Junji Yonese

Adult Xp11 Translocation Renal Cell Carcinoma Diagnosed by Cytogenetics and Immunohistochemistry

Purpose: To determine the incidence of Xp11 translocation renal cell carcinoma (RCC) in adult patients using cytogenetics and immunohistochemstry. Experimental Design: Cytogenetic studies were prospectively done using tumor samples from 443 consecutive adult Japanese patients (ages 15-89 years) who underwent nephrectomy for RCC. TFE3 immunohistochemistry was done for cases in which cytogenetic results were not obtained. Clinicopathologic characteristics of Xp11 translocation RCC were examined. Results: Mitotic cells suitable for cytogenetic analysis were obtained in 244 tumor samples (55%); among these, we identified 4 cases (1.6%) of Xp11 translocation RCC. TFE3 immunohistochemistry identified 3 positive cases (1.5%) among the remaining 199 cases. The median age of the 7 patients was 41 years (range, 15-59 years), and 15% of RCC patients (4 of 26) who were younger than ages 45 years had this type of RCC. Of the four Xp11 translocation RCC patients whose karyotypes were determined, two had an ASPL-TFE3 gene fusion. Of these 2, 1 had pulmonary metastasis at presentation, and the other developed liver metastasis 12 months after nephrectomy and died of the disease. The remaining two patients had PRCC-TFE3 and PSF-TFE3 gene fusions, respectively. Both had nodal involvement but remained disease free for 3 and 5 years, respectively, after surgical resection of lymph node metastases. Of the 3 immunohistochemically diagnosed patients, 1 had nodal metastases at presentation and died 9 months after surgery. Conclusions: This is the first report to determine the incidence of Xp11 translocation RCC in adult patients. We found that this disease is relatively common in young adults.

Incidence of Benign Pathologic Lesions at Partial Nephrectomy for Presumed RCC Renal Masses: Japanese Dual-Center Experience with 176 Consecutive Patients

OBJECTIVES To determine the incidence of benign pathologic findings at elective partial nephrectomy for renal masses thought to be renal cell carcinoma (RCC) on preoperative imaging in Japanese patients. METHODS From 1993 to 2007, 176 patients (46 women and 130 men) underwent elective partial nephrectomy for presumed RCC masses in 2 Japanese centers. The mean size of the resected lesions was 2.3 cm (range 0.3-5.8). Overall, 97 and 79 patients had a renal mass of < or = 2 cm and > 2 cm, respectively. Of the 176 patients, 100%, 89%, and 32% had preoperatively undergone computed tomography, ultrasonography, and magnetic resonance imaging, respectively. RESULTS Of the 176 masses resected, the pathologic examination revealed benign findings in 19 (11%), angiomyolipoma in 10 (5.7%), oncocytoma in 5 (2.8%), complicated cysts in 2 (1.1%), and a solitary fibrous tumor and scar of the kidney 1 each (0.6%). Of the 46 women, 12 (26.1%) had benign lesions compared with 7 of the 130 men (5.3%; P = .0003). Of the 10 angiomyolipomas diagnosed, 8 were diagnosed in women (P = .0004). Tumor size was not associated with benign histologic findings. The incidence of benign lesions was equivalent (10% and 12%) between the 2 centers. CONCLUSIONS The present incidence (11%) of benign lesions in presumed RCC masses at surgery in Japanese patients was lower than the incidence of 20%-30% previously reported from Western countries, probably because of the low incidence of oncocytomas in Japanese patients. Women had almost 5 times the likelihood of having a benign lesion compared with men, because of the high incidence of angiomyolipomas in women.

Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method.

Several promising molecular‐targeted drugs are used for advanced renal cancers. However, complete remission is rarely achieved, because none of the drugs targets a key molecule that is specific to the cancer, or is associated with “oncogene addiction” (dependence on one or a few oncogenes for cell survival) of renal cancer. Recently, an anaplastic lymphoma kinase (ALK) fusion, vinculin‐ALK, has been reported in pediatric renal cell carcinoma (RCC) cases who have a history of sickle cell trait. In this context, ALK inhibitor therapy would constitute a therapeutic advance, as has previously been demonstrated with lung cancer, inflammatory myofibroblastic tumors, and anaplastic large cell lymphomas.

The serum level of the amino‐terminal propeptide of type I procollagen is a sensitive marker for prostate cancer metastasis to bone

Objective To assess the level of a bone‐formation marker, the amino‐terminal propeptide of type I procollagen (PINP), for its utility in indicating bone metastasis in patients with prostate cancer.

Development and External Validation of a New Outcome Prediction Model for Patients With Clear Cell Renal Cell Carcinoma Treated With Nephrectomy Based on Preoperative Serum C-Reactive Protein and TNM Classification: The TNM-C Score

PURPOSE C-reactive protein has been shown to be a prognostic factor for renal cell carcinoma. We developed a new prediction model including C-reactive protein in patients with clear cell renal cell carcinoma. MATERIALS AND METHODS This study is based on 2 cohorts of Japanese patients with clear cell renal cell carcinoma, including 249 for evaluating prognostic factors and developing the prediction model, and 290 for external validation. Analyzed factors included TNM classification, tumor size, Fuhrman nuclear grade, tumor necrosis and preoperative serum C-reactive protein (cutoff 0.5 mg/dl). We developed a scoring model based on multivariate analysis to predict cancer specific survival. Predictive ability of the model was evaluated using the concordance index. RESULTS Multivariate analysis showed that pT stage, lymph node involvement, distant metastasis, tumor necrosis and C-reactive protein were independent predictors of cancer specific survival. A new scoring model was developed, consisting of C-reactive protein and the TNM classification. The 5-year cancer specific survival rate in patients with a score of 0, 1 and 2, 3 and 4, and 5 or more was 99%, 89%, 69% and 18%, respectively. Cancer specific survival rates were clearly discriminated by the stratification according to the scoring model (p <0.001). The concordance index of the new model was 0.820, which was externally validated as a concordance index of 0.865. CONCLUSIONS In patients with clear cell renal cell carcinoma a new simple scoring model based on serum C-reactive protein and the TNM classification is a useful and easy to use tool for predicting outcome.

Development, Validation, and Head-to-Head Comparison of Logistic Regression-Based Nomograms and Artificial Neural Network Models Predicting Prostate Cancer on Initial Extended Biopsy

OBJECTIVES Using cohorts examined by extended biopsy, we developed and validated multivariate models predicting prostate cancer on initial biopsy and examined whether these extended biopsy-based models outperform previously established models. METHODS Initial extended biopsy (median 22 cores) was performed in 1509 Japanese men including 1083 at Tokyo Medical and Dental University Hospital (TMDU) and 426 at Cancer Institute Hospital (CIH). Logistic regression-based nomograms 1 and artificial neural network (ANN) 1 incorporating age, digital rectal examination, and prostate-specific antigen (PSA) and free PSA, and nomogram 2 and ANN2 further incorporating transrectal ultrasound (TRUS) findings and prostate volume were constructed on the TMDU data. These and previously established models were externally validated on the CIH data set and predictive accuracy was compared directly. RESULTS Without TRUS-derived information, nomogram 1 outperformed the ANN1. With TRUS-derived information, nomogram 2 was more accurate than ANN2. External validation revealed applicability of the Western models to Japanese population, superiority of the nomograms over ANN models, and better predictive accuracy of our extended biopsy-based nomograms than the previous 6-10-core biopsy-based models. Using nomograms 1 and 2, 16% and 19% unnecessary biopsies would be saved at 95% sensitivity. CONCLUSIONS We developed new nomograms predicting prostate cancer on initial biopsy in men with PSA <20ng/ml. Predictive accuracy of these extended biopsy-based nomograms is better than those of previously established models based on 6-10-core biopsies. Our models might help clinicians to decide if a patient requires biopsy and to avoid unnecessary biopsies.

Radiotherapy to bone metastases from renal cell carcinoma with or without zoledronate

To investigate the rate of objective response and the skeletal‐related event (SRE)‐free survival after combined therapy with radiotherapy (RT) and zoledronate in patients with bone metastases from renal cell carcinoma (RCC).

Diverse Fusion Patterns and Heterogeneous Clinicopathologic Features of Renal Cell Carcinoma With t(6;11) Translocation

Renal cell carcinoma (RCC) with t(6;11) translocation, involving the transcription factor EB (TFEB) and Alpha, also known as MALATI, (TFEB RCC), is extremely rare, with only 20 cases reported to date. It may be frequently misdiagnosed because of a lack of established characteristics. TFEB RCCs are predominantly seen in younger patients and are generally indolent, with only 2 cases of metastasis. Genetic analysis has been limited, showing break points upstream of TFEB exon 3, yielding only a single transcript. We examined 3 new adult Japanese TFEB RCC cases by means of precise clinicopathologic, immunohistochemical, cytogenetic, and molecular analyses and compared them with 200 ordinary RCCs. A 57-year-old man was the oldest patient with TFEB RCC at the time of this study. Although the tumor had histology typical of translocation RCC, its fusion points were different between the genomic and transcript coordinates. A 37-year-old man had an aggressive course resulting in death. The tumor had 2 variants of messenger ribonucleic acid. A 47-year-old man showed borderline histologic and immunohistochemical features between TFEB RCC and chromophobe-type RCC. The tumor had a fusion point in TFEB exon 4, downstream of the wild-type ATG in exon 3. Nuclear expression of the TFEB protein was detected, and a Western blotting analysis identified a protein similar in size to the wild-type TFEB protein. Immunohistochemistry is useful for the diagnosis of these tumors, and TFEB RCCs have heterogeneous clinicopathologic features and more diverse fusion patterns than previously thought, requiring attention to polymerase chain reaction experiments for diagnosis. Our study will contribute to the correct diagnosis of TFEB RCC.

Prognostic Impact of C-reactive Protein for Determining Overall Survival of Patients With Castration-resistant Prostate Cancer Treated With Docetaxel

OBJECTIVE To verify the prognostic impact of C-reactive protein (CRP) for patients with castration-resistant prostate cancer (CRPC) treated with docetaxel in a single institution. METHODS A group of 80 consecutive patients with CRPC were treated with docetaxel in our institution from January 2005 to May 2010. The patients received 75 mg/m(2) of docetaxel intravenously every 3 weeks. The prognostic value of all covariables, including CRP, was assessed using the Cox proportional hazard model. Risk stratification for overall survival was described from the results of the multivariable analysis. RESULTS The median survival period for all patients was 14.5 months. The multivariable analysis showed that CRP and hemoglobin levels were independent prognostic factors for overall survival. Based on the presence of an elevated CRP concentration and/or a low hemoglobin level, all patients were stratified into 3 risk groups: those with no risk factors (low-risk group), those with 1 risk factor (intermediate-risk group), and those with 2 risk factors (high-risk group). The overall survival curves were clearly tiered according to the risk groups, with the 1-year overall survival rates being 86.3%, 60.5%, and 23.0% for the low-, intermediate-, and high-risk groups, respectively (P <.001). CONCLUSION CRP is an independent prognostic factor for overall survival of patients with CRPC treated with docetaxel. Risk stratification based on CRP and hemoglobin could be helpful for estimating the overall survival.

Characteristics and clinical significance of prostate cancers missed by initial transrectal 12-core biopsy

Study Type – Diagnostic (exploratory cohort)