Tumor Necrosis as Prognostic Indicator in Transitional Cell Carcinoma of the Upper Urinary Tract

Langner, Cord; Hutterer, Georg C.; Chromecki, Thomas; Leibl, Sebastian; Rehak, Peter; Zigeuner, Richard

doi:10.1016/j.juro.2006.04.019

Cited by 78 publications

(66 citation statements)

References 17 publications

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“…Therefore, the extent of necrosis is considered to represent the level of tumor hypoxia, and greater hypoxia is related to metastasis and poor prognosis. 24,25 In addition, tumor necrosis could result in release of a large number of proinflammatory cytokines, which stimulate tumor growth, and therefore correlate with a poor prognosis. 26,27 Tumor necrosis has been reported to have prognostic value in many solid caner types, such as colon, lung, 25 breast, 28 and renal malignancies, including both renal cell carcinoma 29,30 and upper urinary tract urothelial carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma

et al. 2017

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Early recurrence is common after curative hepatectomy for hepatocellular carcinoma and is associated with poor prognosis. This study aimed to identify risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma. Overall, 63 patients who underwent curative hepatectomy for hepatocellular carcinoma were enrolled. Patients were divided into the early recurrence group, who developed recurrence within 12 months after hepatectomy (n = 10), and the non-early recurrence group (n = 53). Clinicopathological factors of early recurrence were retrospectively analyzed. Among the 63 patients, 10 (15.9%) patients experienced early recurrence. Univariate analysis showed tumor necrosis (p = 0.012), level of PIVKA-II (prothrombin induced by vitamin K absence or antagonist-II; p = 0.002), and microvascular invasion (p = 0.029) to be associated with early recurrence. By multivariate analysis, there were significant differences in high PIVKA-II (p < 0.001) and tumor necrosis (p = 0.012) in patients with early recurrence. The optimal cutoff values of PIVKA-II and tumor necrosis were 46 mAU/mL and 3% of total tumor volume, respectively. Patients with a high preoperative PIVKA-II level and extent of tumor necrosis, which are independent risk factors for early recurrence, should be actively treated and monitored closely after hepatectomy.

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Section: Discussionmentioning

confidence: 99%

Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma

et al. 2017

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“…Necrosis is characterized by the disruption of cellular membranes and the release of cellular components including HMGB1 which promotes cancer cell growth, invasion, and progression (14)(15)(16)(17)(18). Tumour necrosis has been shown to indicate a poor prognosis (19,20) and to contribute to acquisition of chemoresistance in solid tumours, including breast cancer, non-small cell lung cancer, and gastroinstinal stromal tumours (21). However, the mechanism underlying necrosis-mediated chemoresistance remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Implication of necrosis-linked p53 aggregation in acquired apoptotic resistance to 5-FU in MCF-7 multicellular tumour spheroids

Kang¹

2010

Oncol Rep

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Abstract. Three-dimensional (3D) multicellular tumour spheroids (MTS) have been used as an in vitro model of solid tumours for drug resistance studies because they mimic the growth characteristics of in vivo tumours more closely than in vitro two-dimensional (2D) culture of cancer cell lines. As observed in solid tumours, MTS exhibits a proliferation gradient with outer regions consisting of proliferating cells that surround inner quiescent cells. The innermost cells in core regions undergo cell death mostly by necrosis to form necrotic core due to insufficient supply of oxygen and nutrient such as glucose with increasing size of spheroids. Tumour necrosis is thought to indicate a poor prognosis and to contribute to acquisition of chemoresistance in solid tumours; however, the mechanism underlying necrosis-mediated chemoresistance remains unclear. In this study, we examined the chemoresistance to 5-Fluorouracil (5-FU) using MCF-7 breast cancer MTS. 5-FU (400 μM) induced apoptosis in MCF-7 cell monolayer as determined by HO/PI staining, PARP cleavage, p53 induction, Bax induction, and Bcl-2 downregulation. When MCF-7 breast tumour spheroids were cultured on agarose for 8 days, they reached ~700 μm in diameter, with a necrotic core. We found that 5-FU-induced apoptosis is markedly reduced in spheroids that were cultured for 9 days and had necrotic core, compared with MCF-7 monolayer cells and spheroids that were cultured for 6 days and had no necrotic core, indicating that the formation of necrotic core may be linked to acquisition of chemoresistance to 5-FU. We also found that a specific set of cellular proteins including p53 was aggregated into a RIPAinsoluble form during MTS culture. Furthermore, most of p53 induced by 5-FU was aggregated in MTS with necrotic core. Our results suggest that necrosis-linked p53 aggregation may contribute to acquired apoptotic resistance to 5-FU in MTS model system.

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“…Whereas tumor stage and histologic grade are well established prognostic factors of outcome after RNU, the oncologic significance of other potentially relevant variables, such as tumor site, architecture, histologic tumor necrosis, lymphovascular invasion (LVI), and the presence of concomitant carcinoma-in situ (CIS), among others, has not been clearly established. 4,[8][9][10][11][12][13][14][15] Recognizing these limitations, we developed a comprehensive database incorporating the clinical and pathologic characteristics and outcomes of over 1300 patients treated with RNU for UTUC at 12 academic centers. Using this large international patient cohort, strict accrual criteria, and pathologic re-review of all slides, we sought to more clearly define the natural history, patterns of failure, and the impact of potential prognostic factors on relapse and survival after surgical management of UTUC.…”

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confidence: 99%

Outcomes of radical nephroureterectomy: A series from the Upper Tract Urothelial Carcinoma Collaboration

Margulis

Shariat²,

Matin

et al. 2009

Cancer

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Tumor Necrosis as Prognostic Indicator in Transitional Cell Carcinoma of the Upper Urinary Tract

Cited by 78 publications

References 17 publications

Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma

Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma

Implication of necrosis-linked p53 aggregation in acquired apoptotic resistance to 5-FU in MCF-7 multicellular tumour spheroids

Outcomes of radical nephroureterectomy: A series from the Upper Tract Urothelial Carcinoma Collaboration

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