrence or tumour progression. Conclusions. LVI is significantly correlated with progression and recurrence in patients with primary stage T1 UCB. Therefore, the presence of LVI should be evaluated in every new case of T1 UCB.

HER2 status in primary stage T1 urothelial cell carcinoma of the urinary bladder

Abstract Objective. The HER2 receptor is involved in pathways essential for cell proliferation, and is an important predictive and prognostic factor in breast cancer. HER2 probably plays a critical role in many types of cancer, including urothelial carcinoma of the bladder (UCB). Stage T1 UCB exhibits heterogeneous clinical behaviour, and the frequency of HER2 expression in such disease has not been thoroughly examined. The aim of this study was to use an immunohistochemical technique to evaluate the frequency of HER2 expression in a defined population-based cohort of patients registered as having primary stage T1 UCB. Material and methods. The initial study population comprised 285 patients registered as having primary stage T1 UCB. The original histological specimens were re-evaluated with regard to T stage and World Health Organization grade. Hospital records provided information on tumour size, multiplicity, possible presence of histologically proven recurrence and progression. The patients were followed for at least 5 years or until death. In tumours still considered stage T1 after re-evaluation, HER2 was investigated by immunohistochemistry of paraffin-embedded material and scored according to the guidelines used in breast cancer. Results. After histopathological re-evaluation, 201 patients were still T1 UCB and could be investigated regarding HER2 expression. HER2 overexpression was observed in 25 of those patients (12.4%). HER2 status was not significantly associated with recurrence or progression. Conclusions. HER2 was overexpressed in 12.4% of the present cohort of patients with primary stage T1 UCB. There was no significant association between tumour HER2 status and prognosis.

The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS).

Study Type – Diagnostic (case series)

Immunohistochemical Evaluation of Cell Cycle Regulators Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer

Background and Objective. The cell cycle is regulated by proteins at different checkpoints, and dysregulation of this cycle plays a role in carcinogenesis. Matrix metalloproteinases (MMPs) are enzymes that degrade collagen and promote tumour infiltration. The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder (UCB). Patients and Methods. This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder. Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs. Results. Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence. Also, normal p16 expression was related to a lower risk of tumour progression. MMP2, p21, cyclin D1, and pRb showed no significant results that could estimate progression or recurrence. Conclusions. Normal p16 expression is associated with a lower risk of tumour progression, but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB.

Object-oriented solvers for initial value problems

The Godess (Generic Ordinary Differential Equations Solving System) Project aims at development of an object-oriented solver for initial value problems. In this project, the use of object-oriented techniques has been instrumental in development, testing, evaluation and verification of methods and control strategies. Based on comparisons with traditional solvers, we find that Godess is competitive with respect to accuracy and computational speed. These experiments demonstrate that this very generic solver is of real practical value.

Efficient Merging, Construction, and Maintenance of Evolutionary Trees

We present new techniques of efficiently merging and updating partial evolutionary trees in the so called experiment model. We show that two partial evolutionary trees for disjoint sets of species can be merged using experiments in time O(dn), where n is the size of the resulting evolutionary tree and d is its maximum degree. We prove our upper time bound for merging evolutionary trees to be asymptotically optimal. We show also that after O(n log n)-time preprocessing, a partial evolutionary tree can be maintained under a sequence of m species insertions or deletions in time O(dm log(n + m)). By applying our algorithm for merging evolutionary trees, or alternatively, our algorithm for updating evolutionary trees, we obtain an O(dn log n)-time bound on the problem of constructing an evolutionary tree of size n and maximum degree d from experiments. The classic O(n log n)-time bound on sorting in the comparison model can be seen as a very special case of this upper bound.

Efficient Merging and Construction of Evolutionary Trees

In this paper we study the algorithmic problem of constructing rooted evolutionary trees in the so-called experiment model. This model was first presented by Kannan, Lawler, and Warnow (J. Algorithms21 (1996), 26?50). We present a new technique of efficiently merging partial evolutionary trees in this model. We show that two partial evolutionary trees for disjoint sets of species can be merged using experiments in time O(dn), where n is the total number of species in the resulting evolutionary tree and d is its maximum degree. We prove our upper time bound on merging evolutionary trees to be asymptotically optimal. By applying our algorithm for merging evolutionary trees we obtain an O(dnlogn)-time bound on the problem of constructing an evolutionary tree for n species and maximum degree d from experiments. The classic O(nlogn)-time bound on sorting in the comparison-based model can be seen as a very special case of this upper bound.

Optimal Broadcasting in Almost Trees and Partial k-trees

We consider message broadcasting in networks that have almost tree topology. The source node of the input network has a single message which has to be broadcasted to all nodes of the network. In every time unit each node that has already received the message can send it to one of its neighbors. A broadcasting scheme prescribes in which time unit a given node should send a message to which neighbor. It is minimum if it achieves the smallest possible time for broadcasting the message from the source to all nodes. We give the following algorithms to construct a minimum broadcasting scheme for different types of weakly cyclic networks: A linear-time algorithm for networks whose cycles are node-disjoint and in which any simple path intersects at most O(1) cycles. An O(nlogn)-time algorithm for networks whose cycles are edge-disjoint and in which a node can belong to at most O(1) cycles. An O(nk log n) -time algorithm for networks whose each edge-biconnected component is convertible to a tree by removal of at most k edges. We also present an O(n4k+s)-time algorithm for constructing a minimum broadcasting scheme for partial k-trees.