Recently several low-grade renal cell tumors, distinct from those recognized by the 2004 World Health Organization classification of renal tumors, have been described. These tumors had similar clinicopathologic features, being low-stage tumors with cystic, tubuloacinar, and/or papillary architecture. The tumor cells were low grade with variable amounts of clear cytoplasm that was positive for cytokeratin 7 (CK7), but negative for CD10. Genetic changes characteristic of clear cell or papillary renal cell carcinoma were not seen in these tumors. We investigated the morphologic, immunohistochemical, and genetic features of 36 additional tumors. Immunohistochemistry was carried out for CK7, carbonic anhydrase 9, α-methylacyl-CoA racemase, CD10, TFE-3, and desmin. Interphase fluorescence in situ hybridization was carried out with centromeric probes for chromosomes 3, 7, 17, and a subtelomeric probe for 3p25. Sequencing of von Hippel-Lindau gene and analysis of the methylation status of the promoter region was also carried out in 2 tumors. Thirty-six tumors from 33 patients (mean age: 60.4 , range: 26 to 88; 17 men and 16 women) were studied. Three patients had bilateral tumors and 1 patient had von Hippel-Lindau disease. Follow-up was available in 60% (20/33) of the patients for a mean of 27.4 (range 1 to 85) months. No patient had evidence of the disease after surgery except for the patient with von Hippel-Lindau disease, who was alive with stable disease in the contralateral kidney. All 36 tumors were small (mean size 2.4 cm; range 0.9 to 4.5 cm) and low stage (pT1). The majority was cystic and had prominent fibrous capsule and stroma. The tumors were composed of variable amount of cysts, papillae, tubules, acini, and solid nests. The most characteristic histologic features were branching tubules and acini and anastomosing clear cell ribbons with low-grade nuclei. All tumors were strongly positive for CK7 and variably positive for CA9, but largely negative for CD10, and negative for α-methylacyl-CoA racemase and TFE-3. All but 1 tumor had no gains of chromosomes 7 and 17 and deletion of 3p. Only 1 tumor had low copy number gains of chromosomes 7 and 17. VHL gene mutation and promoter methylation were negative in 2 tumors analyzed. We show that these tumors, which we term as "clear cell tubulopapillary renal cell carcinoma," constitute a unique subtype in the spectrum of renal epithelial neoplasia based on their characteristic morphologic and immunohistochemical features.

These data indicate a possible role for a tomato sauce constituent, possibly lycopene, in the treatment of prostate cancer and warrant further testing with a larger sample of patients, including a control group.

As part of a randomized placebo-controlled study to evaluate the effect of lycopene supplementation on DNA damage in men with prostate cancer, a nonrandomized 5th arm using tomato sauce was included and reported here. Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for 3 weeks (30 mg of lycopene/day) before their scheduled radical prostatectomy. Prostate tissue was obtained as biopsies at baseline and as resected tissue at the time of the prostatectomy. Serum and prostate lycopene, serum prostate specific antigen (PSA) concentrations, and leukocyte DNA 8-OH-deoxyguanosine/deoxyguanosine (8OHdG) were measured at baseline and at the end of the intervention. Cancer cells in paraffin sections of prostate biopsies and postintervention resected tissue were compared for 8OHdG staining and for apoptosis. Adherence to the daily consumption of tomato-based entrees was 81.6% of the intended dose, and serum and prostate lycopene concentrations increased 1.97- and 2.92-fold (P < 0.001), respectively. Mean serum PSA concentrations decreased by 17.5% (P < 0.002) and leukocyte 8OHdG decreased by 21.3% (P < 0.005) after tomato sauce consumption. Resected tissues from tomato sauce-supplemented patients had 28.3% lower prostate 8OHdG compared with the nonstudy control group (P < 0.03). Cancer cell 8OHdG staining of Gleason Score-matched resected prostate sections was reduced by 40.5% in mean nuclear density (P < 0.005) and by 36.4% in mean area (P < 0.018) compared with the presupplementation biopsy. Apoptotic index was higher in hyperplastic and neoplastic cells in the resected tissue after supplementation. These data taken as a whole indicate significant uptake of lycopene into prostate tissue and a reduction in DNA damage in both leukocyte and prostate tissue. Whether reduction in DNA damage to prostate cancer cells is beneficial awaits further research, although reduction in serum PSA concentrations is promising.

Despite well-established criteria, the distinction of uterine leiomyosarcoma from certain variants of benign leiomyoma, particularly bizarre leiomyoma, can be challenging morphologically. Recent studies reported the overexpression of p16 protein in uterine leiomyosarcoma. However, the potential role of immunohistochemistry of p16, p53, and Ki-67 in the differential diagnosis of leiomyosarcoma and bizarre leiomyoma has not been well assessed. We had immunohistochemically studied the expression of p16, p53, and Ki-67 proteins in 100 cases of uterine smooth muscle tumors, including 35 usual leiomyomas (LM), 13 cellular leiomyomas (CLM), 15 bizarre leiomyomas (BLM), 2 cases of smooth muscle tumor of uncertain malignant potential (STUMP), and 35 leiomyosarcoma (LMS). For p16 immunostain, strong and mediate-to-diffuse staining pattern (>25% cells positive) was seen in 100% of LMS and STUMP. There were 86.5% of BLM that showed positive for p16, which includes 60% of them showing mediate-to-diffuse p16 positivity. Although 38.5% of CLM and 14% of usual LM showed p16 positivity, the majority of those (70%) are focal with weak p16 staining pattern. The strong, mediate-to-diffuse p53 immunostain was seen in 91% of LMS, 60% of BLM, and 50% of STUMP, but none of usual LM and CLM. More than 10% of cells positive for Ki-67 were observed in 83% of LMS, 100% of STUMP, and 48% of BLM, but none of usual LM and CLM. Our study indicates that distinct expression patterns for p16, p53, and Ki-67 exist between leiomyosarcoma and usual LM and CLM (P<0.0001). Immunohistochemical study with a panel of antibodies to p16, p53, and Ki-67 is helpful in distinguishing LMS from CLM and usual LM. However, due to significant overlapping staining patterns between LSM and BLM (P=0.09), immunostains for p16, p53, and Ki-67 have limited role in differentiating LMS from BLM.