All solid tumours require a vascular supply in order to progress. Although the ability to induce angiogenesis (new blood vessel growth) has long been regarded as essential to this purpose, thus far, anti-angiogenic therapies have shown only modest efficacy in patients. Importantly, overshadowed by the literature on tumour angiogenesis is a long-standing, but continually emerging, body of research indicating that tumours can grow instead by hijacking pre-existing blood vessels of the surrounding nonmalignant tissue. This process, termed vessel co-option, is a frequently overlooked mechanism of tumour vascularization that can influence disease progression, metastasis and response to treatment. In this Review, we describe the evidence that tumours located at numerous anatomical sites can exploit vessel co-option. We also discuss the proposed molecular mechanisms involved and the multifaceted implications of vessel co-option for patient outcomes. Despite much hope, anti-angiogenic agents have largely failed to achieve the promise demonstrated in preclinical models. In this Review, the authors discuss an alternative hypothesis — vessel co-option — that might explain many of these failures and describe the evidence for a role of this largely overlooked aspect of tumour biology.

Vessel co-option in cancer.

Purpose
To investigate associations between imaging features and mutational status of clear cell renal cell carcinoma (ccRCC).

/pdf/radiogenomics-of-clear-cell-renal-cell-carcinoma-preliminary-mcrv8qnk51.pdf

Radiogenomics of clear cell renal cell carcinoma: preliminary findings of The Cancer Genome Atlas–Renal Cell Carcinoma (TCGA–RCC) Imaging Research Group

Tumor necrosis (TN) correlates with adverse outcomes in numerous solid tumors. However, its prognostic value in renal cell carcinoma (RCC) remains unclear. In this study, we performed a meta-analysis to evaluate associations between TN and cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS) and progression-free-survival (PFS) in RCC. Electronic searches in PubMed, EMBASE and Web of Science were conducted according to the PRISMA statement. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate relationships between TN and RCC. A fixed- or random-effects model was used to calculate pooled HRs and 95%CIs according to heterogeneity. A total of 34 cohort studies met the eligibility criteria of this meta-analysis. The results showed that TN was significantly predictive of poorer CSS (HR = 1.37, 95% CI: 1.23–1.53, p < 0.001), OS (HR = 1.29, 95% CI: 1.20–1.40, p < 0.001), RFS (HR = 1.55, 95% CI: 1.39–1.72, p < 0.001) and PFS (HR = 1.31, 95% CI: 1.17–1.46, p < 0.001) in patients with RCC. All the findings were robust when stratified by geographical region, pathological type, staging system, number of patients, and median follow-up. The present study suggests that TN is associated with CSS, OS, RFS and PFS clinical outcomes of RCC patients and may serve as a predictor of poor prognosis in these patients.

/pdf/tumor-necrosis-as-a-prognostic-variable-for-the-clinical-1rmx53uizg.pdf

Tumor necrosis as a prognostic variable for the clinical outcome in patients with renal cell carcinoma: a systematic review and meta-analysis

We developed and validated an architecture-based grading for clear cell renal cell carcinoma (ccRCC) in an observational retrospective cohort study including 506 tumors (principal cohort, n=254; validation cohort, n=252). Study endpoints were disease-free survival (DFS) and cancer-specific survival (CSS). Relationships with outcome were analyzed using Harrell concordance index, time-dependent receiver operating characteristic curve, area under curve, and Cox regression model. An architecture-based grading was devised on positive likelihood ratio (LR+) for DFS at 50 months as follows: grade 1 (LR+<0.8), cystic, compact, acinar, clear cell papillary RCC-like, and/or regressive patterns; grade 2 (1.2≤LR+<5), large nest, alveolar, papillary, chromophobe/oncocytic cell-like, eosinophilic hyaline globule, and/or intratumoral inflammatory reaction patterns; grade 3 (5≤LR+<10), rhabdoid, tumor giant cell, enlarged vascular space, and/or hereditary leiomyomatosis renal cell carcinoma (HLRCC)-like patterns; grade 4 (LR+≥10), sarcomatoid, infiltrative growth patterns, and lymphatic invasion. In the principal cohort, 3-tier (grades 1-2, 3, and 4) and 4-tier architectural scores outperformed World Health Organization/International Society of Urological Pathology, and World Health Organization/ International Society of Urological Pathology+necrosis gradings for DFS and CSS, and constituted an independent predictor for DFS (hazard ratio [HR]=5.91; P<6.7E-10) and CSS (HR=4.49; P=2.2E-03), retained in the localized (pT1-3N0M0) ccRCC subgroup (HR=6.10; P=1.3E-07 for DFS, and HR=20.09; P=9.4E-05 for CSS). On comparing with integrated staging systems, architectural grade with 1 morphologic datum remained an independent predictor of CSS, as did University of California Los Angeles Integrated Staging System and SSIGN, and was associated with the highest HR (HR=2.60; P=9.1E-04 in all patients; HR=4.38; P=2.0E-05 in the localized ccRCC subgroup). Architecture-based score for ccRCC outperforms all other morphologic grading systems and constitutes an independent predictor for DFS and CSS. As the predictive values of 3-tier and 4-tier architecture-based scores were similar throughout the study, we proposed to keep the simplified version as the final score, and to define 3 risk groups as follows: low risk (grades 1 to 2), intermediate risk (grade 3), and high risk (grade 4).

Architectural Patterns are a Relevant Morphologic Grading System for Clear Cell Renal Cell Carcinoma Prognosis Assessment: Comparisons With WHO/ISUP Grade and Integrated Staging Systems.

Infiltrative Renal Masses: Clinical Significance and Fidelity of Documentation

Objectives: To assess the validity of growth pattern as a unique prognostic parameter for clear cell renal cell carcinoma (ccRCC). Methods: In total, 561 patients with pathologic tumor stage 1 (pT1), pT2, and pT3a ccRCC without preoperative metastasis were evaluated. Clinicopathologic parameters, including pathologic tumor stage, Fuhrman grade, tumor necrosis, lymphovascular invasion, and growth pattern, were analyzed to predict disease-free survival (DFS) and cancer-specific survival (CSS). Results: Growth patterns were defined as follows: expansive included tumors with well-circumscribed margins without normal renal tissue in the tumor, and infiltrative involved tumors with ill-circumscribed margins or normal renal tissue in the tumors. In multivariate analysis, Fuhrman grade, tumor necrosis, and growth pattern were useful predictors of DFS, whereas Fuhrman grade and growth pattern were useful predictors of CSS, although only 30 cases showed the infiltrative pattern. Conclusions: Growth pattern can be considered a new prognostic parameter for ccRCC.

/pdf/growth-pattern-an-important-pathologic-prognostic-parameter-1dzrj0ygrg.pdf

Growth pattern, an important pathologic prognostic parameter for clear cell renal cell carcinoma.

Sassa N, Tsuzuki T, Fukatsu A, Majima T, Kimura T, Nishikimi T, Yoshino Y, Hattori R & Gotoh M (2012) Histopathology61, 620–628



Is pT3 urothelial carcinoma of the renal pelvis a homogeneous disease entity? Proposal for a new subcategory of the pT3 classification



Aims:  The prognosis of urothelial carcinoma of the renal pelvis (UCRP) is heterogeneous, especially in pT3 patients. The degree of tumour parenchymal invasion is not considered for pathological tumour (pT) staging. The aim of this study was to investigate whether quantitative assessment of invasion provides a better estimation of prognosis for UCRP in pT3 patients.



Methods and results:  We reclassified pT3 cases into two subcategories: pT3a, in which UCRP extended only into the renal medulla; and pT3b, in which UCRP extended into the renal cortex and/or in which UCRP exhibited peripelvic fat invasion. We examined our proposed pT classification and other pathological parameters, including necrosis, lymph–vascular invasion (LVI), 1973 World Health Organization (WHO) grading, WHO/International Society of Urological Pathology grading, adjuvant chemotherapy, and pathological lymph node metastasis (pN). The study included 275 patients. Among 96 patients with pT3, there was a statistically significant difference between the pT3a and pT3b subcategories in cancer-specific survival (P < 0.001). Our proposed pT classification, as well as necrosis, LVI, 1973 WHO grading, and pN, demonstrated prognostic differences in univariate analysis, whereas in multivariate analysis, only our proposed classification (P = 0.008) and pN (P = 0.002) were statistically significant.



Conclusions:  The pT3b subcategories should be regarded as true pT3, having the established features of that stage, whereas pT3a has a better prognosis.

Is pT3 urothelial carcinoma of the renal pelvis a homogeneous disease entity? Proposal for a new subcategory of the pT3 classification.

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Growth pattern, an important pathologic prognostic parameter for clear cell renal cell carcinoma.

Is pT3 urothelial carcinoma of the renal pelvis a homogeneous disease entity? Proposal for a new subcategory of the pT3 classification.