Significant Decrease In Disease-free Survival Research Articles

Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma.

To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC). We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery. Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n= 51) was 39.2% (95% confidence interval [CI]: 25.3%-53.1%), and for patients with a low expression (n= 59), it was 63.6% (95% CI: 51.1%-76.1%) (p= 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p= 0.086). In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival.

Validation of the 2018 FIGO Classification for Cervical Cancer: Lymphovascular Space Invasion Should Be Considered in IB1 Stage.

Simple SummaryThe purpose of modifying a tumor staging system is to incorporate already well-established prognostic factors, allowing one to stratify cases and leading to tailored treatment approaches. Although lymphovascular space invasion (LVSI) has been described as an independent risk-factor of recurrence in early-stage cervical cancer and defined intermediate and high-risk cervical cancer according to the ESGO (European Society of Gynaecological Oncology) guidelines, this factor remains controversial and was not included in the last revised 2018 International Federation of Gynecology and Obstetrics (FIGO) classification. The aim of the present study was to determine whether LVSI has an impact on the prognosis of IB1 patients according to 2018 FIGO classification through two French prospective multicentric cohorts. Our results highlighted that LVSI was associated with a significantly decreased 5-year DFS in IB1 2018 FIGO stage compared to negative LVSI. Particular attention should be paid to LVSI status in early-stage cervical cancer for a more precise risk assessment and we suggest that LVSI may be considered in the new 2018 FIGO classification.Background: The aim of this study was to assess the prognostic impact of Lymphovascular space invasion (LVSI) in IB1 stage of the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) classification for cervical cancer. Methods: A secondary analysis of two French prospective multicentric trials on Sentinel Lymph node biopsy for cervical cancer was performed. Patients with 2009 FIGO IB1 stage who underwent radical surgery between January 2005 and July 2012 from 28 French expert centers were included. The stage was modified retrospectively according to the new 2018 FIGO staging system. Results: According to the 2009 FIGO classification, 246 patients had IB1 disease stage and fulfilled the inclusion criteria. The median follow-up was 48 months (4–127). Twenty patients (8.1%) experienced a recurrence, and the 5-year Disease Free Survival (DFS) was 90.0%. Compared to 2018 IB1 staged patients, new IB2 had significantly decreased 5-year DFS, 78.6% vs. 92.9%, p = 0.006 whereas IIIC patients had similar 5-year DFS (91.7%, p = 0.95). In the subgroup of patients with FIGO 2018 IB1 stage, the presence of LVSI was associated with a significant decrease in DFS (82.5% vs. 95.8%, p = 0.04). Conclusions: LVSI is associated with decreased 5-year DFS in IB1 2018 FIGO stage and LVSI status should be considered in early-stage cervical cancer for a more precise risk assessment.

GPD1L is negatively associated with HIF1α expression and predicts lymph node metastasis in oral and HPV- Oropharyngeal cancer.

The study is to determine if Glycerol-3-phosphate dehydrogenase 1-like (GPD1L) and hypoxia-inducible factor-1α (HIF1α) can identify high-risk patients with delayed lymph node metastasis in early-stage head and neck squamous cell carcinoma (HNSCC). The mRNA and protein expressions of markers were analyzed using fresh and paraffin embedded HNSCC specimens. The statistical analyses included chi-squared test, t test, correlation analysis, and univariate and multivariate analyses. GPD1L (downregulated) and HIF1α (upregulated) mRNA expression had a negative correlation (r=-.496, p=.001) in cT1-2N0 HNSCC. The low GPD1L+high HIF1α expression group (22.6%) showed a significant decrease in disease-free survival compared with the high GPD1L+low HIF1α expression group (71.4%) in the neck dissection group. The low GPD1L+high HIF1α expression (39.4%) resulted in a significantly higher delayed metastasis rate than the high GPD1L+low HIF1α expression (5.6%) for cT1-2N0 HNSCC in the neck observation group. GPD1L and HIF1α protein expression more accurately predicted lymph node metastasis than the WINTER hypoxia gene panel (false-negative rate in predicting metastasis: 8.1% versus 26.4%). Cox regression analyses found that the combined protein expression of GPD1L and HIF1α could predict delayed metastasis (HR:0.118, 95% CI:0.027-0.525). Low GPD1L+high HIF1α expression can serve as candidate biomarkers for high-risk populations with lymph node metastases in early-stage HNSCC.

Radiation Treatment Breaks: Are They Detrimental to Outcomes for Oropharyngeal Carcinoma Treated with Definitive Chemoradiation?

Varying practices exist to account for radiation treatment breaks (rTBs) resulting from institutional holidays during treatment of oropharyngeal squamous cell carcinoma (OPSCC) cancer patients undergoing concurrent chemoradiation (CRT). Studies in radiation biology suggest that local therapy delays may result in accelerated repopulation of residual tumor cells, however the clinical effects of this model in the setting of concurrent systemic therapy are unclear. We, therefore, evaluated the effect of rTBs in patients who received CRT on disease-free survival (DFS) in a consecutive cohort of patients with OPSCC. Patients with recurrent OPSCC, M1 disease, less than 6 months follow-up, or those treated with surgery or RT alone were excluded. Data collected included age, sex, KPS, smoking status, T stage, N stage, p16 IHC or HPV ISH status, RT dose and fractions, systemic therapy, total treatment duration, number of total and cumulative rTBs, overall survival/local/regional/distant failure (calculated from start of RT). rTBs were defined as any breaks taken during RT. Cumulative rTBs were defined as largest number of consecutive rTBs, not including weekends. The Kaplan-Meier method was used to estimate time-to-event outcomes on univariate analysis (UVA) and the Cox proportional hazards model was used to determine the effects of covariates on multivariate analysis (MVA). 462 OPSCC patients meeting inclusion criteria treated between 1/1/2010 and 12/31/2015. Median follow up was 5 years (6 months -10 yrs). Median total treatment duration was 48 days (41-64 days). 457 (99%) patients received 70 Gy of RT, 1 patient received a 400 cGy boost, and 4 patients received 66-68 Gy. 54 (12%) patients received induction chemotherapy. 369 (80%) patients received a cisplatin-based regimen and 93 (20%) received a non-cisplatin regimen. 345 (75%) were HPV or p16 positive, 45 (10%) were negative, and 72 (15%) were unknown. Table 1 describes the rTBs experienced by our cohort and results of our analysis. On UVA, only cumulative rTBs of 3 days were found to be significant (p = 0.04). On MVA, however, treatment duration, total rTBs, and cumulative rTBs were not significantly associated with DFS. We did not find a significant decrease in DFS for patients who had rTBs of 3 days in the setting of CRT for OPSCC. However, extended consecutive breaks (>3 days) may be associated with poorer outcomes, warranting further investigation.Abstract 3986; TableResults of UVA and MVA for DFSn (%)UVAMVATotal Breaks (days) 0140 (30) 1166 (36)p = 0.21p = 0.63HR 1.68 [0.21-13.65] 279 (17)p = 0.72p = 0.71HR 1.48 [0.19-11.44] 329 (6)p = 0.95p = 0.96HR 0.93 [0.10-9.32] 417 (4)p = 0.41p = 0.51HR 0.42 [0.03-5.70] 5+*31 (7)p = 0.10p = 0.81HR 1.34 [0.12-15.24]Cumulative Breaks (days) 0147 (32) 1256 (55)p = 0.34p = 0.96HR 0.92 [0.12-7.03] 225 (5)p = 0.53p = 0.71HR 1.55 [0.16-14.59] 314 (3)p = 0.04p = 1.00HR 1.00 [0.10-10.03] 410 (2)p = 0.52p = 0.83HR 0.73 [0.04-13.08] 510 (2)p = 0.38p = 65HR 1.83 [0.14-24.79]*Range 5-14 days. Open table in a new tab

TERT Promoter Mutation C228T Increases Risk for Tumor Recurrence and Death in Head and Neck Cancer Patients.

Background: Head and neck squamous cell carcinoma (HNSCC) is usually associated to tobacco and alcohol consumption. Increased telomerase activity has been consistently detected in 80–90% of malignant tumors, including HNSCC. Mutations within the promoter region of telomerase reverse transcriptase (TERT) that confer enhanced TERT promoter activity have been reported in two major hotspots, designated C228T and C250T.Objectives: To evaluate TERT promoter mutations C228T and C250T in HNSCC patients from Brazil and correlate with patients' outcome.Materials and Methods: Formalin-fixed paraffin-embedded tissues were obtained from 88 HNSCC patients and analyzed for TERT promoter mutations C228T and C250T by pyrosequencing.Results: The overall prevalence of hotspot TERT mutations in HNSCC samples was of 27.3%, with 6.8% at locus C228T and 20.5% at C250T. The majority (92%) of mutated cases were located in oral cavity, mainly at the tongue. We observed that 94.4% of the patients harboring TERT promoter mutation C250T were alcohol consumers (p = 0.032) and 66.7% of the patients harboring TERT promoter mutation C228T were not alcohol consumers (p = 0.035). The presence of C228T mutation impacted patient outcome, with a significant decrease in disease-free survival (20.0 vs. 63.0%, p =0.017) and in overall survival (16.7 vs. 45.1%, p = 0.017).Conclusion: This is the first report of a TERT promoter mutations in HNSCC patients from South America. The high prevalence of TERT mutation, as well as its association with poor disease-free survival and overall survival, particular at C228T locus might serve as a prognostic biomarker in HNSCC to help clinicians in the management of treatment.

Impact of micrometastasis or isolated tumor cells on recurrence and survival in patients with early cervical cancer: SENTICOL Trial.

The aim of this study was to evaluate the impact of micrometastasis and isolated tumor cells on disease recurrence in patients with early-stage cervical cancer. We included patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA1 with lymphvascular space invasion, stage IA2, and IB1 who participated in the SENTICOL1 trial. A centralized histologic analysis with re-reading and ultrastaging was performed 3 months after surgery and treatment was not impacted by findings from our study. Patients were followed for 3 years and outcomes were compared according to prognostic factors. A total of 139 patients were included and 13 recurrences were found. There were two recurrences in patients with positive sentinel lymph node (SLN) (one macrometastases and one micrometastases) and 11 recurrences in patients with negative lymph nodes (sentinel or non-sentinel). Among patients with positive SLN for micrometastases there was only one recurrence. No patient with isolated tumor cells on their lymph nodes experienced a recurrence. There was a significant decrease in disease-free survival in patients aged >50 years (p = 0.01). Evidence of micrometastasis or isolated tumor cells in the SLN of untreated patients with early cervical cancer in the SENTICOL1 trial did not impact progression-free survival.

Significance of intratissue estrogen concentration coupled with estrogen receptors levels in colorectal cancer prognosis.

Dysregulation of estrogen related pathways is implicated colorectal cancer (CRC) development. However, significance of intratissue concentration of estrone (E1) and 17β-estradiol (E2) in relation to estrogen receptor (ESR) expression level was not addressed so far. Herein, we measured E1 and E2 intratissue concentration using liquid chromatography electrospray ionization tandem mass spectrometry (ESI LC/MS) and mRNA levels of ESR1 and ESR2 using RT-qPCR in cancerous and histopathologically unchanged tissue from 75 and 110 CRC patients, respectively. The obtained results were associated with clinicopathological factors, expression of estrogen dependent genes (CTNNB1, CCND1) and prognostic significance. We found no statistically significant differences in E1 or E2 concentration between cancerous tissue and histopathologically unchanged counterparts. Moreover, mRNA levels of ESR1 and ESR2 were significantly decreased in cancerous tissue compared with histopathologically unchanged (p=0.00001). Log rank analysis revealed no benefit of low E1 to E2 ratio, high E1, E2 concentration or ESR1, ESR2 mRNA level for patients’ overall (OS) and disease free survival (DFS). Interestingly, we have observed that patients with low ESR1 mRNA level coupled with low E1 intratissue concentration had a significant decrease in DFS compared with group of patients with high ESR1 mRNA level and high E1 concentration (HR=0.16, 95% CI 0.02-1.05; p=0.06). Furthermore, patients with low E1 concentration and low ESR1 transcript had significantly higher CTNNB1 and CCND1 mRNA level compare with subgroup with high level of both grouping factors. Our study indicates a potential value of estrogen intratissue concentration and its receptor expression level for CRC patients’ prognosis.

S100A11 is a potential prognostic marker for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of few cancers with rising incidence in North America. The prognosis of ccRCC is variable and difficult to predict. Stratification of patients according to disease aggressiveness can significantly improve patient management. We investigated the expression of the S100A11 protein in 385 patients with primary ccRCC using immunohistochemistry on tissue microarrays. We compared its expression with clinicopathologic parameters and patients’ survival. We also validated our results at the mRNA level on an independent set from The Cancer Genome Atlas. As a dichotomous variable (low vs. high expression), there was a significant association between S100A11 expression and tumor grade, with higher expression associated with higher tumor grades (p < 0.001). High expression was also significantly more frequently seen in higher versus lower stages (56 vs. 28 %). In the univariate analysis, high S100A11 expression was associated with significantly shorter disease-free survival (DFS) (HR = 2.28; p = 0.001). This was maintained in the multivariate analysis (HR = 1.69; p = 0.042). Expression was not associated with overall survival (OS) (p = 0.10). Comparable results were obtained when S100A11 expression was analyzed as a trichotomous variable (low, moderate, or high expression). The Kaplan–Meier survival analyses showed that higher S100A11 expression was associated with statistically significant decrease in DFS (p < 0.001), but not OS (p = 0.1).

PTEN Loss Is Associated with Worse Outcome in HER2-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance.

To investigate the clinical relevance of PTEN in HER2-amplified and HER2-nonamplified disease. We assessed PTEN status in two large adjuvant breast cancer trials (BCIRG-006 and BCIRG-005) using a PTEN immunohistochemical (IHC) assay that was previously validated in a panel of 33 breast cancer cell lines and prostate cancer tissues with known PTEN gene deletion. In the HER2-positive patient population, absence of tumor cell PTEN staining occurred at a rate of 5.4% and was independent of ER/PR status. In contrast, 15.9% of HER2-negative patients exhibited absence of PTEN staining with the highest frequency seen in triple-negative breast cancer (TNBC) subgroup versus ER/PR-positive patients (35.1% vs. 10.9%). Complete absence of PTEN staining in tumor cells was associated with poor clinical outcome in HER2-positive disease. Those patients whose cancers demonstrated absent PTEN staining had a significant decrease in disease-free survival (DFS) and overall survival (OS) compared with patients with tumors exhibiting any PTEN staining patterns (low, moderate, or high). Trastuzumab appeared to provide clinical benefit even for patients lacking PTEN staining. In the HER2-negative population, there were no statistically significant differences in clinical outcome based on PTEN status. This study is the largest to date examining PTEN status in breast cancer and the data suggest that the rate and significance of PTEN status differ between HER2-positive and HER2-negative disease. Furthermore, the data clearly suggest that HER2-positive patients with PTEN loss still benefit from trastuzumab.

Triple Negative Breast Tumors in African-American and Hispanic/Latina Women Are High in CD44+, Low in CD24+, and Have Loss of PTEN

BackgroundAfrican-American women have higher mortality from breast cancer than other ethnic groups. The association between poor survival and differences with tumor phenotypes is not well understood. The purpose of this study is to assess the clinical significance of (1) Stem cell-like markers CD44 and CD24; (2) PI3K/Akt pathway associated targets PTEN, activation of Akt, and FOXO1; and (3) the Insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP3) in different breast cancer subtypes, and compare the differences between African-American and Hispanic/Latina women who have similar social-economic-status.MethodsA total of N=318 African-American and Hispanic/Latina women, with clinically-annotated information within the inclusion criteria were included. Formalin fixed paraffin embedded tissues from these patients were tested for the different markers using immunohistochemistry techniques. Kaplan-Meier survival-curves and Cox-regression analyses were used to assess Relative Risk and Disease-Free-Survival (DFS).ResultsThe triple-negative-breast-cancer (TNBC) receptor-subtype was more prevalent among premenopausal women, and the Hormonal Receptor (HR) positive subtype was most common overall. TNBC tumors were more likely to have loss of PTEN, express high Ki67, and have increased CD44+/CD24- expression. TNBC was also associated with higher plasma-IGF-I levels. HR-/HER2+ tumors showed high pAkt, decreased FOXO1, and high CD24+ expression. The loss of PTEN impacted DFS significantly in African Americans, but not in Hispanics/Latinas after adjusted for treatment and other tumor pathological factors. The CD44+/CD24- and CD24+/CD44- phenotypes decreased DFS, but were not independent predictors for DFS. HER2-positive and TNBC type of cancers continued to exhibit significant decrease in DFS after adjusting for the selected biomarkers and treatment.ConclusionsTNBC incidence is high among African-American and Hispanic/Latino women residing in South Los Angeles. Our study also shows for the first time that TNBC was significantly associated with PTEN loss, high Ki67 and the CD44+/CD24- phenotype. The loss of PTEN impacts DFS significantly in African Americans.

The anti-adhesive mucin podocalyxin may help initiate the transperitoneal metastasis of high grade serous ovarian carcinoma

High grade serous ovarian tumors often metastasize transperitoneally, a process that begins when small tumor nodules de-adhere and are released into the fluid of the abdominal cavity where they float freely to reach new sites on the peritoneal wall. Podocalyxin, a small anti-adhesive sialomucin, has been shown to contribute to non-adhesive membrane domain formation in some epithelia and is overexpressed in a variety of cancers. We therefore assessed podocalyxin expression on a previously characterized tissue microarray and found that 87% (169/194) of high grade serous epithelial ovarian carcinomas were positive for podocalyxin. In addition, cell surface localization of podocalyxin was associated with a significant decrease in disease-free survival in these tumors. When podocalyxin was force-expressed in serous ovarian carcinoma-derived OVCAR-3 cells it was targeted to the cell surface and it decreased the adhesion of these cells to mesothelial monolayers, fibronectin and immobilized β1 integrin-binding antibodies. This decrease in adhesion was associated with a modest decrease in cell surface β1 integrin. In monolayer culture, podocalyxin was targeted to the free, apical domains of OVCAR-3 cells and it appeared to decrease β1 integrin levels on the attached basolateral domains of the same cells. Furthermore, in 3-dimensional basement membrane gel culture, the cells formed small, cohesive nodules and podocalyxin localized to membrane domains at the cell-basement membrane interface. Therefore, podocalyxin's ability to facilitate the formation of non-adhesive membrane domains may contribute to the formation of free-floating high grade serous tumor nodules during the initial steps of transperitoneal metastasis.

Clinical significance of circulating tumor cells detected by an invasion assay in peripheral blood of patients with ovarian cancer

Objectives The invasive growth of circulating tumor cells (CTCs) propagates cancer metastasis. The aims of this study were to evaluate the association of invasive CTCs, detected by a novel cell invasion assay, with disease stage, CA-125 level and patient survival. Methods Peripheral blood samples from 71 patients undergoing evaluation for ovarian malignancy were assessed for the presence of invasive CTCs using a cell invasion assay that enriches and identifies tumor cells with a cell adhesion matrix (CAM). Invasive CTCs were identified as cells exhibiting CAM invasion (CAM+) and expressing standard epithelial markers (Epi+). Results 43 (60.6%) patients had detectable CTCs: 0/5 benign patients, 1/10 (10%) early stage, 39/52 (73.1%) late stage and 3/4 (75%) unstaged patients ( p-value < 0.001). CTC counts ranged from 0–149 CTCs/ml with stage III/IV patients exhibiting significantly higher mean counts (41.3 CTCs/ml) than stage I/II patients (6.0 CTCs/ml) and benign patients (0 CTCs/ml, p-value = 0.001). A positive correlation between CTC count and CA-125 level was observed (Spearman correlation coefficient r = 0.309, p-value = 0.035). Kaplan–Meier curves revealed a significant decrease in disease-free survival in patients with detectable CTCs (median survival 15.0 months vs. 35.0 months, log-rank p-value = 0.042). Tumor grade and tumor histology did not influence CTC detection. Conclusions Invasive CTCs can be detected in a majority of epithelial ovarian cancer patients and may predict shorter disease-free survival. Furthermore, higher CTC counts may reflect later stage disease and higher CA-125 levels.

Thymidine phosphorylase expression in tumor-infiltrating macrophages may be correlated with poor prognosis in uterine endometrial cancer

Expression of thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, in several types of malignant tumors has been associated with angiogenesis and an unfavorable prognosis. We performed a retrospective study on the immunohistochemical expression of TP in patients with uterine endometrial cancer to investigate correlations between the expression of TP and the clinicopathologic features and the prognosis. The immunohistochemical staining for TP, CD68 (macrophage/monocyte-specific antibody), and von Willebrand factor was performed in surgically resected specimens from 101 patients with operable endometrial cancer. A semiquantitative grading system was used to examine the staining pattern for TP. Positive staining for both cancer cell and tumor stromal cell TP was noted in 41% of the cases. Most of tumor stromal cells expressing TP were shown to coexpress CD68. High angiogenesis was also associated with TP overexpression in either cancer cells or tumor stromal cells. When stromal macrophages/fibroblasts exhibited high TP expression, independent of whether cancer cells showed the positive TP expression, a significant decrease in disease-free survival and overall survival was observed, which was found to be an independent prognostic factor. Stromal macrophage/fibroblast TP expression remained significant on multivariate analysis. We conclude that (1) TP is present in both cancer cells and stromal macrophages/fibroblasts, (2) high angiogenesis correlated with TP overexpression, (3) TP produced by neighboring tumor-infiltrating macrophages may play a part in the regulation of the local invasion and distant metastatic behavior, and (4) TP overexpression in stromal macrophages/fibroblasts may be associated with a poor prognosis. HUM PATHOL 33:1105-1113. Copyright 2002, Elsevier Science (USA). All rights reserved.

The erbB oncogenes as prognostic markers in oral squamous cell carcinomas

In clinical practice it became clear that conventional prognostic parameters of oral squamous cell carcinomas (OSCC) are of limited value for the prediction of a disease-free survival. The overexpression of erbB oncogenes is of importance for the clinical course of a variety of solid tumors. After discovering amplifications of erbB oncogenes even in OSCC, it was the aim of the present study to clarify the potential of oncogenes as additional prognostic markers. The amplification of the erbB oncogenes in tumorous tissue of 85 OSCC patients was determined using the double-differential polymerase chain reaction. Histologically healthy mucosa in these patients was also studied. In univariate analysis the amplification of erbB oncogenes with clinical and histopathological prognostic parameters was compared. No significant correlation between common prognostic parameters and erbB-2 amplification was found. Patients whose OSCC tissue showed an average gene copy number for erbB-2 of greater than 1.2, for erbB-3 below 0.11, and a ratio of erbB-1 and erbB-2 below 0.31 had a statistically significant decrease in disease-free survival. Even in histologically healthy oral mucosa from tumor patients an amplification of erbB oncogenes was found. ErbB oncogene amplifications in oral squamous cell carcinomas play a significant role as a prognostic factor and seem to be effective in predicting decrease in disease-free survival. Genetic abnormalities in tumor-surrounding tissue support the field cancerization hypothesis.

Renal cell carcinoma. Prognostic significance of morphologic parameters in 121 cases.

Morphologic parameters were correlated with survival in 121 renal cortical neoplasms including 116 carcinomas and five oncocytomas. An increasing nuclear grade was generally correlated with a significant decrease in disease-free survival although no statistical difference was found between nuclear Grade 1 and 2 tumors. Similarly, a higher stage at diagnosis predicted a shorter disease-free survival. Renal vein invasion adversely affected prognosis only for high nuclear grade carcinomas. Papillary and spindled carcinomas, independent of nuclear grade, were associated with a significant decrease in disease-free survival compared to tumors with a solid pattern. Patients with large neoplasms (greater than 10 cm) had a significantly worse disease-free survival than patients with tumors 10 cm or less. The prognostic significance of tumor cell type is less clear. Patients with oncocytomas had the best disease-free survival compared with patients with tumors of other cell types. However, the difference in survival was not statistically significant for low-grade tumors, suggesting that nuclear grade rather than cell type may be the more important determinant.