Abstract Bladder cancer is the tenth most frequently diagnosed cancer globally. Classification of high- or low-grade tumors is based on cytological differentiation and is an important prognostic factor. LncRNAs regulate gene expression and play critical roles in the occurrence and development of cancer, however, there are few reports on their diagnostic value and co-expression levels with genes, which may be useful as specific biomarkers for prognosis and therapy in bladder cancer. Thus, we performed a marker lesion study to investigate whether gene/lncRNA expression in urothelial carcinoma tissues may be useful in differentiating low-grade and high-grade tumors. RT-qPCR was used to evaluate the expression of the JHDM1D gene and the lncRNAs CTD-2132N18.2, SBF2-AS1, RP11-977B10.2, CTD-2510F5.4, and RP11-363E7.4 in 20 histologically diagnosed high-grade and 10 low-grade tumors. A protein-to-protein interaction network between genes associated with JHDM1D gene was constructed using STRING website. The results showed a moderate (positive) correlation between CTD-2510F5.4 and CTD2132N18.2. ROC curve analyses showed that combined JHDM1D and RP11-363E7.4 predicted tumor grade with an AUC of 0.826, showing excellent accuracy. In conclusion, the results indicated that the combined expression of JHDM1D and RP11-363E7.4 may be a prognostic biomarker and a promising target for urothelial tumor therapy. globally high lowgrade low factor however coexpression co Thus genelncRNA lncRNA highgrade RTqPCR RT qPCR JHDMD JHDM D CTD2132N18.2, CTD2132N182 CTDN CTD 2132N18.2, 2132N18 2 N CTD-2132N18.2 SBF2AS1, SBF2AS1 SBFAS SBF2 AS1, AS1 SBF AS SBF2-AS1 RP11977B10.2, RP11977B102 RPB RP11 977B10.2, 977B10 RP B RP11-977B10.2 CTD2510F5.4, CTD2510F54 CTDF 2510F5.4, 2510F5 4 F RP11363E7.4 RP11363E74 RPE 363E7.4 363E7 E RP11-363E7. 1 proteintoprotein protein website positive (positive CTD2510F5.4 2510F5.4 CTD-2510F5. CTD2132N18 CTD2132N18.2 0826 0 826 0.826 accuracy conclusion 2132N182 2132N18.2 2132N1 CTD-2132N18. SBF2AS SBF2-AS RP11977B10 RP11977B10.2 RP1 977B102 977B10.2 977B1 RP11-977B10. CTD2510F5 2510F54 2510F RP11363E7 RP11363E7. 363E74 363E7. 363E RP11-363E7 CTD2510F5. 2510F5. CTD-2510F5 CTD2132N1 CTD2132N18. 082 82 0.82 2132N18. 2132N CTD-2132N18 RP11977B1 RP11977B10. 977B10. 977B RP11-977B10 CTD2510F RP11363E RP11-363E CTD-2510F CTD2132N 08 8 0.8 CTD-2132N1 RP11977B RP11-977B1 0. CTD-2132N RP11-977B

OBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of li patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-β1 was underexpressed 67.0% of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores >7 when compared to patients with Gleason scores <7(p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3% had poor prognostic features. CONCLUSIONS: TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.

Das variáveis anatomopatológicas relacionadas ao prognóstico de enfermos com câncer colorretal, a invasão neural ainda se encontra pouco estudada. OBJETIVO: Verificar se a invasão neural no câncer colorretal estádios B e C de Dukes pode ser considerada como fator prognóstico independente. MÉTODO: Foram estudados 97 doentes operados com intenção curativa e seguidos por período mínimo de cinco anos. Excluíram-se doentes que receberam tratamento adjuvante. Os espécimes cirúrgicos foram corados por hematoxilina-eosina e imunoistoquímica para pesquisa da proteína S-100, com o intuito de se comparar a fidedignidade das técnicas em detectar invasão neural, sendo analisadas comparativamente: acurácia, especificidade, sensibilidade e valores preditivos positivo e negativo. A comparação entre a incidência de invasão neural com relação à recidiva foi realizada, empregando-se o teste do qui-quadrado. A sobrevida e sobrevida livre de doença foram estudadas por análise univariada,. Estabeleceu-se nível de significância de 5% (p £ 0,05) para todos os testes adotados. RESULTADOS: A técnica da HE apresentou fraca habilidade em detectar a invasão neural, não sendo adequada para esta análise em doentes portadores de câncer colorretal. As curvas de sobrevida e sobrevida livre de doença dos enfermos portadores de invasão neural, pesquisada por meio da imunocoloração para proteína S-100 são significativamente piores, identificando aquela característica histológica como valor prognóstico independente (p = 0,0003 e p = 0,0002, respectivamente). A ocorrência de recidiva tumoral foi significativamente maior nos doentes que apresentavam invasão neural (p = 0,0010). CONCLUSÃO: Os resultados do presente estudo permitem concluir que, nos doentes portadores de câncer colorretal, a detecção da invasão neural pela pesquisa imunoistoquímica da proteína S-100 demonstrou ser variável independente, acrescentando informações prognósticas adicionais nos doentes classificados nos estádios B, C e C2 das classificações de Dukes e Astler-Coller, respectivamente.

Among the anatomopathological variables related to the prognosis for patients with colorectal cancer, neural invasion remains little studied. OBJECTIVE: To evaluate whether neural invasion in patients with colorectal cancer in Dukes stages B and C could be considered to be an independent prognostic factor, by means of univariate and multivariate analysis. METHODS: Ninety-seven patients who underwent operations with curative intent by the same surgical team were followed up for a minimum period of five years and were studied. Patients who received adjuvant treatment were excluded. The surgical specimens were stained with hematoxylin-eosin (HE) and immunohistochemical techniques for S-100 protein analysis, with the aim of comparing the two techniques for detecting neural invasion. Accuracy, specificity, sensitivity and positive and negative predictive values were analyzed for HE in relation to S-100 protein. Comparison between the incidence of neural invasion and tumor recurrence was made by using the chi-squared test. Survival and disease-free survival were studied by univariate analysis. A significance level of 5% (p £ 0.05) was established for all the tests adopted. RESULTS: The HE technique presented weak ability to detect neural invasion and was inadequate for this analysis in colorectal cancer patients. The survival and disease-free survival curves for patients with neural invasion, investigated by means of immunostaining for S-100 protein, were significantly worse, thus identifying this histological characteristic as having independent prognostic value (p = 0.0003 and p = 0.0002, respectively). There was significantly more tumor recurrence among patients who presented neural invasion (p = 0.0010). CONCLUSION: The results from the present study allow the conclusion that, among colorectal cancer patients, neural invasion was shown to be an independent variable that gave additional prognostic information regarding patients in stages B, C and C2 of the Dukes and Astler-Coller classifications, respectively.

CONTEXTO: Diferenciação sarcomatosa, que representa evolução para malignidade de alto grau, pode ocorrer em todos os tipos histológicos de câncer renal. RELATO DE CASO: Os autores relatam o caso de uma mulher de 66 anos, com uma massa no rim esquerdo que se revelou um carcinoma de células renais. Após 3,5 anos da nefrectomia radical seguida de vacinação com células dendríticas, a paciente desenvolveu uma recorrência sarcomatosa pura no retroperitônio. Os autores especulam que a terapia com vacina de células dendríticas pode ter desempenhado algum papel na diferenciação ou seleção do componente sarcomatoso do tumor primário.

CONTEXT: Sarcomatous differentiation, which represents transformation to high-grade malignancy, can occur in all histogical types of renal malignancy. CASE REPORT: The authors report on the case of a 66-year-old woman with a right renal mass that was shown to be a clear cell carcinoma. She underwent radical nephrectomy and dendritic cell vaccination and, 3.5 years later, she developed retroperitoneal pure sarcomatous recurrence of the tumor. The authors speculate that the vaccination could have played some role in this differentiation or selection of the sarcomatous component of the primary tumor.

OBJETIVO: O bloqueio androgênico neo-adjuvante em câncer da próstata produz involução do volume tumoral sem melhorar a evolução desses pacientes. Uma das explicações para esse fenômeno é a aquisição de comportamento mais agressivo pelas células tumorais remanescentes que, morfologicamente, apresentam aspecto mais indiferenciado após o bloqueio androgênico. Os objetivos do presente estudo foram avaliar a freqüência de desdiferenciação celular após tratamento antiandrogênico e definir se a neoplasia remanescente apresenta sinais de maior agressividade biológica. MÉTODOS: Trinta pacientes portadores de câncer da próstata localmente avançado foram submetidos a tratamento antiandrogênico neo-adjuvante por quatro meses, seguido de prostatectomia radical. Foram comparados os escores de Gleason da biópsia e do espécime cirúrgico. Ademais, mediu-se o índice de proliferação celular, determinado por imunohistoquímica para o PCNA, sendo considerados positivos os testes com reação nuclear intensa. A porcentagem de núcleos positivos, determinada em 500 células, foi confrontada com as diversas categorias do escore de Gleason do espécime cirúrgico. RESULTADOS: Em 11 espécimes cirúrgicos (37%) o escore de Gleason foi igual ou menor que o encontrado na biópsia, enquanto em 19 (63%) o escore cirúrgico foi maior que o da biópsia (p <0,05). A mediana de expressão do PCNA foi, respectivamente, de 4,5%, 10%, 12% e 14% para os escores de Gleason 2-4, 5-6, 7 e 8-10 (p> 0,05). A mediana dos índices de proliferação celular foi de 9% para tumores confinados à glândula ou ao espécime e de 17% para os extraprostáticos (p<0,05). CONCLUSÃO: Piora do escore de Gleason ocorreu em cerca de dois terços dos pacientes submetidos a tratamento hormonal anti-androgênico. Entretanto, os índices de proliferação celular, medidos pelo PCNA, foram iguais para espécimes com diferentes escores de Gleason. É provável que o bloqueio hormonal neo-adjuvante produza uma piora morfológica da neoplasia, sem, contudo, gerar clones celulares mais agressivos.

BACKGROUND: Neoadjuvant androgen deprivation in prostate cancer induces tumor volume regression but does not improve outcome of the patient. A possible explanation for this phenomenon could be an increase of the residual tumor aggressiveness brought about by antiandrogen therapy. The purpose of the present study was to evaluate the frequency of tumor dedifferentiation following androgen blockade in prostate cancer and to determine if the remaining tumor shows signs of increased aggressiveness. METHODS: Thirty patients bearing locally advanced prostate cancer (stages T2c - T3) were submitted to neoadjuvant anti-androgenic therapy during four months followed by radical prostatectomy. Gleason scores from biopsy and surgical specimens were compared. Furthermore, the cell proliferation index was evaluated by immunohistochemistry assay for PCNA, tests with strong nuclear staining were considered positive. The percentage of positive nuclei, counted in 500 cells, was determined in several categories of the Gleason score from surgical specimens. RESULTS: In 11(37%) surgical specimens the Gleason score was equal or lower than that found in the biopsy and in 19 (63%) the total score was higher in the surgical specimens (p<0.05). The median of PCNA expression was 4.5%, 10%, 12% and 14% in Gleason scores 2-4, 5-6,7 and 8-10, respectively (p>0.05). The median of cell proliferation indexes was 9% for glandular or specimen confined tumors and was 17% for extraprostatic tumors (p<0.05). CONCLUSION: The lower Gleason score was found in almost 2/3 of patients submitted to antiandrogen therapy. However, the cell proliferation index measured by PCNA was the same for tumors with lower or higher Gleason scores. It seems that cell dedifferentiation seen after neoadjuvant androgen deprivation represents a mere morphologic phenomenon and not a real increase in tumor aggressiveness.

Muitos dos oncogenes detectados em neoplasias malignas humanas pertencem à família do gene ras. Mutações nos códons 12, 13 ou 61 em um dos tres genes ras; H-ras, K-ras e N-ras, convertem esses genes em oncogenes ativos. Ensaios rápidos para detecção dessas mutações pontuais, tais como a reação em cadeia de polimertização têm sido desenvolvidos nas últimas décadas e usados para investigar o papel dos genes ras mutados na patogênese de tumores humanos. As mutações no gene ras podem ser encontradas numa variedade de tipos de tumores. Incidências mais altas aparecem em adenocarcinomas do pâncreas (90%) e cólon (50%). Analisamos 11 amostras de tumores primários de pâncreas com diferentes metástases, três amostras de cistadenoma mucinoso e dois casos de ausência de tumor de material incluído em parafina, de onde extraímos o DNA para realização das amplificações. Os resultados mostraram que todos os casos de tumores apresentaram a banda de 135 pares de bases correspondente ao gene mutado e para os normais, a banda característica de 106 pares de bases. Nos três casos de cistadenoma mucinosos, não detectamos a banda de 135 pares de bases , apenas a banda de 106 pares de bases.

Mutations at codons 12, 13, or 61 of the H-ras, K-ras, and N-ras have been detected in human neoplasias by a variety of techniques. Some of these techniques are very sensitive and can detect K-ras mutation in 90% of the cases of pancreatic adenocarcinomas. We analyzed 11 samples of pancreatic adenocarcinoma, three samples of pancreatic mucinous cystadenoma, and two samples without tumors in formalin-fixed paraffin embedded tissue sections. K-ras mutations at codon 12 were detected by a two-step PCR-enriched technique in all the samples of pancreatic adenocarcinoma, but not in cystadenoma or control samples. This technique may be useful for early detection of pancreatic cancer.