Real-life evaluation of histologic scores for Ulcerative Colitis in remission.

BACKGROUND: Histological evaluation of ulcerative colitis (UC) patients has been debated ever since the first description of the disease and its role in follow-up has never been fully established. Recent evidence suggests an added benefit in accuracy when evaluating if the patient is in remission. Unfortunately, there are several different histological indices, and it is difficult to compare outcomes where different scores are applied. Histopathological evaluation is prone to subjective biases, despite the use of indices. In addition, these indices are developed by expert IBD pathologist, but applied at large, by general pathologist. Therefore, we evaluated the three most applied histological indices for UC on samples from patients in remission to compare test qualities and estimate their usefulness to identify remission by both general and GI specialized pathologist. METHOD: Mucosal biopsies from 41 UC patients in clinical and endoscopic remission were collected as part of a larger study on UC. Three pathologists blinded to the patients' clinical status evaluated them using Geboes score (GS), Nancy Index (NI) and Robarts Histopathological Index (RHI). We calculated the agreement between the pathologists using Inter-class correlation (ICC) and visualized it with ICC-plots and Bland-Altman plots. Association between clinical factors and histological category were analysed by Fisher's exact test. RESULTS: The ICC value for GS, RHI and NI were 0.85, 0.73 and 0.70 respectively. The limits of agreement were ±6.1, ±4.0 and ±1.4, for GS, RHI and NI, respectively. Mayo endoscopic subgrade and UC clinical score did not show association with any histological scores. Despite clinical and endoscopic remission 7-35% of the patients displayed histological inflammation on a level classified as active disease, depending on the index and cut-off. CONCLUSION: A substantial amount of UC patients in clinical and endoscopic remission display inflammation on a histological level, but the ability to classify these patients accurately and consistently could be improved.

Evaluation of tumor-infiltrating lymphocytes using routine H&E slides predicts patient survival in resected non-small cell lung cancer.

The presence of tumor-infiltrating lymphocytes (TILs) positively impacts the outcome of non-small cell lung cancer (NSCLC) patients. Most previous studies have assessed TILs using different immunohistochemical assays. The purpose of this study was to develop and validate a histopathological scoring model for the assessment of TILs in whole-tissue hematoxylin and eosin (H&E)-stained section slides of NSCLC patients and to evaluate the model in an immunoscore setting. Therefore, TIL was evaluated manually on H&E slides from 537 surgical specimens of primary resected stage I-III NSCLC patients. Using stromal TIL score as a stepwise discrete variable, increasing survival was seen with rising TIL level: disease-specific survival (DSS; P = .008), overall survival (P = .036) and disease-free survival (P = .006). Subgroup analysis revealed that high stromal TILs level was associated with superior DSS (P = .047) in patients with squamous cell carcinoma, but not in patients with adenocarcinoma. Multivariable analysis confirmed that high TIL levels independently predict improved prognosis for all endpoints in the overall cohort. In conclusion, high stromal TIL level is an independent favorable prognostic factor in stage I-III NSCLC patients. The comprehensive histological evaluation conducted in this study may be helpful in streamlining TIL quantification for routine clinical use in a future NSCLC immunoscore setting.

Expression and function of the miR-143/145 cluster in vitro and in vivo in human breast cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators of gene expression and are dysregulated in cancer. Studies of miRNAs to explore their potential as diagnostic and prognostic markers are of great scientific interest. Here, we investigate the functional properties and expression of the miR-143/145 cluster in breast cancer (BC) in vitro and in vivo. The ER positive MCF7, the HER2 positive SK-BR-3, and the triple negative cell line MDA-MB-231 were used to assess cell proliferation and cell invasion. Expression of miRNA in 108 breast cancers in the Norwegian Women and Cancer Study and 44 benign tissue controls were analyzed by microarray and validated by RT-PCR. Further, in situ hybridization (ISH) was used to study the cellular and subcellular distribution of the miRNAs. In vitro, miR-143 promoted proliferation of MCF7 and MDA-MB-231 cells, whereas miR-145 and the cotransfection of both miRNAs inhibited proliferation in all three cell lines. The cells' invasive capacity was reduced after transfection and cotransfection of the miRNAs. In line with the tumor suppressive functions in vitro, the expression of miR-143 and miR-145 was lower in malignant compared to benign breast tissue, and lower in the more aggressive tumors with higher tumor grade, loss of ER and the basal-like phenotype. ISH revealed miR-143 to be cytoplasmatic and predominantly expressed in luminal cells in benign tissue, whilst miR-145 was nuclear and with strong staining in myoepithelial cells. Both miRNAs were present in malignant epithelial cells and stromal fibroblasts in BC. This study demonstrates that miR-143 and -145 have functional properties and expression patterns typical for tumor suppressors, but the function is influenced by cellular factors such as cell type and miRNA cotransfection. Further, the nuclear functions of miR-145 should be explored for a more complete understanding of the complexity of miRNA regulation and function in BC.