| 11. |
- Glimelius, Ingrid, et al.
(författare)
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The effect of Eosinophil cationic protein (ECP) on Hodgkin lymphoma cell lines
- 2011
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Ingår i: Experimental Hematology. - : Elsevier BV. - 0301-472X .- 1873-2399. ; 39:8, s. 850-858
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Tidskriftsartikel (refereegranskat)abstract
- Background In classical Hodgkin lymphoma (HL), many eosinophils in tumour tissue indicate poor prognosis, probably caused by stimulation of the tumour cells, the Hodgkin Reed Sternberg (HRS) cells. However, eosinophils are primarily known for their role in innate immunity, where one function is to secrete the toxic substances eosinophil cationic protein (ECP), and eosinophil protein X (EPX). The aim of this study was to investigate the effects of ECP on HRS cells in vitro.Method The fluorometric microculture cytotoxicity-assay (FMCA) measured survival index (SI) of cells from the HL cell lines HDLM-2, KMH2, and L428 after incubation with ECP or EPX. The gene products of a coding ECP polymorphism, ECP97arg and ECP97thr, and ECPs, with different levels of glycosylation were investigated. Flow cytometry was used to monitor the effects of ECP on markers of cell death.Results A concentration dependent reduction of SI was seen after ECP treatment. For the B-cell derived cell lines, KMH2 and L428, ECP was cytotoxic with a dose response relationship similar to a previously investigated small-cell lung cancer cell-line. In contrast, for HDLM-2, which is a cell line of T-cell origin, the cytotoxicity was even more pronounced at the lowest concentrations tested, and then reached a plateau at about 0.018µM. At a concentration of 0.14µM of ECP, an SI of 71%±1.9 was recorded for HDLM-2, which did not accentuate despite higher concentrations of ECP. ECP97arg and ECP97thr displayed similar cytotoxicity, and the level of glycosylation did not affect cytotoxicity for HDLM-2, in contrast to the small-cell lung cancer cell-line. For EPX, no or very limited reduction in SI was seen, compared to ECP (p<0.001). The majority of cells that died from ECP (the HDLM-2 cell line) were PI positive, and only a few were annexin V positive.Conclusions ECP is cytotoxic for HRS cells, but heterogeneity between cell lines was seen. The two cell lines of B-cell origin, KMH2 and L428, were sensitive to high ECP concentrations, but for HDLM-2, of T-cell origin, the cytotoxicity reached a plateau at higher concentrations. Thus, even at presumably high concentrations, ECP can be present around HRS cells without eradicating all cells.
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| 12. |
- Hedström, Gustaf, et al.
(författare)
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Mast cell infiltration is a favourable prognostic factor in diffuse large B-cell lymphoma
- 2007
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 138:1, s. 68-71
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies indicate that the inflammatory response in diffuse large B-cell lymphomas (DLBCL) is important for the clinical outcome. Mast cells are key regulators in this response; we investigated whether the number of tryptase-positive mast cells is correlated with clinical outcome. Patients with many mast cells had a significantly better event-free survival (EFS) compared to those with few mast cells (P < 0.03 in both germinal centre (GC) and non-GC DLBCL. This supports the idea that the infiltration of mast cells is a reflection of the host inflammatory response and is related to a favourable outcome.
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| 13. |
- Lundgren, Claudia, et al.
(författare)
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Cyclin E1 is a strong prognostic marker for death from lymph node negative breast cancer : A population-based case-control study
- 2015
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 54:4, s. 538-544
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Tidskriftsartikel (refereegranskat)abstract
- Background. A large proportion of women with lymph node negative breast cancer treated with systemic adjuvant treatment do not benefit from such therapy since the patient is already cured by local treatment. Several studies have suggested that proliferation markers are strong prognostic factors in early breast cancer. Cyclins are probably the most specific markers of cell proliferation. Previously high expression of cyclin E has been associated with breast cancer recurrence.Materials and methods. In this study we investigate the prognostic value of cyclin E1 in node negative breast cancer patients. In a population-based cohort 186 women who died from breast cancer were defined as cases and 186 women alive at the corresponding time as controls. Inclusion criteria were tumour size ≤ 50 mm, no lymph node metastases and no adjuvant chemotherapy. The study was designed to detect an odds ratio of 2.5 with a power of 90% and significance level of 0.05. Cyclin E1 was determined with immunohistochemistry (IHC) on tissue microarray (TMA).Results. High expression of cyclin E1 was significantly associated with breast cancer death, in both uni- and multivariate analyses with odds ratios (OR) 2.3 [univariate, 95% confidence interval (CI) 1.5-3.6] and 2.1 (multivariate, 95% CI 1.2-3.5).Discussion. Cyclin E1 is a strong prognostic factor for breast cancer death in a population-based and node negative patient cohort and can identify high-risk patients in this group.
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| 14. |
- Löfdahl, Britta, et al.
(författare)
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Inflammatory cells in node-negative breast cancer
- 2012
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:5, s. 680-686
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Tidskriftsartikel (refereegranskat)abstract
- Background.To study the impact of inflammatory cells in a clinically well-defined cohort of women with node-negative breast cancer in a nested case-control study design.Material and methods.The cohort was comprised of 190 women who died from breast cancer and 190 women still alive at the date of death for the corresponding breast cancer patients were used as controls. The inclusion criteria included; a tumour size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy. Immunohistochemical stainings for CD3, CD4, CD8, FoxP3, CD20, tryptase and CD68 were performed on TMA blocks, evaluated and correlated to each other and to age, tumour size, histological grade, ER, PgR, Ki67 and cyclin A.Results.There was no difference regarding the amount or content of inflammatory cells in the cases compared to controls. T- and B-cells were highly correlated to each other but these cell types correlated to a lesser extent to macrophages and not at all to mast cells. A weak tendency of correlations between all the subsets of inflammatory cells and histological grade, Ki67 and cyclin A was observed, although a negative correlation was seen for mast cells.Conclusion.The amount or content of inflammatory cells in invasive breast cancer did not appear to influence death in node-negative breast cancer.
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| 15. |
- Nilsson, Cecilia, et al.
(författare)
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Molecular subtyping of male breast cancer using alternative definitions and its prognostic impact
- 2013
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 52:1, s. 102-109
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Tidskriftsartikel (refereegranskat)abstract
- Background. Male breast cancer (MBC) is an uncommon disease and there is limited information on the prognostic impact of routinely used clinicopathological parameters. Material and methods. In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stainings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event. Results. Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size andgt;20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition. Conclusion. MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC.
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| 16. |
- Niméus, Emma, et al.
(författare)
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Cyclin B1 is a prognostic proliferation marker with a high reproducibility in a population-based lymph node negative breast cancer cohort
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:4, s. 961-967
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Tidskriftsartikel (refereegranskat)abstract
- A large proportion of women with lymph node negative breast cancer treated with chemotherapy do not benefit from such treatment. Proliferation markers have been shown to recognize patients at high risk for recurrence. Ki67 has recently been included in the St Gallen guidelines. We investigated the prognostic importance of cyclin B1 in node negative breast cancer and included a study of reproducibility. In a population-based case-control study 190 women who died from breast cancer were defined as cases and 190 women alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size < 50 mm, no lymph node metastases, and no adjuvant chemotherapy. Tumor tissue was immunostained for cyclin B1. Two investigators evaluated the staining independently by counting approximately 100, 200, 500, and 1000 cells. Cyclin B1 was statistically significantly associated to breast cancer death, in both uni- and multivariate analyses (adjusted for tumor size, age, and endocrine therapy), with odds ratios 2-3 for both investigators. The agreement between the two investigators was good to very good, regardless of the number of counted cells (kappa values between 0.74 and 0.82).Cyclin B1 is a prognostic factor for breast cancer death in a population-based node negative patient cohort which can identify high-risk patients with a good to very good reproducibility. (c) 2009 UICC.
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| 17. |
- Xochelli, Aliki, et al.
(författare)
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Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations
- 2019
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Ingår i: Journal of Pathology. - : WILEY. - 0022-3417 .- 1096-9896. ; 247:4, s. 416-421
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Tidskriftsartikel (refereegranskat)abstract
- The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ-related or not; n = 65 837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non-malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments.
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| 18. |
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| 19. |
- Zhou, Wenjing, et al.
(författare)
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A Comparison of Tumor Biology in Primary Ductal Carcinoma In Situ Recurring as Invasive Carcinoma versus a New In Situ
- 2013
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Ingår i: International Journal of Breast Cancer. - : Hindawi Publishing Corporation. - 2090-3170 .- 2090-3189. ; 2013
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. About half of all new ipsilateral events after a primary ductal carcinoma in situ (DCIS) are invasive carcinoma. We studied tumor markers in the primary DCIS in relation to type of event (invasive versus in situ).Methods. Two hundred and sixty-six women with a primary DCIS from two source populations, all with a known ipsilateral event, were included. All new events were regarded as recurrences. Patient and primary tumor characteristics (estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, and Ki67) were evaluated. Logistic regression was used to calculate odd ratios and 95% confidence intervals in univariate and multivariate analyses.Results. One hundred and thirty-six of the recurrences were invasive carcinoma and 130 were in situ. The recurrence was more often invasive if the primary DCIS was ER+ (OR 2.5, 95% CI 1.2–5.1). Primary DCIS being HER2+ (OR 0.5, 95% CI 0.3–0.9), EGFR+ (OR 0.4, 95% CI 0.2–0.9), and ER95−/HER2+ (OR 0.2, 95% CI 0.1–0.6) had a lower risk of a recurrence being invasive.Conclusions. In this study, comparing type of recurrence after a DCIS showed that the ER−/HER2+ tumors were related to a recurrence being a new DCIS. And surprisingly, tumors being ER+, HER2−, and EGFR− were related to a recurrence being invasive cancer.
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| 20. |
- Zhou, Wenjing, et al.
(författare)
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Breast cancer with neoductgenesis : histopathological criteria and its correlation with mammographic and tumour features
- 2014
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Ingår i: International Journal of Breast Cancer. - : Hindawi Limited. - 2090-3170 .- 2090-3189. ; 2014
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Breast cancer with mammographic casting type calcifications, high grade DCIS with an abnormal number of ducts, periductal desmoplastic reaction, lymphocyte infiltration, and tenascin-C (TN-C) overexpression has been proposed to represent a more aggressive form of breast cancer and has been denominated as breast cancer with neoductgenesis. We developed histopathological criteria for neoductgenesis in order to study reproducibility and correlation with other tumour markers.Methods. 74 cases of grades 2 and 3 DCIS, with or without an invasive component, were selected. A combined score of the degree(s) of concentration of ducts, lymphocyte infiltration, and periductal fibrosis was used to classify cases as showing neoductgenesis, or not. Diagnostic reproducibility, correlation with tumour markers, and mammographic features were studied.Results. Twenty-three of 74 cases were diagnosed with neoductgenesis. The kappa value between pathologists showed moderate reproducibility (0.50) (95% CI; 0.41-0.60). Neoductgenesis correlated significantly with malignant type microcalcifications and TN-C expression (P = 0.008 and 0.04) and with ER, PR, and HER2 status (P < 0.00001 for all three markers).Conclusions. We developed histological criteria for breast cancer with neoductgenesis. Neoductgenesis, by our applied histopathological definition was related to more aggressive tumour biology and malignant mammographic calcifications.
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