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Sökning: WFRF:(Fjällskog Marie Louise)

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  • Föregående 12[3]4567Nästa
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  • Zhou, Wenjing, et al. (författare)
  • A Comparison of Tumor Biology in Primary Ductal Carcinoma In Situ Recurring as Invasive Carcinoma versus a New In Situ
  • 2013
  • Ingår i: International Journal of Breast Cancer. - 2090-3170 .- 2090-3189. ; 2013, s. 582134
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Introduction</p><p>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).</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p>
  • Zhou, Wenjing, et al. (författare)
  • Breast cancer with neoductgenesis : histopathological criteria and its correlation with mammographic and tumour features
  • 2014
  • Ingår i: International Journal of Breast Cancer. - 2090-3170 .- 2090-3189. ; 2014
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p><p>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.</p><p>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 &lt; 0.00001 for all three markers).</p><p>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.</p>
  • Zhou, Wenjing, 1979-, et al. (författare)
  • Breast carcinoma with neoductgenesis : a new subgroup of breast cancer
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • <p>Background: A new subgroup of breast cancer has been proposed: breast carcinoma with neoductgenesis. Cases presenting with casting type calcifications on the mammogram, histologically high grade DCIS with an abnormal number of ducts, periductal desmoplastic reaction and lymphocyte infiltration has been suggested to represent a more aggressive form of breast cancer. Treatment decision based on traditional histopathology showing DCIS might be challenged if neoductgenesis is diagnosed. We evaluated a histological classification system proposed for neoductgenesis and studied tumor biology in cases with and without neoductgenesis.</p> <p> </p> <p>Material and Method: Seventy-four tumors with DCIS grade 2-3, with or without an invasive component, were blocked in TMAs. A classification system based on a pathological evaluation and Tenascin-C (Tn-C) expression was used to categorize tumors as showing neoductgenesis or not. Immunohistochemical staining for known tumor markers and correlation with mammographic features was performed. Logistic regression model was use to evaluate the correlation between breast carcinoma with neoductgenesis and molecular- and mammographic features.</p> <p> </p> <p>Results: Four pathologists could categorize cases as “possible neoductgenesis” with an overall correlation of 72% and a kappa value of 0.44. Adding Tn-C staining resulted in a group with neoductgenesis (n=37) and one without (n=31). Neoductgenesis correlated significantly with mammographic casting- and crushed stone microcalcifications and estrogen receptor status (p-values 0.04 and 0.03, respectively). High nuclear grade, HER2 positivity, progesterone receptor negativity and high proliferation were also more often seen in the group with neoductgenesis, but this was not statistically significant (0.10, 0.07, 0.20 and 0.29).</p> <p> </p> <p>Discussion: We developed reproducible histologic criteria for a new entity: breast carcinoma with neoductgenesis. The system seemed to be useful in receiving reproducibility between pathologists making the diagnosis. Neoductgenesis was related to more aggressive tumor biology and to the mammographic features. Our findings have to be repeated and the relation to prognosis further studied. However, we can already predict a potential benefit for women earlier considered having a pure DCIS but now diagnosed as breast carcinoma with neoductgenesis and a need to develop appropriate treatment regiments.</p>
  • Zhou, Wenjing, et al. (författare)
  • Molecular subtypes in ductal carcinoma in situ of the breast and their relation to prognosis a population-based cohort study
  • 2013
  • Ingår i: BMC Cancer. - 1471-2407 .- 1471-2407. ; 13, s. 512
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Different molecular subtypes of breast cancer have been identified based on gene expression profiling. Treatment suggestions based on an approximation of these subtypes by immunohistochemical criteria have been published by the St Gallen international expert consensus panel. Ductal carcinoma in situ (DCIS) can be classified into the same molecular subtypes. Our aim was to study the relation between these newly defined subtypes and prognosis in DCIS.</p><p><strong>METHODS:</strong> TMA including 458 women from a population-based cohort with DCIS diagnosed 1986-2004 was used. Stainings for ER, PR, HER2 and Ki67 were used to classify the surrogate molecular subtypes according to the St Gallen criteria from 2011. The associations with prognosis were examined using Kaplan-Meier analyses and Cox proportional hazards regression models.</p><p><strong>RESULTS:</strong> Surrogate molecular subtyping could be done in 381 cases. Mean follow up was 164 months. Of the classified DCIS 186 were Luminal A (48.8%), 33 Luminal B/HER2- (8.7%), 74 Luminal B/HER2+ (17.4%), 61 HER2+/ER- (16.0%) and 27 Triple Negative (7.1%). One hundred and two women had a local recurrence of which 58 were invasive. Twenty-two women had generalised disease, 8 without a prior local recurrence. We could not find a prognostic significance of the molecular subtypes other than a higher risk of developing breast cancer after more than 10 years of follow-up among women with a Triple Negative DCIS (OR 3.2; 95% CI 1.1-9.8).</p><p><strong>CONCLUSIONS:</strong> The results from this large population-based cohort, with long-term follow up failed to demonstrate a prognostic value for the surrogate molecular subtyping of DCIS using the St Gallen criteria up to ten years after diagnosis. More than ten years after diagnosis Triple Negative DCIS had an elevated risk of recurrence.</p>
  • Zhou, Wenjing, et al. (författare)
  • Tumor Markers Predicting Type of Recurrence after a Primary Ductal Carcinoma <em>In Situ</em>
  • 2012
  • Ingår i: Breast Cancer Research. - 1465-5411 .- 1465-542X.
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • <p><strong>Introduction: </strong></p> <p>About half of all recurrences after a primary ductal carcinoma <em>in situ</em> (DCIS) are invasive. The determinants for type of recurrence, in situ or invasive, are not known. We studied markers in primary DCIS in relation to type of recurrence.</p> <p><strong>Methods:</strong></p> <p>Two hundred and sixty six primary DCIS with a known recurrence were included. One hundred were from a population based cohort with 458 women diagnosed 1986-2004 in Uppland/Västmanland region, Sweden, and all 166 women with a recurrence from the randomized nationwide SweDCIS Trial (1987-1999). The 358 women without a recurrence were used as a reference group. TMA-blocks were constructed and estrogen receptor- (ER), progesterone receptor- (PR), HER2, EGFR, cytokeratin 5/6, Ki67, FOXA1, FOXC1, GATA-3 and CD10 status were evaluated in the primary tumors. Logistic regression was used to calculate odd ratios and 95% confidence intervals in univariate and multivariate analyses (adjusted for age, free margin, surgical method and molecular subtype).</p> <p><strong>Results:</strong></p> <p>One hundred and thirty of the recurrences were <em>in situ</em> and 136 invasive. In multivariate analyses, a recurrence was more often invasive if the primary was ER positive (OR 2.5, CI 95 1.2 – 5.1). Primaries being HER2 positive (OR 0.5, CI 95 0.3-0.9), EGFR positive (OR 0.4, CI 95 0.2-0.9) and ER-/HER2+ (OR 0.2, CI 95 0.1-0.6) had a lower risk of the recurrence being invasive. Primaries of the molecular subtype ER+/HER2+ had higher risk of any recurrence (OR 1.9, CI 95 1.1-3.4) as did primaries expressing FOXA1 (OR 3.1, CI 95 1.5-6.2) and FOXC1 (OR 2.9, CI 95 1.7-5.0).</p> <p><strong>Conclusions:</strong></p> <p>Surprisingly, recurrences after an ER-/HER2+, ER negative or EGFR positive primary DCIS were more often of the <em>in situ type</em>. The molecular subtype ER+/HER2+, FOXA1 positivity and FOXC1 positivity were risk factors for any recurrence.</p>
  • Ahlin, Cecilia, et al. (författare)
  • Aberrant expression of cyclin E in low-risk node negative breast cancer
  • 2008
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 47:8, s. 1539-1545
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><em>Background.</em> Cyclin E is a cell cycle regulatory protein which occurs in G1, peaks in late G1 and is degraded in early S-phase. Cyclin E overexpression appears to be an independent prognostic factor for overall survival in breast cancer. <em>Material and Methods.</em> Nuclear cyclin A is a reliable marker for S-and G2-phases. Consequently, aberrant expression of cyclin E can be detected by simultaneous immunostainings for cyclin A and cyclin E. Studies have shown that aberrant cyclin E might provide additional prognostic information compared to that of cyclin E alone. This study aimed to investigate cyclin E and aberrant cyclin E expression in low-risk node negative breast cancer. We compared women that died from their breast cancer (n=17) with women free from relapse&gt;8 years after initial diagnosis (n=24). All women had stage I, low risk breast cancer. The groups were matched regarding tumour size, receptor status, adjuvant chemotherapy and tumour differentiation. Tumour samples were analysed regarding expression of cyclin A, cyclin E and double-stained tumour cells using immunoflourescence staining and digital microscopy. <em>Results.</em> No differences were seen regarding expression of cyclin E or aberrant cyclin E in cases compared to controls. <em>Discussion.</em> We conclude that neither cyclin E nor aberrant cyclin E is a prognostic factor in low-risk node negative breast cancer patients.</p>
  • Ahlin, Cecilia, 1966- (författare)
  • Cyclin A and cyclin E as prognostic factors in early breast cancer
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Breast cancer is one of the most common malignancies in women. Due to early detection and the use of screening programs approximately 60% of all new cases lack lymph node involvement. Today, a substantial proportion of these women will be offered adjuvant systemic chemotherapy. However, better proliferation markers are needed to predict patient outcome and to avoid overtreatment. </p><p>Cyclin A, cyclin E and Ki-67 are all markers for proliferation and involved in the regulation of the cell cycle. Overexpression has been associated with disease recurrence in several studies, but the results have not been consistent. However, none of these studies has investigated aberrant expression of cyclin E (the expression of cyclin E during phases of the cell cycle other than late G1 and early S-phase). Studies have shown that aberrant cyclin E might provide additional prognostic information compared to cyclin E alone.</p><p>The aims of this thesis were 1.to investigate the prognostic value of cyclin A, cyclin E and aberrant cyclin E in early breast cancer. 2.to validate the tissue microarray (TMA) technique for cyclin A and 3.to define the most optimal cut-off values for cyclin A and Ki-67.</p><p>We found that the agreement of TMA and large section results was good with kappa values 0.62-0.75 and that the reproducibility of the two readers’ results was good or even very good, with kappa values 0.71 – 0.87. </p><p>The optimal cut-off value for cyclin A average was 8% and for cyclin A maximum value 11%. The corresponding values for Ki-67 were 15 and 22%. </p><p>Neither cyclin E nor aberrant cyclin E was a prognostic factor in low-risk node negative breast cancer patients. </p><p>Finally, we conclude that cyclin A is a prognostic factor in node negative breast cancer (univariate analysis average value OR=2.9 95% CI 1.8-4.6; maximum value OR=3.7 95% CI 2.3-5.9).</p>
  • Ahlin, Cecilia, et al. (författare)
  • High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers
  • 2017
  • Ingår i: Breast Cancer Research and Treatment. - SPRINGER. - 0167-6806 .- 1573-7217. ; 164:3, s. 667-678
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Cyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to validate this differential ER-related effect and furthermore explore the relationship between cyclin D overexpression and CCND1 gene amplification status in a node-negative breast cancer case-control study. Immunohistochemical nuclear expression of cyclin D1 (n = 364) and amplification of the gene CCND1 by fluorescent in situ hybridization (n = 255) was performed on tissue microarray sections from patients with T1-2N0M0 breast cancer. Patients given adjuvant chemotherapy were excluded. The primary event was defined as breast cancer death. Breast cancer-specific survival was analyzed in univariate and multivariable models using conditional logistic regression. Expression of cyclin D1 above the median (61.7%) in ER breast cancer was associated with an increased risk for breast cancer death (OR 3.2 95% CI 1.5-6.8) also when adjusted for tumor size and grade (OR 3.1). No significant prognostic impact of cyclin D1 expression was found among ER-negative cases. Cyclin D1 overexpression was significantly associated to high expression of the proliferation markers cyclins A (rho 0.19, p = 0.006) and B (rho 0.18, p = 0.003) in ER-positive tumors, but not in ER-negative cases. There was a significant association between CCND1 amplification and cyclin D1 expression (p = 0.003), but CCND1 amplification was not statistically significantly prognostic (HR 1.4, 95% CI 0.4-4.4). We confirmed our previous observation that high cyclin D1 expression is associated to high proliferation and a threefold higher risk of death from breast cancer in ER-positive breast cancer.</p>
  • Deb, Siddhartha, et al. (författare)
  • Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer
  • 2014
  • Ingår i: Modern Pathology. - 0893-3952 .- 1530-0285. ; 27:9, s. 1223-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1 alpha (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.</p>
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  • Föregående 12[3]4567Nästa
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