Fuhrman Grade Provides Higher Prognostic Accuracy Than Nucleolar Grade for Papillary Renal Cell Carcinoma

Klatte, Tobias; Anterasian, Christine; Said, Jonathan; Martino, Michela de; Belldegrun, Arie S.

doi:10.1016/j.juro.2010.02.023

Cited by 31 publications

(19 citation statements)

References 28 publications

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“…Many studies have confirmed that Fuhrman grade is correlated with RCC prognosis (20). Recent research found that the Fuhrman grade also provides independent prognostic information for papillary RCC patients (21). We found that TPM1 expression was associated synchronously with both the Fuhrman grade and prognosis in the participating RCC patients.…”

Section: Discussionsupporting

confidence: 48%

Clinical and tumor significance of tropomyosin-1 expression levels in renal cell carcinoma

Wang

Jin

et al. 2015

Oncology Reports

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Abstract. Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and has been described as one of the deadliest of cancers affecting the genitourinary tract. Tropomyosin is a two-stranded α-helical coiled coil protein found in cell cytoskeletons. One of its isoforms, tropomyosin-1 (TPM1) has been reported as a novel tumor-suppressor gene and is downregulated in many solid tumors. However the expression level and function of TPM1 in RCC have not yet been determined. In the present study, we evaluated the TPM1-4 mRNA and TPM1 protein levels in RCC tissue samples. TPM1-overexpressing OSRC-2 and 786-O cell lines were also used to investigate the impact of TPM1 on RCC cells. We found that TPM1 was significantly and specifically downregulated in the RCC tissues. TPM1 expression was associated with tumor size, smoking status, Fuhrman grade and the prognosis of RCC patients. After TPM1 transfection, the migratory and invasive abilities of the OSRC-2 and 786-O cell lines were both reduced when compared to the control groups. Meanwhile, apoptosis was also enhanced in these two RCC cell lines following TPM1 transfection. Taken together, TPM1 exhibits characteristics of a tumor-suppressor gene while being overexpressed in RCC cell lines. IntroductionRenal cell carcinoma (RCC), which originates from renal tubular epithelial cells, accounts for 80-85% of all cases of kidney cancer, and is responsible for ~2-3% of all malignant diseases in adults (1). The overall 5-year survival of RCC is as low as 20-25%, and the most important factor in the selection of the appropriate therapy for RCC patients is the presence of metastases (2).Tropomyosin (TPM) is an important component of microfilaments, a cytoskeleton structure, and is mainly involved in the contraction of skeletal and smooth muscle cells or maintaining the stability of the cytoskeleton in non-muscular cells (3). Four tropomyosin genes, TPM1, TPM2, TPM3 and TPM4, have been confirmed in mammals including humans. More than 20 isoforms can be produced through alternative splicing. All of these homologous isoforms fold into two parallel, linear chains of spiral α-helices (4). These TPM proteins are involved in the regulation of many benign myopathies, such as myasthenia gravis and familial hypertrophic cardiomyopathy (5). Additionally, other studies have discovered that TPM1 plays an important role as a tumor-suppressor gene (TSG) in tumor occurrence and progression (6,7). Recently, evidence indicates that TPM1 could be a novel target gene of microRNA-21 which was found to be upregulated in many different solid tumors, including RCC (8). However, whether or not TPM1 serves as a tumor-suppressor gene in RCC and is selectively downregulated during RCC development has not been determined. Therefore, in the present study, we investigated the expression level of TPM1 in a set of RCC tissue samples and further evaluated its tumor-suppressing activities in two RCC cell lines (786-O and OSRC-2). Materials and methodsTissue samples. Ninety-eight tissue samples in...

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Section: Discussionsupporting

confidence: 48%

Clinical and tumor significance of tropomyosin-1 expression levels in renal cell carcinoma

Wang

Jin

et al. 2015

Oncology Reports

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“…The prognostic value of Fuhrman grading in PRCC has been reported, but results have been inconsistent, with only a few studies revealing statistical prognostic significance, particularly on multivariate analysis [6,12,19,21,[32][33][34]. Many pathologists rely solely on nucleolar prominence when grading RCC, rather than applying the full Fuhrman grading criteria [10,11].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the 3 components of the Fuhrman system were assessed independently for prognostic significance, and only nucleolar prominence was retained on multivariate analysis in PRCCs, proposing the use of nucleolar grading instead of Fuhrman grading for PRCC [11]. However, an additional study revealed the Fuhrman grade to be statistically superior to nucleolar grade [12].…”

Section: Introductionmentioning

confidence: 99%

Papillary renal cell carcinoma: correlation of tumor grade and histologic characteristics with clinical outcome

Cornejo¹,

Dong²,

Zhou³

et al. 2015

Human Pathology

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“…In the largest study of a series of P-RCCs to date, Sukov et al (n=395; including 252 type 1 and 143 type 2 tumors) demonstrated that while both Fuhrman nuclear grade and P-RCC subtype were predictive of death from RCC on univariate analysis (Fuhrman nuclear grade HR 4.0, p<0.001; P-RCC subtype HR 2.2, p=0.01), only Fuhrman nuclear grade retained statistical significance on multivariate analysis including tumor stage (Fuhrman nuclear grade HR 2.8, p=0.001; P-RCC subtype HR 0.86, p=0.66)[11]. Klatt et al and Siki-Paotonu et al similarly showed grade to be more predictive of outcome than subtype on multivariate analysis in large series[9,10]. …”

Section: Discussionmentioning

confidence: 99%

“…In an outcome study of P-RCCs, Allory et al found that subtyping was problematic in 35% of cases; 9% of cases were thus not classified as type 1 or type 2, but were instead designated as an oncocytoid type[6]. Furthermore, most studies recognize that type 1 P-RCCs may demonstrate high nuclear grade, despite being classically associated with low grade and relatively indolent behavior[1,4–6,9–11]. …”

Section: Introductionmentioning

confidence: 99%

Papillary renal cell carcinoma revisited: a comprehensive histomorphologic study with outcome correlations

et al. 2014

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Papillary renal cell carcinoma (P-RCC) is the second most common type of malignant renal epithelial tumor, and can be subclassified into type 1, which demonstrates simple cuboidal low-grade epithelium, and type 2, which demonstrates pseudostratified high grade epithelium with abundant eosinophilic cytoplasm. Despite this clinically useful subclassification, P-RCCs exhibit considerable histomorphologic diversity, with many cases having features differing from classically described type 1 and type 2 tumors. To our knowledge, there has been no recent study which has methodically evaluated the histomorphologic features of a series of P-RCCs. To address this, we evaluated a cohort of P-RCCs diagnosed between 1997 and 2004 with long term clinical follow-up data (n=56). Histomorphologic features previously described in the spectrum of type 1 and type 2 P-RCCs were recorded for each tumor, including nuclear grade, complete tumor capsule, and cytoplasmic eosinophilia, as well as several other features. The current TNM staging (AJCC 7th edition) was assigned to all cases. Histomorphologic features were diverse, demonstrating classic type 1 P-RCC and classic type 2 P-RCC morphology, and several tumors with non-classical features. Four patients in this cohort had distant metastasis. The primary tumor was equally divided between type 1 (2 cases) and type 2 (2 cases) morphology in the cases with metastasis. All P-RCC cases with metastases demonstrated presence of high nuclear grade and high tumor stage in the primary tumor. Cluster analysis using staging parameters and histomorphologic features divided tumors into two primary clusters. All primary tumors associated with metastasis were in the same cluster.

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Fuhrman Grade Provides Higher Prognostic Accuracy Than Nucleolar Grade for Papillary Renal Cell Carcinoma

Cited by 31 publications

References 28 publications

Clinical and tumor significance of tropomyosin-1 expression levels in renal cell carcinoma

Clinical and tumor significance of tropomyosin-1 expression levels in renal cell carcinoma

Papillary renal cell carcinoma: correlation of tumor grade and histologic characteristics with clinical outcome

Papillary renal cell carcinoma revisited: a comprehensive histomorphologic study with outcome correlations

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