Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups

Background: Special AT-rich sequence-binding protein 2 (SATB2) has emerged as an alternative immunohistochemical marker to CDX2 for colorectal differentiation. However, the distribution and prognostic relevance of SATB2 expression in colorectal carcinoma (CRC) have to be further elucidated. Methods: SATB2 expression was analysed in 1039 CRCs and correlated with clinicopathological and morphological factors, CDX2 expression as well as survival parameters within the overall cohort and in clinicopathological subgroups. Results: SATB2 loss was a strong prognosticator in univariate analyses of the overall cohort (p < 0.001 for all survival comparisons) and in numerous subcohorts including high-risk scenarios (UICC stage III/high tumour budding). SATB2 retained its prognostic relevance in multivariate analyses of these high-risk scenarios (e.g., UICC stage III: DSS: p = 0.007, HR: 1.95), but not in the overall cohort (DSS: p = 0.1, HR: 1.25). SATB2 loss was more frequent than CDX2 loss (22.2% vs. 10.2%, p < 0.001) and of higher prognostic relevance with only moderate overlap between SATB2/CDX2 expression groups. Conclusions: SATB2 loss is able to identify especially aggressive CRCs in high-risk subgroups. While SATB2 is the prognostically superior immunohistochemical parameter compared to CDX2 in univariate analyses, it appears to be the less sensitive marker for colorectal differentiation as it is lost more frequently.

Effect of Coronary Disease Characteristics on Prognostic Relevance of Residual Ischemia After Stent Implantation

Objectives: We investigated the influence of coronary disease characteristics on prognostic implications of residual ischemia after coronary stent implantation.Methods: This study included 1,476 patients with drug-eluting stent implantation and available pre- and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) measurements. Residual ischemia was defined as post-PCI FFR ≤ 0.80. Coronary disease characteristics with significant interaction hazard ratios (HRs) for clinical outcomes with residual ischemia were defined as interaction characteristics with residual ischemia (ICwRI). The primary outcome was target vessel failure (TVF)—a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization—at 2 years.Results: The mean pre- and post-PCI FFR were 0.68 ± 0.11 and 0.87 ± 0.07, respectively. During the median follow-up duration of 2.0 years, the cumulative incidence of TVF was 6.1%. The 203 vessels (13.8%) with residual ischemia had higher risks of TVF compared to that for post-PCI FFR &gt;0.80 (P &lt; 0.001). ICwRI with a significant interaction HR with residual ischemia included pre-PCI SYNTAX score &gt;17 and pre-PCI FFR ≤ 0.62. Each ICwRI had a direct prognostic effect not mediated by residual ischemia. The association between an increased TVF risk and residual ischemia was significant in patients with 0 or 1 ICwRI [hazard ratio (HR) 3.25, 95% confidence interval (CI) 1.90–5.57, P &lt; 0.001] but not in those with 2 ICwRI (HR 0.47, 95% CI 0.14–1.64, P = 0.24). Among patients with post-PCI FFR &gt;0.80, those with 2 ICwRI showed similar TVF risks to those with residual ischemia (HR 1.55, 95% CI 0.79–3.02, P = 0.20).Conclusions: Coronary disease characteristics including pre-PCI SYNTAX score and pre-PCI FFR affected the prognostic implications of residual ischemia. The prognostic relevance of residual ischemia was attenuated in patients with multiple interacting characteristics.

Prognostic Relevance of BRCA1 Expression in Survival of Patients With Cervical Cancer

ObjectiveBRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in several cancers, the objective of this study was to investigate BRCA1 expression using immunohistochemistry (IHC) in cervical cancer and its possible prognostic relevance.MethodsSeventy patients with cervical cancer were enrolled in this study. Samples from each tumor were stained for BRCA1 and reviewed independently by gynecologic pathologists blinded to the BRCA status. Kaplan–Meier methods were used to estimate overall survival according to BRCA1 expression. Differentially expressed genes (DEGs) by BRCA1 expression were selected using GSE44001 dataset, which included 300 samples treated with radical hysterectomy. In addition, cox regression analysis with backward elimination was performed to select independent prognostic markers. Gene set enrichment analysis (GSEA) was done using these DEGs.ResultsBRCA1 IHC was positive in 62.9% (44/70) of cases. Patients with BRCA1 expression showed better overall survival (100% vs. 76.2%, HR 0.20, 95% CI 0.04 – 0.99, p = 0.028) than those without BRCA1 expression. Analysis of gene expression profiles according to BRCA1 expression identified 321 differentially expressed mRNAs. Gene set enrichment analysis results showed two dysregulated pathways (VEGF_A_UP.V1_DN and E2F1_UP.V1_UP). Of these DEGs, alterations of 20 gene signatures were found to be independently associated with survival outcomes of patients.ConclusionsBRCA1 expression in cervical cancer tissue is associated with survival. In addition, the identification of specific gene alterations associated with BRCA1 expression could help to provide individualized prediction in these patients.