Evaluation of tumor-associated macrophages as a prognostic indicator in patients with papillary renal cell carcinoma.

372 Background: Prognostic indicators in papillary renal cell carcinoma (PRCC) are not well defined. We evaluated the prognostic relevance of tumor-associated macrophages (TAM) in patients with PRCC. Methods: PRCC specimens were re-evaluated by one blinded pathologist (SM), with respect to pT-classification (TNM 2002), nodal status, Fuhrman grade (I-IV), tumor size, subtype (type 1 or 2), tumor necrosis, and presence of TAM. Presence of TAM was associated with pathological parameters (chi-square and fisher's exact tests). Impact of TAM on cancer-specific survival (CSS) was assessed (Kaplan-Meier method and log-rank test). A multivariate regression analysis including pT-stage, grade, vascular invasion, necrosis, tumor size, papillary subtype and TAM was performed with respect to CSS. Results: 177 patients operated for PRCC from 1984 to 2006, were evaluated. Presence of TAM was noted in 112/177 (63%) tumors and was significantly associated with favorable pathological parameters: low pT-classification (pT1a/b: 71/90, 79%; pT2: 14/31, 45%; pT3a/b: 27/56, 48%; p<0.001), node negative tumors (Nx/pN0: 111/170, 65% vs. pN1/2: 1/7, 14%; p=0.01), low grade (G1: 35/45, 78%; G2: 67/110, 61%; G3: 10/22, 45%; p=0.025), absence of vascular invasion (V0: 106/153, 69% vs. V1/2: 6/24, 25%; p<0.001), and papillary subtype (type 1: 64/87, 74% vs. 48/89, 54%; p=0.007), respectively. Median follow-up was 68.3 months. Five-year CSS probabilities for patients with TAM-positive tumors were 93.5%, compared with 72.5% in patients with TAM-negative tumors (p<0.001). Median survival was not reached in both groups. Multivariate analysis revealed node positive tumors (HR=2.4, 95%CI=1.1-5.0; p=0.025), distant metastases (HR=8.7, 95%CI=2.6-29.3; p<0.001), and tumor size (HR=1.2, 95%CI=1.0-1.3; p=0.03) as independent predictors of death from PRCC, whereas presence of TAM was independently associated with favorable outcome (HR=0.3, 95%CI=0.1-0.9, p=0.026). Conclusions: Presence of TAM was independently associated with a favorable outcome in patients with PRCC and was shown to reduce the risk of death from cancer by 66%. Presence of TAM should therefore be part of routine pathology reporting in PRCC. No significant financial relationships to disclose.

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Gene expression profiling identifies two distinct papillary renal cell carcinoma (RCC) subgroups of contrasting prognosis

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4503 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4503-4503

Author(s):

B. T. Teh ◽

X. J. Yang ◽

M. Tan ◽

H. L. Kim ◽

W. Stadler ◽

...

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Papillary Renal Cell Carcinoma ◽

Comparative Genomic ◽

Low Grade ◽

Class 1

4503 Background: Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphological classification of PRCC into Type 1 and Type 2 tumors has been recently proposed, but its biological relevance remains uncertain. Methods: We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analysis. Comparative genomic microarray analysis (CGMA) was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples, with 15 independent tumors. Results: We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histological subtypes: Type 1, low-grade Type 2 and mixed Type 1/low-grade Type 2 tumors. The second class, with poor survival, corresponded to high-grade Type 2 tumors (n = 11). Dysregulation of G1/S and G2/M checkpoint genes were found in Class 1 and Class 2 tumors respectively, alongside characteristic chromosomal aberrations. We identified a 7-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in Class 1 tumors, and of topoisomerase IIα in Class 2 tumors. Conclusions: We report two molecular subclasses of PRCC, which are biologically and clinically distinct, which may be readily distinguished in a clinical setting. This may also have therapeutic implications. No significant financial relationships to disclose.

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