Positive surgical margin following radical nephrectomy is an independent predictor of local recurrence and disease-specific survival.

BACKGROUND: Positive surgical margins (PSM) are recognized as an adverse prognostic sign and are often associated with higher rates of local and systemic disease recurrence. The data regarding the oncological outcome for PSM following radical nephrectomy (RN) is limited. We examined the predictive factors for PSM and its influence on survival and site of recurrence in patients treated with RN for renal cell carcinoma (RCC). METHODS: Clinical, pathologic and follow-up data on 714 patients undergoing RN for kidney cancer were analyzed. Secondary analysis included 44 patients with metastatic RCC upon diagnosis who underwent cytoreductive nephrectomy (CRN). Univariate and multivariable logistic regression models were fit to determine clinicopathologic features associated with PSM. A Cox proportional-hazards regression model was used to test the independent effects of clinical and pathologic variables on survival. RESULTS: PSM was documented in 17 cases (2.4%). PSM were associated with tumour size, advanced pathologic stage (pT3 vs. ≤ pT2) and presence of necrosis. On multivariate analysis, cancer-specific survival (CSS) was associated with tumour stage, size, presence of necrosis and PSM. PSM was also associated with local recurrence but not distant metastasis or overall survival (OS). CSS and OS were comparable between the PSM and metastatic RCC groups, but significantly lower than the negative margin group. CONCLUSIONS: The prevalence of PSM following RN is rare. Pathological data, including advanced stage (> pT2), tumour necrosis and tumour size, are associated with the presence of PSM. PSM is associated with tumour recurrence and CSS. Patients with PSM are a potential group for adjuvant therapy or for more careful and thorough follow-up following surgery.

Multiple imprinted and stemness genes provide a link between normal and tumor progenitor cells of the developing human kidney.

Wilms' tumor (WT), the embryonic kidney malignancy, is suggested to evolve from a progenitor cell population of uninduced metanephric blastema, which typically gives rise to nephrons. However, apart from blastema, WT specimens frequently contain cells that have differentiated into renal tubular or stromal phenotypes, complicating their analysis. We aimed to define tumor-progenitor genes that function in normal kidney development using WT xenografts (WISH-WT), in which the blastema accumulates with serial passages at the expense of differentiated cells. Herein, we did transcriptional profiling using oligonucleotide microarrays of WISH-WT, WT source, human fetal and adult kidneys, and primary and metastatic renal cell carcinoma. Among the most significantly up-regulated genes in WISH-WT, we identified a surprising number of paternally expressed genes (PEG1/MEST, PEG3, PEG5/NNAT, PEG10, IGF2, and DLK1), as well as Meis homeobox genes [myeloid ecotropic viral integration site 1 homologue 1 (MEIS1) and MEIS2], which suppress cell differentiation and maintain self-renewal. A comparison between independent WISH-WT and WT samples by real-time PCR showed most of these genes to be highly overexpressed in the xenografts. Concomitantly, they were significantly induced in human fetal kidneys, strictly developmentally regulated throughout mouse nephrogenesis and overexpressed in the normal rat metanephric blastema. Furthermore, in vitro differentiation of the uninduced blastema leads to rapid down-regulation of PEG3, DLK1, and MEIS1. Interestingly, ischemic/reperfusion injury to adult mouse kidneys reinduced the expression of PEG3, PEG10, DLK1, and MEIS1, hence simulating embryogenesis. Thus, multiple imprinted and stemness genes that function to expand the renal progenitor cell population may lead to evolution and maintenance of WT.

Analysis of the prognostic impact of nestin expression in non-small cell lung cancer.

BACKGROUND: Nestin is an intermediary filament protein, expressed in progenitor cells of neural and muscle origin and in activated endothelium. The expression of this protein in tumours can be associated with degree of differentiation, biological potential and/or neoangiogenesis. AIMS: The aim of this study was to examine the immunohistochemical expression of nestin in primary non-small cell lung carcinomas (NSCLC) and to determine its prognostic significance. METHODS: Immunohistochemical detection of nestin was carried out on tissue microarrays constructed from 114 formalin-fixed and paraffin-embedded NSCLC samples. These included 78 squamous cell carcinomas and 37 adenocarcinomas. Expression of nestin was also analysed in 35 primary tumour independent NSCLC brain metastasis. The H-score and degree of nestin positive microvascularisation were determined. Both parameters correlated with the clinicopathological characteristics including disease-free and overall survival. Results. We demonstrated that expression of nestin is not significantly higher in tumour cells of adenocarcinomas than in sqamous cell carcinomas despite the fact that adenocarcinomas were more frequently positive (P≤0.30). On the other hand, nestin positivity and nestin positive neovascularisation were significantly more often found in stage IIIa tumours than tumours in stages I and II (P≤0.04, P≤0.02). Nestin expression was also significantly higher in brain metastases of squamous cell carcinomas than brain metastases of adenocarcinomas (P≤0.003). The expression of nestin, in general, did not significantly correspond to disease-free or overall survival. CONCLUSION: Nestin expression in NSCLCs is associated with poorer prognosis and with greater nestin-positive microvessel density.