Assessment of programmed cell death ligand 1 (PD-L1) immunohistochemical staining is used for decision on treatment with programmed cell death 1 and PD-L1 checkpoint inhibitors in lung adenocarcinomas and squamous cell carcinomas. This study aimed to compare the staining properties of tumor cells between the antibody clones 28-8, 22C3, SP142, and SP263 and investigate interrater variation between pathologists to see if these stainings can be safely evaluated in the clinical setting. Using consecutive sections from a tissue microarray with tumor tissue from 55 resected lung cancer cases, staining with five PD-L1 assays (28-8 from two different vendors, 22C3, SP142, and SP263) was performed. Seven pathologists individually evaluated the percentage of positive tumor cells, scoring each sample applying cutoff levels used in clinical studies: <1% positive tumor cells (score 0), 1-4% (score 1), 5-9% (score 2), 10-24% (score 3), 25-49% (score 4), and >50% positive tumor cells (score 5). Pairwise analysis of antibody clones showed weighted kappa values in the range of 0.45-0.91 with the highest values for comparisons with 22C3 and 28-8 and the lowest involving SP142. Excluding SP142 resulted in kappa 0.75-0.91. Weighted kappa for interobserver variation between pathologists was 0.71-0.96. Up to 20% of the cases were differently classified as positive or negative by any pathologist compared with consensus score using ≥1% positive tumor cells as cutoff. A significantly better agreement between pathologists was seen using ≥50% as cutoff (0-5% of cases). In conclusion, the concordance between the PD-L1 antibodies 22C3, 28-8 and SP263 is relatively good when evaluating lung cancers and suggests that any one of these assays may be sufficient as basis for decision on treatment with nivolumab, pembrolizumab, and durvalumab. The scoring of the pathologist presents an intrinsic source of error that should be considered especially at low PD-L1 scores.

Semiquantitative assessment of immune markers by immunohistochemistry (IHC) has significant limitations for describing the diversity of the immune response in cancer. Therefore, we evaluated a fluorescence-based multiplexed immunohistochemical method in combination with a multispectral imaging system to quantify immune infiltrates in situ in the environment of non-small-cell lung cancer (NSCLC). A tissue microarray including 57 NSCLC cases was stained with antibodies against CD8, CD20, CD4, FOXP3, CD45RO, and pan-cytokeratin, and immune cells were quantified in epithelial and stromal compartments. The results were compared with those of conventional IHC, and related to corresponding RNA-sequencing (RNAseq) expression values. We found a strong correlation between the visual and digital quantification of lymphocytes for CD45RO (correlation coefficient: r = 0.52), FOXP3 (r = 0.87), CD4 (r = 0.79), CD20 (r = 0.81) and CD8 (r = 0.90) cells. The correlation with RNAseq data for digital quantification (0.35-0.65) was comparable to or better than that for visual quantification (0.38-0.58). Combination of the signals of the five immune markers enabled further subpopulations of lymphocytes to be identified and localized. The specific pattern of immune cell infiltration based either on the spatial distribution (distance between regulatory CD8 T and cancer cells) or the relationships of lymphocyte subclasses with each other (e.g. cytotoxic/regulatory cell ratio) were associated with patient prognosis. In conclusion, the fluorescence multiplexed immunohistochemical method, based on only one tissue section, provided reliable quantification and localization of immune cells in cancer tissue. The application of this technique to clinical biopsies can provide a basic characterization of immune infiltrates to guide clinical decisions in the era of immunotherapy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The fragmentation pattern of 30 compounds belonging to different classes of the lignan family was studied by liquid chromatography-electrospray ionization ion-trap mass spectrometry. On the basis of the observed fragmentation patterns, identification of different types of lignans was achieved. For example, dibenzylbutyrolactone lignans showed a characteristic fragmentation pathway by the loss of 44 Da (CO(2)) from the lactone moiety, whereas dibenzylbutanediols showed a loss of 48 Da by a combined loss of formaldehyde and water from the 1,4-butanediol moiety. Lignan glycosides readily lost the sugar residue to give the parent lignan as their primary product ion. In addition, several compound-specific fragmentations were observed and used for identification of individual compounds.A versatile method for analyses of lignans was developed using LC separation on a C8 column followed by fragmentation and detection of ions produced in the ion trap.

The aim was to study the perceived quality of life/life satisfaction in a sample of women with breast cancer who were treated in a hospital with alternative/complementary care and the same variables in individually matched patients who received only conventional medical treatment. A non-randomized controlled trial design with repeated measurements was used. Sixty women with breast cancer treated with anthroposophic medicine (ABCW) and 60 with conventional medicine (CBCW) were included and 36 matched pairs took part on all occasions. The quality of life was measured by the EORTC QLQ-C30 and the Life Satisfaction Questionnaire (LSQ). The comparisons were calculated as effect sizes (ES). The women in the ABCW group reported small or moderate effects, expressed as ES, on their quality of life/life satisfaction compared to their matched "twins" in the CBCW group at the 1-year follow-up in 15 out of 21 scales/factors. It was concluded that the women who had chosen anthroposophic care increased their perceived quality of life/life satisfaction according to the methodology of the study.

The aim of the present study, which is part of a major clinical controlled study of the life situation of women with breast cancer, was to compare two groups of women concerning perceived quality of life and coping. The women were treated in two different cancer treatment programs: complementary treatment, which included anthroposophic therapy, and conventional cancer treatment. A total of 120 women were included, 60 women treated with anthroposophic medicine, and 60 individually matched women treated with conventional medicine only. Quality of life was measured by the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Core 30, and the Life Satisfaction Questionnaire. Coping was measured by the Mental Adjustment to Cancer scale. The results showed that the women who chose anthroposophic therapy perceived their quality of life to be lower on admission to the hospital and showed more anxious preoccupation than the women in conventional medicine. It can be concluded that, due to the careful matching procedure, the women in the two groups are comparable in a medical sense but not from the perspective of quality of life and coping.