Role of tumor size in the pre-operative management of rectal cancer patients

Clinical management of rectal cancer patients relies on pre-operative staging. Studies however continue to report moderate degrees of over/understaging as well as inter-observer variability. The aim of this study was to determine the sensitivity, specificity and accuracy of tumor size for predicting T and N stages in pre-operatively untreated rectal cancers

Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

Severe skin disease in lupus associated with hemophagocytic lymphohistiocytosis: case reports and review of the literature

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a severe clinical entity associated with high mortality in the adult population. HLH has been associated with infections, malignancy and autoimmune conditions such as Systemic Lupus Erythematosus (SLE), however this is often in the context of a disease flare. Currently, there are limited reports of inaugural SLE manifesting as HLH with a lack of consensus on treatment and management of these patients. Case presentation Here, we present two rare case reports of severe cutaneous manifestation of lupus associated with HLH. Both patients presented with sinister clinical courses with primarily rheumatologic complaints including malaise, arthralgia, and myalgia with biochemical abnormalities. Both patients were diagnosed with HLH as a result of first presentation from cutaneous lupus. A comprehensive literature review using the PubMed database with cases comprising keywords of HLH and SLE up to September 2017 was conducted, with an emphasis on inaugural cutaneous SLE cases. Conclusions Ultimately, we highlight that a keen clinical acumen is required as misdiagnosis may lead to insufficient treatment with adverse clinical outcomes with the unique presentation of HLH from inaugural cases of SLE

Urokinase-type plasminogen activator is a marker of aggressive phenotype and an independent prognostic factor in mismatch repair-proficient colorectal cancer

The aim of this study was to determine the prognostic significance of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in colorectal cancer stratified by mismatch repair status and to determine their contribution to the aggressive phenotype predicted by loss of E-cadherin and apoptosis protease activating factor-1 (APAF-1). Immunohistochemistry for uPA and uPAR was performed on a tissue microarray comprising 811 mismatch repair-proficient and 164 mismatch repair-deficient colorectal cancers. Immunoreactivity was scored semiquantitatively and the interobserver agreement between multiple pathologists was determined. Optimal cutoff scores for uPA and uPAR positivity were obtained by receiver operating characteristic curve analysis. Agreement between pathologists was excellent for uPA and uPAR. Cutoff scores of 60% for uPA and 75% for uPAR were validated by resampling of the data. In mismatch repair-proficient colorectal cancer, overexpression of uPA and uPAR was associated with advanced pT stage (P = .009, both), an infiltrating margin (P = .009 and P = .033, respectively), and poor prognosis (P = .002 and P > .001, respectively). uPA, but not uPAR, maintained its significant prognostic effect in multivariable analysis (P = .037). In addition to loss of APAF-1 (P = .002) and E-cadherin (P > .001), uPA independently predicted an infiltrating margin (P = .016). Our findings suggest that uPA, but not uPAR, is an independent prognostic factor and that this negative effect on survival is relevant specifically for mismatch repair-proficient colorectal cancers. Moreover, the combination of uPA with E-cadherin and APAF-1 is linked to an aggressive tumor phenotype and highly predictive of an infiltrating growth pattern

Tyrosine Phosphorylation of Grb2: Role in Prolactin/Epidermal Growth Factor Cross Talk in Mammary Epithelial Cell Growth and Differentiation▿

Characterizing mechanisms regulating mammary cell growth and differentiation is vital, as they may contribute to breast carcinogenesis. Here, we examine a cross talk mechanism(s) downstream of prolactin (PRL), a primary differentiation hormone, and epidermal growth factor (EGF), an important proliferative factor, in mammary epithelial cell growth and differentiation. Our data indicate that EGF exerts inhibitory effects on PRL-induced cellular differentiation by interfering with Stat5a-mediated gene expression independent of the PRL-proximal signaling cascade. Additionally, our data show that PRL is a potent inhibitor of EGF-induced cell proliferation. We identify tyrosine phosphorylation of the growth factor receptor-bound protein 2 (Grb2) as a critical mechanism by which PRL antagonizes EGF-induced cell proliferation by attenuating the activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. Together, our results define a novel negative cross-regulation between PRL and EGF involving the Jak2/Stat5a and Ras/MAPK pathways through tyrosine phosphorylation of Grb2