35 research outputs found

    PD-L1 expression and type-I interferon response in non-small cell lung cancer

    No full text
    Background &amp; objective: PD-1/PD-L1 inhibitors represents a breakthrough in the treatment of non-small cell lung cancer (NSCLC), but there are significant differences in treatment effectiveness, even in PD-L1-positive tumors. PD-L1 expression can be attributed to several factors, including a response to type-I interferon, which generally has many anti-tumor effects. The purpose of this study was to investigate the relationship between PD-L1 expression and type-I interferon response in lung carcinomas.Methods: We examined the immunohistochemical expression of PD-L1 and MxA (type-I interferon-stimulated gene) in tissue microarrays with 106 different NSCLC cases, assessed by both the percentage of positive tumor cells (TPS) and H-score (0-300).Results: No correlation was found between PD-L1 and MxA, either as TPS vs H-score (R²=0.06), or in treatment-relevant categories (&lt;1%, 1-24%, 25-49%, 50%-) that apply in Denmark. 7 out of 16 cases with TPS&gt;50% were MxA-negative.Conclusions: We found no correlation between type-I interferon response and PD-L1 expression in NSCLC. The identification of a group of patients with high PD-L1 expression but without type-I interferon response may suggests a potentially beneficial effect of interferon-stimulating treatments for this subset of NSCLC patients, but further investigation is required.<br/

    Internal quality control in an academic cytopathology laboratory for the introduction of a new reporting system for endometrial cytology

    No full text
    Background: To evaluate reproducibility of a reporting system for endometrial cytology. Methods: Cytologic slides from 49 patients, prepared via liquid based cytology, were blindly examined by five cytopathologists of various experience levels, applying a recently introduced reporting system as previously reported. The agreement among cytopathologists was evaluated via Kappa (κ) statistics and the Kendall's Coefficient of Variation (W); cytologic results were compared with the relevant histologic report. Results: Substantial agreement among all five raters was found in the benign, ACE-L and malignant categories, fair agreement in inadequate and ACE-H categories, whereas only slight agreement in ACE-U. For the three more experienced cytopathologists, an almost perfect agreement was found in inadequate, benign, and ACE-L categories, substantial agreement in ACE-H and malignant categories and fair agreement in ACE-U category. Overall agreement for all five cytopathologists and for all categories was moderate, whereas it was very high for the three senior raters. Using the Kendall's test, both five cytopathologists (W = 0.81) and the three senior ones (W = 0.93) had very high agreement. Sensitivity: 83.33–92.59%, specificity: 83.33–94.74%, ROC area: 71.72–90.3%. Conclusion: Application of appropriate statistical tests shows that integration of a new reporting cytologic system is effective with an overall accuracy around 90%. Both statistical tests applied disclosed lower agreement rates among both all five raters and the three most experienced ones in the intermediate categories constituting the gray zone, thus delineating the need for better training of cytopathologists to correctly identify diagnostic criteria for classification of a given case into these categories.</p

    Promoter Methylation of p16 INK4A , hMLH1, and MGMT in Liquid-Based Cervical Cytology Samples Compared with Clinicopathological Findings and HPV Presence

    No full text
    Cervical cancer is a common cancer inflicting women worldwide. Even though, persistent infection with oncogenic Human Papillomavirus (HPV) types is considered the most important risk factor for cervical cancer development, less than 5% of women with HPV will eventually develop cervical cancer supporting that other molecular events, like methylation-dependent inactivation of tumor suppressor genes, may cocontribute in cervical carcinogenesis. We analyzed promoter methylation of three candidate genes (p16, MGMT, and hMLH1) in 403 liquid-based cytology samples. Methylation was commonly identified in both benign and pathologic samples and correlated with higher lesion grade determined by cytological, colposcopical, or histological findings, with HPV DNA and mRNA positivity of specific HPV types and p16 INK4A protein expression. Overall accuracy of methylation is much lower than traditional diagnostic tests ranking it as an ancillary technique with more data needed to identify the exact value of methylation status in cervical carcinogenesis

    Promoter Methylation of p16<sup>INK4A</sup>, hMLH1, and MGMT in Liquid-Based Cervical Cytology Samples Compared with Clinicopathological Findings and HPV Presence

    No full text
    Cervical cancer is a common cancer inflicting women worldwide. Even though, persistent infection with oncogenic Human Papillomavirus (HPV) types is considered the most important risk factor for cervical cancer development, less than 5% of women with HPV will eventually develop cervical cancer supporting that other molecular events, like methylation-dependent inactivation of tumor suppressor genes, may cocontribute in cervical carcinogenesis. We analyzed promoter methylation of three candidate genes (p16, MGMT, and hMLH1) in 403 liquid-based cytology samples. Methylation was commonly identified in both benign and pathologic samples and correlated with higher lesion grade determined by cytological, colposcopical, or histological findings, with HPV DNA and mRNA positivity of specific HPV types and p16INK4Aprotein expression. Overall accuracy of methylation is much lower than traditional diagnostic tests ranking it as an ancillary technique with more data needed to identify the exact value of methylation status in cervical carcinogenesis.</jats:p
    corecore