The Role of FBXW7 in Gynecologic Malignancies.

The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial component of the Skp1-Cullin1-F-box (SCF) complex, which is a ubiquitin ligase. This complex aids in the degradation of many oncoproteins, such as cyclin E, c-JUN, c-MYC, NOTCH, and MCL1, via the ubiquitin-proteasome system (UPS). The FBXW7 gene is commonly mutated or deleted in numerous types of cancer, including gynecologic cancers (GCs). Such FBXW7 mutations are linked to a poor prognosis due to increased treatment resistance. Hence, detection of the FBXW7 mutation may possibly be an appropriate diagnostic and prognostic biomarker that plays a central role in determining suitable individualized management. Recent studies also suggest that, under specific circumstances, FBXW7 may act as an oncogene. There is mounting evidence indicating that the aberrant expression of FBXW7 is involved in the development of GCs. The aim of this review is to give an update on the role of FBXW7 as a potential biomarker and also as a therapeutic target for novel treatments, particularly in the management of GCs.

Staphylococcus Infection-Associated GN - Spectrum of IgA Staining and Prevalence of ANCA in a Single-Center Cohort.

BACKGROUND AND OBJECTIVES: Staphylococcus infection-associated GN (SAGN) is a well recognized disease entity, particularly because of the frequent IgA-dominant glomerular immunoglobulin staining on kidney biopsy. Biopsy features can resemble two other disease entities - primary IgA nephropathy and Henoch-Schönlein purpura nephritis - posing a diagnostic pitfall. This is clinically relevant because of the crucial difference in the therapeutic approach. The diagnosis of SAGN is further complicated by the variability in the degree of glomerular IgA (and C3) staining, the extent of electron dense immune-type deposits, and positive ANCA serology in some patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a thorough histopathologic review of our single-center cohort of 78 culture-proven SAGN biopsies to assess the spectrum of IgA staining, prevalence of ANCA serology, prevalence of subepithelial "humps," and other histologic features to distinguish from primary IgA nephropathy. RESULTS: Among the 78 SAGN biopsies, IgA staining was trace in 25%, mild in 19%, moderate in 44%, and strong in 12% of the cases. C3 was frequently moderate-to-strong but was trace in 14% of the biopsies. Concomitantly trace IgA, IgG, and C3 (pauci-immune pattern) was seen in 13%. Crescents were present in 35% of the SAGN biopsies. Out of 41 patients tested for ANCA, nine (22%) were positive, including patients with endocarditis and other infections. Subepithelial humps were identified in only 31% of the SAGN biopsies. CONCLUSIONS: SAGN biopsies show marked variability in IgA immunofluorescence staining and low frequency of subepithelial humps compared with poststreptococcal GN. Occasional ANCA positivity is present in cases of SAGN, even in infections other than endocarditis. Therefore, biopsy diagnosis can be difficult particularly when clinical symptoms of infection are subtle. Both the pathologist and the nephrologist should be aware of these diagnostic pitfalls.