Contribution of grade, vascular invasion and age to outcome in clinically localized renal cell carcinoma

Griffiths, David; Verghese, A; Golash, Anurag; Kynaston, Howard; Matthews, P. N.; Hart, A. J. L.; Court, Jacquelyn

doi:10.1046/j.1464-410x.2002.02661.x

Cited by 48 publications

(45 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, Lisanti and co-workers (Liu et al, 2002) have shown that, within an in vitro model of angiogenesis, the direct delivery of caveolin-1-derived peptides to the cytoplasm of endothelial cells is sufficient to induce capillary tubule formation. These findings are of significance since several independent studies advocate that the presentation of angiogenesis and microvascular invasion in patients who undergo surgery for RCC are at high risk for developing metastatic disease (Van Poppel et al, 1997;Dekel et al, 2002;Griffiths et al, 2002). More work will be required to determine whether or not caveolin-1 immunoreactivity is a useful clinical marker.…”

Section: Discussionmentioning

confidence: 92%

Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma

2003

View full text Add to dashboard Cite

Renal cell carcinomas, although usually apparently fully resected at surgery, commonly recur as distant metastasis. New markers are needed to predict which patients may relapse especially as novel methods of treatment (e.g. laproscopic resection) may make it impossible to assess conventional pathological prognostic markers. The caveolins are a family of proteins that represent the major structural components of caveolae; recent work suggests that these may have influence on several signalling pathways and they are thus potential prognostic markers. Immunohistochemistry for caveolin-1 was performed on sections of peripheral tumour from 114 consecutative nonmetastatic RCCs. Cytoplasmic caveolin-1 immunohistochemical (ICC) reaction was scored on a semiquantative scale of 1 -3. Immunohistochemical score was tested for impact on disease-free survival by Kaplan -Meier and Cox regression methods. A total of 50 tumours had ICC score 1; 43 had score 2 and 21 score 3. Larger, higher grade and tumours with vascular invasion had significantly higher scores. On univariate survival analysis (Kaplan -Meier), patients with tumours scoring 1 had a mean disease-free survival of 6.61 years (95% CI 5.76 -7.46) compared with 5.4 years (4.53 -6.30) and 3.15 years (1.87 -4.44) for scores 2 and 3, respectively. This is a significant difference (P ¼ 0.0017 log rank test). On multivariate analysis with size, grade and caveolin ICC score as independent covariates, caveolin ICC score 3 was an influential predictor of poor disease-free survival with a hazard ratio of 2.6 (P ¼ 0.03). We conclude that cytoplasmic overexpression of caveolin-1 predicts a poor prognosis in RCC; that this is likely to be a useful prognostic marker and that it may have importance in tumour progression.

show abstract

Section: Discussionmentioning

confidence: 92%

Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma

2003

View full text Add to dashboard Cite

show abstract

“…We have previously shown 31 the covariates of tumor grade, vascular invasion, and capsular invasion to be influential prognostic factors in RCC, but when tumor size and tumor type were not. Therefore, tumor grade, vascular invasion, and capsular invasion together with pERK were entered into the model.…”

Section: Cox Regression Multivariate Analysismentioning

confidence: 96%

Activated extracellular signal‐regulated kinase is an independent prognostic factor in clinically confined renal cell carcinoma

Campbell

Nuttall

Griffiths

et al. 2009

Cancer

View full text Add to dashboard Cite

BACKGROUND: Extracellular signal‐regulated kinase (ERK) promotes proliferation, metastasis, and poor survival in cancers of the breast, lung, and liver. Advanced localized renal cell carcinoma (RCC) is extraordinarily treatment resistant and has high recurrence rates despite surgery. Limited data exist regarding the prognostic significance of activated (phosphorylated) ERK in RCC. The authors hypothesized that activated ERK (pERK) promotes disease progression and metastasis in localized RCC and may be of value as a biomarker to predict disease recurrence. METHODS: The expression profile of pERK was examined by immunocytochemistry using a tissue microarray constructed from 174 drug treatment–naive patients who had undergone radical nephrectomy for localized RCC. Levels of tumor‐cell specific pERK were scored and correlated with clinicopathologic parameters of RCC and disease‐free survival. RESULTS: Immunostaining for pERK was present in 36% of all RCCs, with a predominance found in the clear cell histologic subtype. High expression was associated with increased tumor size, increased TNM stage, and vascular invasion. Patients with pERK‐positive tumors had a mean disease‐free survival of 4.19 years, compared with 6.38 years for patients with pERK‐negative tumors (P < .001). Cox regression models revealed pERK to be a significant independent predictor of disease‐free survival, with a hazards score of 2.9 (P < .001), a value similar to tumor grade (hazards ratio, 3.01; P < .001). CONCLUSIONS: Expression of pERK is an independent prognostic factor in RCC that is associated with advanced and aggressive pathologic features of renal tumors and predicts the onset of metastasis in patients with localized disease. Cancer 2009. © 2009 American Cancer Society.

show abstract

“…Although the specific mechanism by which caveolin-1 facilitates cancer progression is still unclear, the strong correlation with vascular invasion suggests that caveolin-1 contributes to angiogenesis and metastasis. Vascular invasion is considered to be one of the most important and robust pathological variables for RCC evaluation (Griffiths et al, 2002;Gonc¸alves et al, 2004;Dall'Oglio et al, 2007). Therefore, we constructed a multivariate Cox regression Hazard model to determine if coexpression of caveolin-1 and pAKT could be a superior prognosticator in a preoperative assessment scheme.…”

Section: Discussionmentioning

confidence: 99%

“…None of the patients had received treatment before surgery or had evidence of either lymph node or distant metastatic disease either before or at surgery. Histology reports and slides were available in all cases and reviewed by a pathologist without knowledge of the clinical outcome and assessed for histological type using the Heidelberg classification (Kovacs et al, 1997), Fuhrman nuclear grade (Fuhrman et al, 1982), the presence or absence of any vascular invasion (either microvascular invasion, renal vein invasion or inferior vena cava invasion) (Griffiths et al, 2002) and whether or not there was capsular penetration with cellular invasion of perinephric fat (Thomas et al, 2003).…”

Section: Patients and Rcc Tissue Microarraymentioning

confidence: 99%

“…Complete clinical follow-up was carried out as previously described (Griffiths et al, 2002;Campbell et al, 2003), and the following information extracted from the patients notes date of birth, sex, date of surgery, date last seen, date of death, cause of death and the date on which recurrent or metastatic disease was first identified.…”

Section: Patients and Rcc Tissue Microarraymentioning

confidence: 99%

See 1 more Smart Citation

Combined expression of caveolin-1 and an activated AKT/mTOR pathway predicts reduced disease-free survival in clinically confined renal cell carcinoma

et al. 2008

View full text Add to dashboard Cite

We previously reported that tumour-associated caveolin-1 is a potential biomarker in renal cell carcinoma (RCC), whose overexpression predicts metastasis following surgical resection for clinically confined disease. Much attention has recently focused on the AKT/mTOR pathway in a number of malignancies, including RCC. Since caveolin-1 and the AKT/mTOR signalling cascade are independently shown to be important regulators of tumour angiogenesis, we hypothesised that caveolin-1 interacts with the AKT/ mTOR pathway to drive disease progression and metastasis in RCC. The aims of this study were to determine (i) the expression status of the activated AKT/mTOR pathway components (phosphorylated forms) in RCC and (ii) their prognostic value when combined with caveolin-1. Immunohistochemistry for caveolin-1, pAKT, pmTOR, pS6 and p4E-BP1 was performed on tissue microarrays from 174 clinically confined RCCs. Significantly decreased mean disease-free survival was observed when caveolin-1 was coexpressed with either pAKT (2.95 vs 6.14 years), pmTOR (3.17 vs 6.28 years), pS6 (1.45 vs 6.62 years) or p4E-BP1 (2.07 vs 6.09 years) than when neither or any one single biomarker was expressed alone. On multivariate analysis, the covariate of 'caveolin-1/AKT' (neither alone were influential covariates) was a significant influential indicator of poor disease-free survival with a hazard ratio of 2.13 (95% CI: 1.15 -3.92), higher than that for vascular invasion. Tumours that coexpressed caveolin-1 and activated mTOR components were more likely to be larger, higher grade and to show vascular invasion. Our results provide the first clinical evidence that caveolin-1 cooperates with an activated AKT/mTOR pathway in cancer and may play an important role in disease progression. We conclude that evaluation of the 'caveolin-1/AKT/mTOR axis' in primary kidney tumours will identify subsets of RCC patients who require greater postoperative surveillance and more intensive treatment.

show abstract

Contribution of grade, vascular invasion and age to outcome in clinically localized renal cell carcinoma

Abstract: Objective To determine the relative prognostic importance of microvascular invasion in apparently localized renal cell carcinoma (RCC

Cited by 48 publications

References 11 publications

Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma

Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma

Activated extracellular signal‐regulated kinase is an independent prognostic factor in clinically confined renal cell carcinoma

Combined expression of caveolin-1 and an activated AKT/mTOR pathway predicts reduced disease-free survival in clinically confined renal cell carcinoma

Contact Info

Product

Resources

About