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- Mansour, Mohammed S.I., et al.
(författare)
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Determination of PD-L1 expression in effusions from mesothelioma by immuno-cytochemical staining
- 2017
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Ingår i: Cancer Cytopathology. - : Wiley. - 1934-662X .- 1934-6638. ; 125:12, s. 908-917
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDMalignant mesothelioma (MM) is an aggressive, fatal tumor. Current therapeutic options only marginally improve survival. Programmed cell death ligand 1 (PD-L1) is a dominant mediator of immunosuppression, binding to programmed cell death 1 (PD-1). PD-L1 is up-regulated in cancer cells, and the PD-1/PD-L1 pathway plays a critical role in tumor immune evasion, thus providing a target for antitumor therapy. Further, a correlation between PD-L1 expression and prognosis has been reported. Studies performed on histological material have revealed expression of PD-L1 in MM, but no study has been performed on MM effusions thus far. METHODSPD-L1 expression was determined by a commercially available antibody (clone 28-8) in 74 formalin-fixed, paraffin-embedded cell blocks from body effusions obtained at diagnosis from patients with MM. The presence of MM cells was confirmed with CK5/6, calretinin, and EMA and the admixture of macrophages was assessed with CD68. Only cases containing more than 100 tumor cells were assessed. Membranous staining in tumor cells was considered positive. Survival time was calculated from the appearance of the first malignant effusion until death. RESULTSReactivity was observed in 23 of 61 (38%) of cases and was classified as 1%-5% (n = 9 cases), >5%-10% (n = 4 cases), >10%-50% (n = 4 cases), and >50% (n = 6 cases) positive cells. Survival times did not differ significantly between patients with PD-L1-positive and PD-L1-negative tumors. CONCLUSIONMM effusions are suitable for immune-cytochemical assessment of PD-L1 expression in malignant cells and the results are similar to those reported for histological specimens. Cancer Cytopathol 2017;125:908-17. (c) 2017 American Cancer Society. We studied the PD-L1 reactivity of tumor cells in 74 formalin-fixed, paraffin-embedded cell blocks from body effusions obtained at diagnosis from 74 patients with malignant mesothelioma. In 61 cases, the PD-L1 reactivity could be soundly determined, and the number of positive cases agrees with the outcomes of other studies performed on histological material, suggesting the determination of PD-L1 status in effusions as an early and convenient alternative.
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- Mansour, Mohammed S.I., et al.
(författare)
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Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer
- 2021
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Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- PD-L1 expression assessed by immunohistochemical staining is used for the selection of immunotherapy in non-small cell lung cancer (NSCLC). Appropriate validation of PD-L1 expression in cytology specimens is important as cytology is often the only diagnostic material in NSCLC. In a previous study comprising two different cohorts of paired biopsies and cytological specimens, we found a fairly good cyto-histological correlation of PD-L1 expression in one, whereas only a moderate correlation was found in the other cohort. Therefore, that cohort with additional new cases was now further investigated for the impact of preanalytical factors on PD-L1 concordance in paired biopsies and cytological specimens. A total of 100 formalin-fixed paraffin-embedded cell blocks from 19 pleural effusions (PE), 17 bronchial brushes (BB), and 64 bronchoalveolar lavage (BAL) and concurrent matched biopsies from 80 bronchial biopsies and 20 transthoracic core biopsies from NSCLC patients were stained using the PD-L1 28-8 assay. Using the cutoffs & GE;1%, & GE;5%, & GE;10%, and & GE;50% positive tumour cells, the overall agreement between histology and cytology was 77-85% (kappa 0.51-0.70) depending on the applied cutoff value. The concordance was better for BALs (kappa 0.53-0.81) and BBs (kappa 0.55-0.85) than for PEs (kappa -0.16-0.48), while no difference was seen for different types of biopsies or histological tumour type. A high number of tumour cells (> 500) in biopsies was associated with better concordance at the & GE;50% cutoff. In conclusion, the study results suggest that PEs may be less suitable for evaluation of PD-L1 due to limited cyto-histological concordance, while a high amount of tumour cells in biopsies may be favourable when regarding cyto-histological PD-L1 concordance.
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- Skírnisdóttir, Ingiridur, 1951-, et al.
(författare)
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A new prognostic model comprising p53, EGFR, and tumor grade in early stage epithelial ovarian carcinoma and avoiding the problem of inaccurate surgical staging
- 2004
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Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 14:2, s. 259-270
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial ovarian carcinoma rarely occurs because of a single event. Therefore, no single biological tumor factor will give accurate prognostic information for all ovarian cancer patients. On the other hand, a combination of two or more independent factors may yield an improved overall prognostic index. Because FIGO stage is included in most of the previously presented models, inaccurate surgical staging in patients with apparently early disease has been a problem. In a series of 226 patients with epithelial ovarian carcinomas in FIGO stages IA-IIC, a number of clinicopathological factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to the biological factors p53 and epidermal growth factor receptor (EGFR), important regulators of the apoptosis and mitosis. Immunohistochemical techniques were used. All patients received adjuvant radiotherapy or chemotherapy after the primary surgery. Expression of p53 was significantly associated with the tumor grade and disease-free survival (DFS). EGFR expression was also associated with DFS. In a Cox multivariate analysis, tumor grade, p53 status, and EGFR status were all independent and significant prognostic factors with regard to DFS. A prognostic model was proposed using these factors. A low-risk group, an intermediate-risk group, and a high-risk group were defined. DFS amounted to 89% in the low-risk group (grades 1-2, p53-negative, and EGFR-negative), 66% in the intermediate-risk group (grade 3, p53-negative, and EGFR-negative or grades 1-2, p53-positive or EGFR-positive) and 39% in the high-risk group (grade 3, p53-positive, and EGFR-positive).
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- Skírnisdóttir, Ingiridur, 1951-, et al.
(författare)
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The apoptosis regulators p53, bax and PUMA : Relationship and impact on outcome in early stage (FIGO I-II) ovarian carcinoma after post-surgical taxane-based treatment
- 2012
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 27:3, s. 741-747
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate the prognostic effect of the apoptosis regulators p53, bax and PUMA for recurrent disease and disease-free survival (DFS) in a series of 105 patients in FIGO-stages I-II with epithelial ovarian cancer, all treated with post-surgical platinum-taxane chemotherapy. For the detection of positivity of the biological markers p53, bax and PUMA the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of p53 positivity was 24%, that of bax positivity was 83%, and strong positivity was found for PUMA (43%). The bax status was related to tumor grade (P=0.029). Positive staining for bax was related to strong positivity of PUMA in the tumors (P=0.004). The p53, bax or PUMA status alone or concomitant (p53 bax, p53 PUMA and bax PUMA) were not related to age, histopathological subtype, serous/non-serous tumors or type of the staging procedure at primary surgery. In survival analysis p53-positive tumors (P=0.014) and concomitant p53-positive and weak PUMA-positive tumors (P=0.015) were significantly correlated with shorter DFS. Concomitant p53-negative and bax-positive tumors were significantly correlated with longer survival (P=0.019). FIGO-stage (OR=6.0) and p53 status (OR=4.1) were predictive factors for tumor recurrence in logistic regression analysis and independent prognostic factors (HR=2.4 for both) in multivariate Cox regression analysis. In a separate Cox multivariate regression analysis the p53 bax status (HR=2.2) was an independent prognostic factor for DFS. The p53 PUMA status (HR=0.4) was not an independent prognostic factor, however, a borderline significance (P=0.07) was noted. Our results indicate that FIGO stage and p53 status alone were independent predictive factors for recurrence and prognostic factors for survival. Furthermore, p53 bax status was an independent prognostic factor for survival in this study.
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