Publications by authors named "Tor Audun Klingen"

6 Publications

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Tumor-associated lymphocytes and macrophages are related to stromal elastosis and vascular invasion in breast cancer.

J Pathol Clin Res 2021 Sep 2;7(5):517-527. Epub 2021 Jun 2.

Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway.

The tumor microenvironment plays a critical role in breast cancer progression. Here, we investigated tumor-infiltrating lymphocytes (TILs) and associations with macrophage numbers, tumor stromal elastosis, vascular invasion, and tumor detection mode. We performed a population-based retrospective study using data from The Norwegian Breast Cancer Screening Program in Vestfold County (2004-2009), including 200 screen-detected and 82 interval cancers. The number of TILs (CD45+, CD3+, CD4+, CD8+, and FOXP3+) and tumor-associated macrophages (CD163+) was counted using immunohistochemistry on tissue microarray slides. Lymphatic and blood vessel invasion (LVI and BVI) were recorded using D2-40 and CD31 staining, and the amount of elastosis (high/low) was determined on regular HE-stained slides. High numbers of all TIL subsets were associated with LVI (p ≤ 0.04 for all), and high counts of several TIL subgroups (CD8+, CD45+, and FOXP3+) were associated with BVI (p ≤ 0.04 for all). Increased levels of all TIL subsets, except CD4+, were associated with estrogen receptor-negative tumors (p < 0.001) and high tumor cell proliferation by Ki67 (p < 0.001). Furthermore, high levels of all TIL subsets were associated with high macrophage counts (p < 0.001) and low-grade stromal elastosis (p ≤ 0.02). High counts of CD3+, CD8+, and FOXP3+ TILs were associated with interval detected tumors (p ≤ 0.04 for all). Finally, in the luminal A subgroup, high levels of CD3+ and FOXP3+ TILs were associated with shorter recurrence-free survival, and high counts of FOXP3+ were linked to reduced breast cancer-specific survival. In conclusion, higher levels of different TIL subsets were associated with stromal features such as high macrophage counts (CD163+), presence of vascular invasion, absence of stromal elastosis, as well as increased tumor cell proliferation and interval detection mode. Our findings support a link between immune cells and vascular invasion in more aggressive breast cancer. Notably, presence of TIL subsets showed prognostic value within the luminal A category.
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http://dx.doi.org/10.1002/cjp2.226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363927PMC
September 2021

Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer.

PLoS One 2017 15;12(2):e0171853. Epub 2017 Feb 15.

Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.

Presence of lymph node (LN) metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218), as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996-2009). Sections were reviewed for the largest metastatic tumor diameter (TD-MET), nodal afferent and efferent vascular invasion (AVI and EVI), extra-nodal extension (ENE), number of ENE foci, as well as circumferential (CD-ENE) and perpendicular (PD-ENE) diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT) diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS) or breast cancer specific survival (BCSS). Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value) in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively). To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171853PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310784PMC
August 2017

Evaluation of Tumor Cell Proliferation by Ki-67 Expression and Mitotic Count in Lymph Node Metastases from Breast Cancer.

PLoS One 2016 8;11(3):e0150979. Epub 2016 Mar 8.

Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway.

Few studies have addressed the risk of recurrence by assessing proliferation markers in lymph node metastasis from breast cancer. Here, we aimed to examine Ki-67 expression and mitotic count in lymph nodes in comparison with primary tumors. A cohort of node positive breast cancer (n = 168) was studied as a part of the prospective Norwegian Breast Cancer Screening Program (1996-2009). The percentage of Ki-67 positivity was counted per 500 tumor cells in hot-spot areas (x630). Mitotic count was conducted in the most cellular and mitotic active areas in 10 high power fields (x400). Our results showed that Ki-67 and mitotic count were significantly correlated between primary tumor and lymph nodes (Spearman`s correlation 0. 56 and 0.46, respectively) and were associated with most of the histologic features of the primary tumor. Univariate survival analysis (log-rank test) showed that high Ki-67 and mitotic count in the primary tumor and lymph node metastasis significantly predicted risk of recurrence. In multivariate analysis, mitotic count in the lymph node metastasis was an independent predictor of tumor recurrence. In conclusion, proliferation markers in lymph node metastases significantly predicted disease free survival in node positive breast cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150979PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783103PMC
August 2016

Sinonasal adenoid cystic carcinoma following formaldehyde exposure in the operating theatre.

J Occup Med Toxicol 2014 17;9(1):43. Epub 2014 Dec 17.

Department of Environmental and Occupational Medicine, Oslo University Hospital, PO Box 4956, Nydalen, Oslo, NO-0424 Norway.

We present a case report of an auxiliary nurse who developed an adenoid cystic carcinoma in her left maxillary sinus following occupational exposure to formaldehyde in the operating theatre. Currently, the epidemiological evidence that formaldehyde can cause cancer in humans is considered to be limited. Previous case-control-studies of formaldehyde and sinonasal cancer have mainly investigated subjects who were concomitantly exposed to wood dust, a known risk factor to the development of sinonasal adenocarcinoma of intestinal type. Our case report presents a patient who has developed an adenoid cystic carcinoma following exposure to formaldehyde. We suggest that the occupational physician remains alert to formaldehyde as an occupational hazard among health care workers.
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http://dx.doi.org/10.1186/s12995-014-0043-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279905PMC
December 2014

Secondary breast cancer: a 5-year population-based study with review of the literature.

APMIS 2009 Oct;117(10):762-7

Department of Pathology, Vestfold County Hospital, Halvdan Wilhelmsens Allè 17, Tønsberg, Norway.

Secondary tumours in the breast are rare. Based on literature, an incidence of 0.4-2% is reported. In this population-based study, secondary breast tumours from a 5-year period (2001-2005), not including metastasis from contralateral breast carcinoma, were reviewed (Vestfold County, Norway). A total of 722 patients with breast malignancies were found in this population (89.3% from Vestfold County Hospital). Ten of these, approximately 1.4%, were metastatic tumours, representing four cutaneous melanomas, three pulmonary carcinomas and three malignant lymphomas. The tumours were often solitary, palpable and close to the skin. Radiologically, the lesions mostly resembled primary carcinomas by mammography and ultrasound, which differs from other studies. Comparison with a known primary tumour and use of immunohistochemical profiling is of crucial importance. Melanoma markers (Melan-A, HMB-45, S-100 protein), lung cancer markers (Cytokeratins, TTF1, Chromogranin, Synapthophysin) and lymphoid markers (CD3, CD20) usually help to confirm a secondary breast tumour diagnosis. This approach is especially indicated in diffusely growing tumours with lack of glandular structure and high-grade cytological features, and staining for ER and GCDFP15 may be helpful. Thus, the diagnosis of a breast metastasis may be suspected by careful mammography and ultrasound imaging, although some cases have atypical radiological features, and histological examination might be necessary to ensure a correct diagnosis and appropriate treatment.
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http://dx.doi.org/10.1111/j.1600-0463.2009.02529.xDOI Listing
October 2009

Full-field digital mammography compared to screen film mammography in the prevalent round of a population-based screening programme: the Vestfold County Study.

Eur Radiol 2008 Jan 7;18(1):183-91. Epub 2007 Aug 7.

Department of Radiology, Vestfold Hospital, Halfdan Wilhelmsens Alle 17, 3116 Tønsberg, Norway.

The purpose of the study was to compare the performance of full-field digital mammography (FFDM) with soft-copy reading to screen film mammography (SFM) used during the first prevalent 2-year round of population-based screening. A total of 18,239 women aged 50-69 years were screened with FFDM as part of the Norwegian Breast Cancer Screening Programme (NBCSP). Process indicators were compared to data from 324,763 women screened with SFM using the common national database of the NBCSP. The cancer detection rates were 0.77% (140/18,239) for FFDM and 0.65% (2,105/324,763) for SFM (p = 0.058). For ductal carcinoma in situ (DCIS) alone, the results were: FFDM 0.21% (38/18,239) compared to SFM 0.11% (343/324,763) (p < 0.001). Recall rates due to positive mammography were for FFDM 4.09% (746/18,239), while for SFM 4.16% (13,520/324,764) (p = 0.645), due to technically insufficient imaging: FFDM 0.22% (40/18,239) versus SFM 0.61% (1,993/324,763) (p < 0.001). The positive predictive value (PPV) in the FFDM group was 16.6% (140/843), while 13.5% (2,105/15,537) for SFM (p = 0.014). No statistically significant differences were recorded concerning histological morphology, tumour size, or lymph node involvement. In conclusion FFDM had a significantly higher detection rate for DCIS than SFM. For invasive cancers no difference was seen. FFDM also had a significantly higher PPV and a significantly lower technical recall rate.
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http://dx.doi.org/10.1007/s00330-007-0730-yDOI Listing
January 2008
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