Gynecologic and breast pathology
Posted on May 16th, 2011 by Björn Risberg
Head: Torill Sauer, Prof MD PhD
Vera Abeler MD PhD
Per Bøhler MD
Ben Davidson Ass.Prof MD PhD
Øystein Garred MD PhD
Bjørn Risberg MD PhD
Davidson´s group present Tenascin-X as a novel diagnostic marker of malignant mesothelioma
Posted on January 6th, 2010 by Björn Risberg
Yuan Y, Nymoen DA, Stavnes HT, Rosnes AK, Bjørang O, Wu C, Nesland JM, Davidson B.
Tenascin-X is a novel diagnostic marker of malignant mesothelioma.
Am J Surg Pathol. 2009 Nov;33(11):1673-82.
Tenascin-X protein expression was studied in 183 effusions (137 carcinomas of different origin, 37 mesotheliomas, and 9 reactive effusions) and 178 solid lesions (122 ovarian/peritoneal carcinomas and 56 mesotheliomas) using immunohistochemistry. Quantitative polymerase chain reaction analysis showed significantly higher TNXB mRNA level in mesotheliomas compared with ovarian and breast carcinomas (P < 0.001). By immunohistochemistry, tenascin-X protein expression was significantly higher in malignant mesothelioma compared with metastatic carcinoma in effusions (34 of 37 vs. 31 of 137 positive cases; sensitivity = 92% and specificity = 77%; P < 0.001). Reactive mesothelial cells had focal or no tenascin-X expression. Tenascin-X protein was detected in 41 of 56 mesothelioma biopsy specimens and was uniformly absent from all 122 ovarian carcinomas (sensitivity = 73% and specificity = 100%; P < 0.001). Our data suggest that tenascin-X may be a new diagnostic marker of malignant mesothelioma in the differential diagnosis of cancers involving the serosal cavities, particularly in the differential diagnosis between this tumor and ovarian/peritoneal serous carcinoma.
Madshus and Stang discuss: Internalization and intracellular sorting of the EGF receptor
Posted on January 6th, 2010 by Björn Risberg
Madshus IH, Stang E.
Internalization and intracellular sorting of the EGF receptor: a model for understanding the mechanisms of receptor trafficking.
J Cell Sci. 2009 Oct 1;122(Pt 19):3433-9.
In this Opinion article, we discuss the impact of signaling motifs, kinase activity and ubiquitylation on clathrin-dependent endocytosis and lysosomal sorting of EGFR. In addition, we discuss potential explanations for contradicting reports, and propose models for the recruitment of ligand-activated EGFR to clathrin-coated pits as well as for lysosomal sorting of ligand-activated EGFR.
News from Haraldsen´s group
Posted on April 14th, 2009 by Björn Risberg
Interleukin-33 - cytokine of dual function or novel alarmin?
Trends Immunol (in press) (online 7 Apr 2009)
PubMed 19359217
Haraldsen´s group presents interesting findings concerning IL-33 - may be involved in the control of endothelial cell activation
Posted on November 14th, 2008 by Björn Risberg
Küchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G. Publish in Am J Pathol. 2008 Oct;173(4):1229-42.
“Nuclear interleukin-33 is generally expressed in resting endothelium
but rapidly lost upon angiogenic or proinflammatory activation.”
Interleukin (IL)-33 is a novel member of the IL-1 family of
cytokines that promotes Th2 responses in lymphocytes as well
as the activation of both mast cells and eosinophils via the
ST2 receptor. Additionally, IL-33 has been proposed to act as
a chromatin-associated transcriptional regulator in both
endothelial cells of high endothelial venules and chronically
inflamed vessels. Here we show that nuclear IL-33 is expressed
in blood vessels of healthy tissues but down-regulated at the
earliest onset of angiogenesis during wound healing; in addition,
it is almost undetectable in human tumor vessels. Accordingly,
IL-33 is induced when cultured endothelial cells reach confluence
and stop proliferating but is lost when these cells begin to migrate.
However, IL-33 expression was not induced by inhibiting cell cycle
progression in subconfluent cultures and was not prevented by
antibody-mediated inhibition of VE-cadherin. Conversely, IL-33
knockdown did not induce detectable changes in either expression
levels or the cellular distribution of either VE-cadherin or CD31.
However, activation of endothelial cell cultures with either tumor
necrosis factor-alpha or vascular endothelial growth factor and
subcutaneous injection of these cytokines led to a down-regulation
of vascular IL-33, a response consistent with both its rapid
down-regulation in wound healing and loss in tumor endothelium.
In conclusion, we speculate that the proposed transcriptional
repressor function of IL-33 may be involved in the control of
endothelial cell activation.
Clausen´s group publish: On the mechanisms for aneuploidy in colorectal carcinoma
Posted on August 28th, 2008 by Björn Risberg
CONCLUSIONS:
A significant reduction of BUB1B level was
detected in aneuploid compared to diploid colorectal cancers,
consistent with earlier studies showing that loss of spindle
checkpoint function may be involved in development of DNA aneuploidy.
Our data also show that spindle proteins are overexpressed in
colorectal cancers, and that expression of the Aurora kinases is
associated with prognosis in colorectal cancer.
Cell Prolif. 2008 Aug;41(4):645-59. Links
Reduced level of the spindle checkpoint protein BUB1B is associated
with aneuploidy in colorectal cancers.Burum-Auensen E, DeAngelis PM,
Schjølberg AR, Røislien J, Mjåland O, Clausen OP. LINK
The Micrometastasis project group publish results in Breast and Prostate cancer patients
Posted on August 28th, 2008 by Björn Risberg
Prostate:
Post-treatment BM-aspirates were positive
for disseminated tumor cells (DTCs) in 17% of cases without correlation to any of the tested
variables. Out of 14 patients who had DTCs in BM prior to treatment,
all but one had become post-treatment negative. Out of 95 patients
with pre-treatment negative BM status, 18 (19%) had become post-treatment
positive. CONCLUSIONS: DTCs in BM were found in 17% of clinically
progression-free PC patients following RT. The detection of these
cells may provide PSA-independent prognostic information remaining
to be explored by prolonged follow-up.
Prostate. 2008 Jul 24. [Epub ahead of print] Link
Disseminated tumor cells in bone marrow following definitive radiotherapy
for intermediate or high-risk prostate cancer.Berg A, Bruland OS, Fosså SD,
Nesland JM, Berner A, Schirmer C, Lilleby W.LINK
Breast:
High vascular grades
determined by Chalkley counts were significantly associated with shorter
distant disease-free survival and breast cancer-specific survival in all
patients (P < 0.001, log-rank) and in node-negative patients not
receiving adjuvant systemic therapy (P < 0.05). In multivariate analysis,
both CD34 and CD105 Chalkley counts showed prognostic significance for
distant disease-free survival (P = 0.014 and P = 0.026), whereas CD34
also showed prognostic significance for breast cancer-specific survival
(P = 0.007). Vascular invasion and DTCs in the bone marrow showed
independent prognostic significance. DTC did not discriminate survival
for CD34 low Chalkley counts, whereas a very poor prognosis was observed
for DTC-positive patients with high CD34 counts. In node-negative patients
not receiving systemic chemotherapy, high CD34 and high CD105 counts in
combination identified patients with unfavorable outcome, as opposed to
all other CD34/CD105 combinations. CONCLUSIONS: Improved identification
of risk groups could be obtained by adding CD34 and CD105 vascular analysis
to DTC, vascular invasion, and other primary tumor factors. This may
facilitate the selection of candidates for adjuvant systemic therapy.
Clin Cancer Res. 2008 Apr 15;14(8):2341-50. Links
Vascularization in primary breast carcinomas: its prognostic significance
and relationship with tumor cell dissemination.Dhakal HP, Naume B,
Synnestvedt M, Borgen E, Kaaresen R, Schlichting E, Wiedswang G,
Bassarova A, Giercksky KE, Nesland JM. LINK
Jahnsen group publish: Depletion of CD4(+)CD25(+)CD127(lo) regulatory T cells does not increase allergen-driven T cell activation
Posted on August 28th, 2008 by Björn Risberg
Conclusion:
Our study showed that T cells from grass pollen-allergic
patients and non-atopic controls responded very differently to
grass pollen extract, but this difference could not be explained by
differences in regulatory T cell function. Further studies are needed
to understand the importance of regulatory T cells in allergy.
Published in Clin Exp Allergy. 2008 Jul 31.
Depletion of CD4(+)CD25(+)CD127(lo) regulatory T cells does not
increase allergen-driven T cell activation.Skrindo I, Farkas L,
Kvale EO, Johansen FE, Jahnsen FL. Link
New Papers from Davidson´s group on Claudin, Rsf-1, Dj-1 and Death receptors in ovarian and breast cancer
Posted on August 28th, 2008 by Björn Risberg
Kleinberg L, Holth A, Trope CG, Reich R, Davidson B.
Claudin upregulation in ovarian carcinoma effusions is associated
with poor survival.
Hum Pathol. 2008 May;39(5):747-57.
Davidson B, Wang TL, Shih IeM, Berner A
Expression of the chromatin remodeling factor Rsf-1 is down-regulated in breast carcinoma effusions.
Hum Pathol. 2008 Apr;39(4):616-22. Epub 2008 Mar 4
Davidson B, Hadar R, Schlossberg A, Sternlicht T,
Slipicevic A, Skrede M, Risberg B, Flørenes VA, Kopolovic J, Reich R.
Expression and clinical role of DJ-1, a negative regulator of PTEN,
in ovarian carcinoma.
Hum Pathol. 2008 Jan;39(1):87-95. Epub 2007 Oct 18. Links
Dong HP, Kleinberg L, Silins I, Flørenes VA, Tropé CG, Risberg B,
Nesland JM, Davidson B.Davidson B
Death receptor expression is associated with poor response to
chemotherapy and shorter survival in metastatic ovarian carcinoma.
Cancer. 2008 Jan 1;112(1):84-93.
The Liipat and Jahnsen group publish: Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour growth in a mouse model of B cell lymphoma
Posted on August 28th, 2008 by Björn Risberg
Our study showed that removal of CD25+ T(regs) enhanced anti-tumour
immunity against local growth of a B cell lymphoma and that
induction or expansion of T(regs) could be one mechanism by
which the growing tumour evades immune surveillance.
Published in Clin Exp Immunol. 2008 May;152(2):381-7. Epub 2008 Mar 12. Link
Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour
growth in a mouse model of B cell lymphoma.Heier I, Hofgaard PO,
Brandtzaeg P, Jahnsen FL, Karlsson M.
