Vascularity of primary and metastatic renal cell carcinoma specimens

Aziz, Saadia A.; Sznol, Joshua; Adeniran, Adebowale; Colberg, John W.; Camp, Robert L.; Kluger, Harriet M.

doi:10.1186/1479-5876-11-15

Cited by 34 publications

(32 citation statements)

References 44 publications

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“…At a b value of 500 s/mm 2 , the influence of the perfusion fraction on ADC values is relatively low but not totally eliminated. Therefore, it could be hypothesized that strongly increased blood perfusion and intratumoral angiogenesis, as found in clear cell RCC [32], could contribute to the high ADC values in clear cell RCC. This hypothesis is supported by the results of preliminary studies [22, 33] that used intravoxel incoherent motion imaging to assess tumor perfusion and also reported higher values for perfusion parameters in clear cell RCC.…”

Section: Discussionmentioning

confidence: 99%

Use of DWI in the Differentiation of Renal Cortical Tumors

Hötker

Mazaheri

Wibmer

et al. 2016

American Journal of Roentgenology

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OBJECTIVE The purpose of this study was to differentiate clear cell renal cell carcinoma (RCC) from other common renal cortical tumors by use of DWI. MATERIALS AND METHODS The study included 117 patients (mean age, 60 years) with 122 histopathologically confirmed renal cortical tumors who underwent 1.5-T MRI that included DWI before they underwent nephrectomy between 2006 and 2013. For each tumor, two radiologists independently evaluated apparent diffusion coefficient (ADC) values on the basis of a single ROI in a nonnecrotic area of the tumor and also by assessment of the whole tumor. The concordance correlation coefficient (CCC) was calculated to assess interreader agreement. The mean ADC values of clear cell RCC and every other tumor subtype were compared using an exact Wilcoxon rank sum test. RESULTS Interreader agreement was excellent and higher in whole-tumor assessment (CCC, 0.982) than in single-ROI analysis (CCC, 0.756). For both readers, ADC values for clear cell RCC found on single-ROI assessment (2.19 and 2.08 × 10−3 mm2/s) and whole-tumor assessment (2.30 and 2.32 × 10−3 mm2/s) were statistically significantly higher than those for chromophobe, papillary, or unclassified RCC (p < 0.05) but were similar to those for oncocytoma found on single-ROI assessment (2.14 and 2.32 × 10−3 mm2/s) and whole-tumor assessment (2.38 and 2.24 × 10−3 mm2/s). ADC values were also higher for clear cell RCC than for angiomyolipoma, but the difference was statistically significant only in whole-tumor assessment (p < 0.03). CONCLUSION ADC values were statistically significantly higher for clear cell RCC than for chromophobe, papillary, or unclassified RCC subtypes; however, differentiating clear cell RCC from oncocytoma by use of DWI remains especially challenging, because similar ADC values have been shown for these two tumor types.

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Section: Discussionmentioning

confidence: 99%

Use of DWI in the Differentiation of Renal Cortical Tumors

Hötker

Mazaheri

Wibmer

et al. 2016

American Journal of Roentgenology

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“…Each tumor site was represented by four cores from different areas of the specimen; two cores from each tumor site were included in each of two TMA blocks (8 cores of each patient in total). Specimen accrual, tumor characteristics (including size, grade, histology and site of metastases), and other clinical information have been described 22, 23. Briefly, this cohort included 20 males (60%) and 14 females (40%).…”

Section: Methodsmentioning

confidence: 99%

“…The majority of metastatic specimens were lung metastases but also included several other visceral sites, skin, soft tissue and soft tissue components of bone metastases. Both TMA blocks contained identical cell lines, cored from cell pellets, as previously detailed for normalization between TMA blocks 22, 23. To verify antibody specificity, we used small TMAs containing placental and tonsil tissue (known to be positive for PD-L1 expression) and pellets from MEL-624 cell lines, overexpressing or not overexpressing PD-L1, as previously described 14…”

Section: Methodsmentioning

confidence: 99%

PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases

Jilaveanu¹,

Shuch²,

Zito³

et al. 2014

J. Cancer

145

107

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Background: Expression of programmed death ligand (PD-L1/B7-H1/CD274) represents a mechanism of immune escape for renal cell carcinoma (RCC) cells. Drugs blocking PD-L1 or its receptor are in clinical development and early data suggests that tumor PD-L1 expression may predict response.Patients and Methods: A tissue microarray (TMA) consisting of four biopsy cores from 34 matched pairs of nephrectomy and metastatic sites of clear cell RCC was used to assess PD-L1 expression by quantitative immunofluorescence. Assessment of intra- and inter-tumor heterogeneity and primary and metastatic tumor expression was performed using a method of Automated Quantitative Analysis (AQUA).Results: The median AQUA scores were higher in metastatic than primary specimens (P < 0.0001). The correlation between PD-L1 expression in matched primary and metastatic specimens was weak (R= 0.24). Within a given tumor, variable PD-L1 staining heterogeneity was seen, however the degree of heterogeneity was similar in primary and metastatic sites (P = 0.482).Conclusions: The weak correlation between PD-L1 expression in primary and metastatic sites for a given patient suggests that expression in nephrectomy specimens cannot be used to select metastatic RCC patients for PD-L1 and PD-1 inhibitors. The intra-tumor heterogeneity seen in both primary and metastatic specimens indicates that a single core biopsy might not be sufficient to determine PD-L1 expression.

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“…Two separate tissue microarray (TMA) sets were constructed using archival, surgical material from non-overlapping resected RCC cases that have been described previously 25 26. Cohort A consisted of a large series of patients (n=334) with renal tumours resected between 1987 and 1999 and included a total of two 0.6 mm cores from the tumour.…”

Section: Methodsmentioning

confidence: 99%

“…The array set included eight 0.6 mm cores, four from both the primary renal tumour and four from matched metastatic sites, two on each slide 25. Clinical data was available for 34 patients.…”

Section: Methodsmentioning

confidence: 99%

PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma?

et al. 2014

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Aims Immunohistochemical stains have greatly improved the diagnostic accuracy of renal cell carcinoma (RCC) for primary and distant tumours. We evaluate a marker that has recently been incorporated in clinical practice, PAX-8, in primary and metastatic RCCs. Methods Two distinct tissue microarrays were used, one consisting of over 334 renal tumours, 294 with adjacent normal kidney and the other with 40 matched nephrectomy and metastatic sites of RCC. PAX-8 expression was assessed by a method of quantitative immunofluorescence. Results PAX-8 was positive in 96% (146/152) of normal renal tissue and 83% (227/272) of renal tumours. PAX-8 staining was positive in clear cell, papillary and chromophobe tumours in 80% (165/207), 95% (39/41) and 100% (6/6) of samples, respectively. Overall, intensity of PAX-8 expression was significantly higher in RCC metastatic sites than in the primary site (p=0.0047), however, in matched sites there was no statistically significant difference in the proportion of positive versus negative specimens (p=0.274). Conclusions As the role of molecular markers expands in the diagnostic algorithm, this study confirms that PAX-8 expression is a useful diagnostic marker for RCC. PAX-8 expression was found in the primary tumour and distant sites. Compared with normal tissue and other histological types, clear cell RCC has lower PAX-8 expression and is less frequently positive, therefore, the lack of expression does not exclude a tumour of renal origin.

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Vascularity of primary and metastatic renal cell carcinoma specimens

Cited by 34 publications

References 44 publications

Use of DWI in the Differentiation of Renal Cortical Tumors

Use of DWI in the Differentiation of Renal Cortical Tumors

PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases

PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma?

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