Re: Kidney Size and Cancer-Specific Survival for Patients Undergoing Nephrectomy for pT1 Clear Cell Renal Cell Carcinoma

414 Background: While mutations in PBRM1 (~40%) and BAP1(~10%) are associated with clinical outcomes and pathologic features in clear cell renal cell carcinoma (ccRCC), the impact of protein expression of these genes remains unknown. Herein, we quantify PBRM1/BAP1 protein expression in a large cohort of patients with localized ccRCC and associate expression with cancer-specific survival (CSS) and pathologic features. Methods: We utilized the Mayo Clinic Renal Registry and identified 1,416 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/3/1990 and 4/14/2009. We used immunohistochemistry (IHC) to detect PBRM1/BAP1 expression, and a central pathologist blinded to the outcomes scored tumors as either positive or negative. Tumors with heterogeneous or equivocal staining were excluded from this analysis. We generated Cox proportional hazard regression models for associations with ccRCC-SS, and we employed Mann-Whitney U tests for associations with pathologic features. Results: Of the 1,416 samples, 1,232 (87%) were PBRM1/BAP1 positive or negative, 163 (11%) had heterogeneous staining, and 21 (1%) could not be assessed. The distribution and association of PBRM1/BAP1 phenotypes with clinical outcomes are listed in the table below. PBRM1+/BAP1+ tumors have the best CSS, and PBRM1-/BAP1- have the worst. In addition, PBRM1/BAP1 expression strongly associated with the tumor size, stage, grade, and tumor necrosis (p<0.0001). Conclusions: This study is the first and largest to quantify PRBM1/BAP1 protein expression in ccRCC tumors. We were able to quantify PBRM1/BAP1 through IHC in the vast majority of tumors (87%), and PRBM1/BAP1 expression strongly associates with both CSS and pathologic tumor characteristics. Our data confirms our previous findings of the importance of PRBM1/BAP1 in the molecular pathogenesis of ccRCC. [Table: see text]

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1252 THREE DIMENSIONAL TUMOR VOLUME AND CANCER-SPECIFIC SURVIVAL FOR PATIENTS UNDERGOING NEPHRECTOMY TO TREAT PT1 CLEAR CELL RENAL CELL CARCINOMA

The Journal of Urology ◽

10.1016/j.juro.2011.02.937 ◽

2011 ◽

Vol 185 (4S) ◽

Author(s):

Alexander Parker ◽

David Thiel ◽

Christine Lohse ◽

Michelle Arnold ◽

Jacob Jorns ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Tumor Volume ◽

Clear Cell ◽

Three Dimensional ◽

Cell Renal Cell Carcinoma ◽

Cancer Specific Survival

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The impact of three-dimensional tumor volume on cancer-specific survival for patients with pT1 clear-cell renal cell carcinoma

World Journal of Urology ◽

10.1007/s00345-015-1592-6 ◽

2015 ◽

Vol 34 (1) ◽

pp. 83-88 ◽

Cited By ~ 3

Author(s):

Wan Song ◽

Byong Chang Jeong ◽

Seong Il Seo ◽

Seong Soo Jeon ◽

Hyun Moo Lee ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Tumor Volume ◽

Clear Cell ◽

Three Dimensional ◽

Cell Renal Cell Carcinoma ◽

Cancer Specific Survival ◽

The Impact

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Association of topoisomerase II expression and cancer-specific death in patients with surgically resected clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.446 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 446-446 ◽

Cited By ~ 1

Author(s):

Faithlore Patrice Gardner ◽

Richard Wayne Joseph ◽

Daniel Serie ◽

Tracy W. Hilton ◽

Mansi Parasramka ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Cancer Specific Survival ◽

Risk Of Death ◽

Pathologic Features ◽

Increased Risk ◽

Risk Of Cancer

446 Background: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death. Methods: We identified 947 patients who underwent nephrectomy to treat clinically localized ccRCC between January 16, 1990, and September 27, 2006. TOP2a expression was assessed using IHC and scored as number of positive cells per mm2. We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features, we employed Kruskal-Wallis tests and for associations with cancer-specific survival, we generated Cox proportional hazard regression models. Results: HigherTOP2a expression is associated with later stage, higher grade and higher Mayo SSIGN score (all p < 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend < 0.0001). Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.31 95% CI 1.64-3.25; p < 0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ~95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.09 95% CI 1.29-7.40; p = 0.01). Conclusions: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients.

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An optimized microRNA signature algorithm to predict clear cell renal cell carcinoma metastasis: A 265-case validation study using paraffin specimens.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.612 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 612-612

Author(s):

Huiqing Wu ◽

Xiwei Wu ◽

Jennifer M Jin ◽

Arthur X Li ◽

Tommy Tong ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Multivariate Logistic Regression Analysis ◽

Cell Renal Cell Carcinoma ◽

Cancer Specific Survival ◽

Predictive Values ◽

Training Cohort ◽

Dismal Prognosis

612 Background: Clear cell renal cell carcinoma (ccRCC) metastasis is associated with a dismal prognosis. Early identification of patients at high or low risk of metastasis may help to guide appropriate treatment. There are currently no reliable clinico-pathologic and laboratory modalities for this purpose in a routine clinical setting. We previously performed a microarray study using frozen ccRCC specimens and identified dysregulation of 4 microRNAs (miRNAs), miR-10b, miR-139-5p, miR-130b and miR-199b-5p, to be highly associated ccRCC metastasis and prognosis. Methods: We established a training cohort including formalin-fixed paraffin-embedded (FFPE) specimens of localized (n = 13; pT1) and metastatic (n = 15; M1) ccRCCs. We measured the expression of the 4 miRNAs of the training cohort samples by quantitative RT-PCR, normalized with miR-24, one of the most stably expressed miRNAs in human renal tissue as we previously reported. Using the risk score method, we rebuilt a mathematical formula with cutoff points to predict a patient to be at high, low or equivocal risk of metastasis. We validated the signature in an FFPE test cohort of 265-case primary ccRCCs. We examined the signature performance and its correlation with the cancer-specific survival. Results: Multivariate logistic regression analysis showed the signature to be highly associated with ccRCC metastasis (OR 7.67, 95%Cl 2.80-21.09, p < 0.0001), with the overall sensitivity and specificity of 80% and 76%. The sensitivities and specificities were 72% and 78%, 70% and 67%, and 78% and 75% for stage I, II or III patients, respectively. The signature predicted metastasis of small ccRCCs ( ≤ 4.0 cm), with the sensitivity of 60% and specificity of 77%. The overall positive and negative predictive values (PPV and NPV) were 61% and 89%. The area under the curve of ROC was 0.8. The signature was also found to be well correlated with worse cancer-specific survival (HR 3.06, 95%Cl 1.49-6.93, p < 0.01). Conclusions: This optimized miRNA signature can reliably predict ccRCC metastasis and prognosis and may help to stratify patients for more appropriate therapies and suitable clinical trials.

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