Membranoproliferative glomerulonephritis in the setting of multicentric angiofollicular lymph node hyperplasia (Castleman's disease) complicated by Evan's syndrome.

Systemic Castleman's disease is a lymphoproliferative disorder with various clinical presentations and incompletely understood aetiology. The authors report on a rare case of the plasma cell variant of Castleman's disease associated with autoimmune haemolytic anaemia and autoimmune thrombocytopenia (Evan's syndrome) and complicated by mixed nephrotic-nephritic syndrome and acute renal failure due to an underlying glomerulopathy with microscopic and immunofluorescence findings suggestive of membranoproliferative glomerulonephritis (MPGN) type I. Immunocomplexed glomerulonephritis is rare in Castleman's disease, while, to the best of our knowledge, constellation of all these autoimmune phenomena is reported for the first time suggesting that apart from the putative role of VEGF and IL-6 in the pathogenesis of the disease, a more generalised immunological disturbance occurs, probably through autoantibodies induced by active polyclonal B cells raised from Castleman's disease tumour.

Replication protein A is an independent prognostic indicator with potential therapeutic implications in colon cancer.

Replication protein A (RPA), a component of the origin recognition complex, is required for stabilization of single-stranded DNA at early and later stages of DNA replication being thus critical for eukaryotic DNA replication. Experimental studies in colon cancer cell lines have shown that RPA protein may be the target of cytotoxins designed to inhibit cellular proliferation. This is the first study to investigate the expression of RPA1 and RPA2 subunits of RPA protein and assess their prognostic value in colon cancer patients. We analyzed immunohistochemically the expression of RPA1 and RPA2 proteins in a series of 130 colon cancer resection specimens in relation to conventional clinicopathological parameters and patients' survival. Statistical significant positive associations emerged between: (a) RPA1 and RPA2 protein expressions (P=0.0001), (b) RPA1 and RPA2 labelling indices (LIs) and advanced stage of the disease (P=0.001 and 0.003, respectively), (c) RPA1 and RPA2 LIs and the presence of lymph node metastasis (P=0.002 and 0.004, respectively), (d) RPA1 LI and the number of infiltrated lymph nodes (P=0.021), (e) RPA2 LI and histological grade of carcinomas (P=0.05). Moreover, a statistical significant higher RPA1 LI was observed in the metastatic sites compared to the original ones (P=0.012). RPA1 and RPA2 protein expression associated with adverse patients' outcome in both univariate (log rank test: P<0.00001 and 0.00001, respectively) and multivariate (Cox model: P=0.092 and 0.0001, respectively) statistical analysis. Statistical significant differences according to the expression of RPA1 and RPA2 proteins were also noticed in the survival of stage II (P<0.00001 and 0.0016, respectively) and stage III (P=0.0029 and 0.0079, respectively) patients. In conclusion, RPA1 and RPA2 proteins appear to be useful prognostic indicators in colon cancer patients and attractive therapeutic targets for regulation by tumor suppressors or other proteins involved in the control of cell proliferation.