Let-7 miRNA's Expression Profile and Its Potential Prognostic Role in Uterine Leiomyosarcoma.

The lethal-7 (let-7) family is an important microRNA (miRNA) group that usually exerts functions as a tumor suppressor. We aimed to evaluate the expression profile of let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, and let-7i and to assess their value as prognostic markers in uterine leiomyosarcoma (LMS) patients. The miRNAs expression profile was assessed in 34 LMS and 13 normal myometrium (MM) paraffin-embedded samples. All let-7 family members showed downregulation in LMS. Our findings showed that patients with let-7e downregulation had worse overall survival (OS) and is an independent prognostic factor (hazard ratio [HR] = 2.24). In addition, almost half the patients had distant metastasis. LMS patients with downregulated let-7b and let-7d had worse disease-free survival (DFS); they are not independent prognostic factors (HR = 2.65). Patients' ages were associated with let-7d, let-7e and let-7f (p = 0.0160) downregulation. In conclusion, all the let-7 family members were downregulated in LMS patients, and the greater the loss of expression of these molecules, the greater their relationship with worse prognosis of patients. Let-7e expression might influence the OS, while let-7b and le-7d might influence the DFS. The lowest expression levels of let-7d, let-7e, and let-7f were associated with the oldest patients. Our findings indicate strong evidence of let-7's role as a potential prognostic biomarker in LMS.

External validation of nomogram to predict inguinal lymph node metastasis in patients with penile cancer and clinically negative lymph nodes

ABSTRACT Introduction Penile cancer (PC) occurs less frequently in Europe and in the United States than in South America and parts of Africa. Lymph node (LN) involvement is the most important prognostic factor, and inguinal LN (ILN) dissection can be curative; however, ILN dissection has high morbidity. A nomogram was previously developed based on clinicopathological features of PC to predict ILN metastases. Our objective was to conduct an external validation of the previously developed nomogram based on our population. Materials and methods We included men with cN0 ILNs who underwent ILN dissection for penile carcinoma between 2000 and 2014. We performed external validation of the nomogram considering three different external validation methods: k-fold, leave-one-out, and bootstrap. We also analyzed prognostic variables. Performance was quantified in terms of calibration and discrimination (receiver operator characteristic curve). A logistic regression model for positive ILNs was developed based on clinicopathological features of PC. Results We analyzed 65 men who underwent ILN dissection (cN0). The mean age was 56.8 years. Of 65 men, 24 (36.9%) presented with positive LNs. A median 21 ILNs were removed. Considering the three different methods used, we concluded that the previously developed nomogram was not suitable for our sample. Conclusions In our study, the previously developed nomogram that was applied to our population had low accuracy and low precision for correctly identifying patients with PC who have positive ILNs.

Urological cancer related to familial syndromes

ABSTRACT Cancer related to hereditary syndromes corresponds to approximately 5-10% of all tumors. Among those from the genitourinary system, many tumors had been identified to be related to genetic syndromes in the last years with the advent of new molecular genetic tests. New entities were described or better characterized, especially in kidney cancer such as hereditary leiomyomatosis renal cell carcinoma (HLRCC), succinate dehydrogenase kidney cancer (SDH-RCC), and more recently BAP1 germline mutation related RCC. Among tumors from the bladder or renal pelvis, some studies had reinforced the role of germline mutations in mismatch repair (MMR) genes, especially in young patients. In prostate adenocarcinoma, besides mutations in BRCA1 and BRCA2 genes that are known to increase the incidence of high-risk cancer in young patients, new studies have shown mutation in other gene such as HOXB13 and also polymorphisms in MYC, MSMB, KLK2 and KLK3 that can be related to hereditary prostate cancer. Finally, tumors from testis that showed an increased in 8 - 10-fold in siblings and 4 - 6-fold in sons of germ cell tumors (TGCT) patients, have been related to alteration in X chromosome. Also genome wide association studies GWAS pointed new genes that can also be related to increase of this susceptibility.

Epidermal growth factor receptor as an adverse survival predictor in squamous cell carcinoma of the penis.

Penile carcinoma (PC) is more frequent in underdeveloped countries, generally is diagnosed at an advanced stage when therapeutic options are restricted, and thus is associated with high morbidity/mortality rates. Recent studies have demonstrated clinical benefits with epidermal growth factor receptor (EGFR)-targeted therapy in patients with PC, although there is no test that provides accurate patient selection. The aim of the present study was to evaluate the prognostic value of EGFR gene and protein status in tumor samples from patients with primary penile squamous cell carcinoma. We assessed the expression of wild-type and 2 mutant EGFR isoforms (delA746-E750 and mL858R) by immunohistochemistry in 139 samples, of which 49 were also evaluated for EGFR copy number by fluorescence in situ hybridization (FISH). Positive immunohistochemical staining of wild-type and mutant EGFR was evidenced by complete and strong membranous staining. For FISH analysis, cases were considered unaltered, polysomic, or amplified, as determined by signals of the EGFR gene and chromosome 7. An independent cohort of 107 PC samples was evaluated for mutations in EGFR, KRAS, and BRAF. Protein overexpression was noted in nearly half of the cases and was associated with cancer recurrence (P=.004) and perineural invasion (P=.005). Expression of the 2 mutated EGFR isoforms was not observed. The FISH status was not associated with protein expression. Altered FISH (polysomy and gene amplification) was an independent risk factor for dying of cancer. Only 1 patient of 107 presented KRAS mutations, and no mutations of EGFR or BRAF were observed.

Urological cancer related to familial syndromes.

Cancer related to hereditary syndromes corresponds to approximately 5-10% of all tumors. Among those from the genitourinary system, many tumors had been identified to be related to genetic syndromes in the last years with the advent of new molecular genetic tests. New entities were described or better characterized, especially in kidney cancer such as hereditary leiomyomatosis renal cell carcinoma (HLRCC), succinate dehydrogenase kidney cancer (SDH-RCC), and more recently BAP1 germline mutation related RCC. Among tumors from the bladder or renal pelvis, some studies had reinforced the role of germline mutations in mismatch repair (MMR) genes, especially in young patients. In prostate adenocarcinoma, besides mutations in BRCA1 and BRCA2 genes that are known to increase the incidence of high-risk cancer in young patients, new studies have shown mutation in other gene such as HOXB13 and also polymorphisms in MYC, MSMB, KLK2 and KLK3 that can be related to hereditary prostate cancer. Finally, tumors from testis that showed an increased in 8 - 10-fold in siblings and 4 - 6-fold in sons of germ cell tumors (TGCT) patients, have been related to alteration in X chromosome. Also genome wide association studies GWAS pointed new genes that can also be related to increase of this susceptibility.

A genomic case study of desmoplastic small round cell tumor: comprehensive analysis reveals insights into potential therapeutic targets and development of a monitoring tool for a rare and aggressive disease.

BACKGROUND: Genome-wide profiling of rare tumors is crucial for improvement of diagnosis, treatment, and, consequently, achieving better outcomes. Desmoplastic small round cell tumor (DSRCT) is a rare type of sarcoma arising from mesenchymal cells of abdominal peritoneum that usually develops in male adolescents and young adults. A specific translocation, t(11;22)(p13;q12), resulting in EWS and WT1 gene fusion is the only recurrent molecular hallmark and no other genetic factor has been associated to this aggressive tumor. Here, we present a comprehensive genomic profiling of one DSRCT affecting a 26-year-old male, who achieved an excellent outcome. METHODS: We investigated somatic and germline variants through whole-exome sequencing using a family based approach and, by array CGH, we explored the occurrence of genomic imbalances. Additionally, we performed mate-paired whole-genome sequencing for defining the specific breakpoint of the EWS-WT1 translocation, allowing us to develop a personalized tumor marker for monitoring the patient by liquid biopsy. RESULTS: We identified genetic variants leading to protein alterations including 12 somatic and 14 germline events (11 germline compound heterozygous mutations and 3 rare homozygous polymorphisms) affecting genes predominantly involved in mesenchymal cell differentiation pathways. Regarding copy number alterations (CNA) few events were detected, mainly restricted to gains in chromosomes 5 and 18 and losses at 11p, 13q, and 22q. The deletions at 11p and 22q indicated the presence of the classic translocation, t(11;22)(p13;q12). In addition, the mapping of the specific genomic breakpoint of the EWS-WT1 gene fusion allowed the design of a personalized biomarker for assessing circulating tumor DNA (ctDNA) in plasma during patient follow-up. This biomarker has been used in four post-treatment blood samples, 3 years after surgery, and no trace of EWS-WT1 gene fusion was detected, in accordance with imaging tests showing no evidence of disease and with the good general health status of the patient. CONCLUSIONS: Overall, our findings revealed genes with potential to be associated with risk assessment and tumorigenesis of this rare type of sarcoma. Additionally, we established a liquid biopsy approach for monitoring patient follow-up based on genomic information that can be similarly adopted for patients diagnosed with a rare tumor.

Radical prostatectomy and positive surgical margins: relationship with prostate cancer outcome

Introduction Positive surgical margins (PSMs) are an adverse factor that may predict a worse outcome in patients submitted to radical prostatectomy (RP). However, not all of these cases will evolve to biochemical (BCR) or clinical (CR) recurrence, therefore relationship between PSMs and these recurrent events has to be correlated with other clinical and pathologic findings to indicate complementary treatment for selected patients. Materials and Methods Of 1250 patients submitted to open retropubic radical prostatectomy (RRP), between March 1991 and June 2008, the outcome of 161 patients with PSMs and of 67 without PSMs as a control group, comprising a total of 228 cases were retrospectively reviewed. A minimum follow-up time of 2 years after surgery was considered. BCR was determined when PSA ≥ 0.2ng/mL. CR was determined whenever there was clinical evidence of tumor. Chi-square test was used to correlate clinical and pathologic variables with PSMs. Time interval to biochemical recurrence was analyzed by the Kaplan-Meier product limit analysis using the log-rank test for comparison between groups. Univariate and multivariate Cox stepwise logistic regression models were used to identify significant predictors of risk of shorter intervals to BCR. Results Prostate circumference margin was the most common site with 78 cases (48.44%). Regarding the outcome of 228 cases from both groups, BCR occurred in 68 patients (29.82%), and CR in 10 (4.38%). Univariate analysis showed statistically significant associations (p < 0.001) between presence of PSMs with BCR, but not with CR (p = 0.05). At follow-up of the 161 patients with PSMs, only 61(37.8%) presented BCR, while 100 (62.8%) did not. BCR correlated with pathologic stage; Gleason score; preoperative PSA; tumor volume in the specimen; capsular and perineural invasion; presence and number of PSMs. CR correlated only with angiolymphatic invasion and Gleason score. Considering univariate ...

Bannayan-Riley-Ruvalcaba syndrome with deforming lipomatous hamartomas in infant - Case report / Sindrome de Bannayan-Riley-Ruvalcaba com hamartomas lipomatosos deformantes em lactente - Relato de caso

Bannayan-Riley-Ruvalcaba Syndrome is a rare condition caused by mutations in the PTEN gene. It displays association of multiple lipomas, macrocephaly, hemangiomas, hamartomatous intestinal polyposis, developmental delay and speckled pigmented maculae on the male genitalia. We report the case of a nine-month-old boy who had fast growing and progressive tumors for three months, macrocephaly and lentigines on the penis. Imaging tests showed extensive lipomatosis with invasion of paraspinal muscles, enlargement of the spinal canal and spinal cord compression; after surgical excision of the mass, the pathology was consistent with lipoma. Adipocyte culture karyotype demonstrated PTEN mutation. We present this case for its rarity and exuberance.

A síndrome de Bannayan-Riley-Ruvalcaba é afecção rara, causada por mutações no gene PTEN. Apresenta associação de múltiplos lipomas, macrocefalia, hemangiomas, polipose hamartomatosa intestinal, atraso do desenvolvimento e máculas salpicadas na genitália masculina. Relatamos o caso de um menino de nove meses com lesões tumorais de crescimento rápido e progressivo em três meses de evolução, macrocefalia e lentigos no pênis. Exames de imagem demonstraram extensa lipomatose com invasão da musculatura paraespinhal, alargamento do canal vertebral e compressão medular. Depois da excisão cirúrgica da massa, o anatomopatológico foi compatível com lipoma. A análise do cariótipo em cultura de adipócitos demonstrou mutação do PTEN. Apresentamos este caso por sua exuberância e raridade.

Comment on: EGFR mutational status in Brazilian patients with penile carcinoma.

The authors describe the results on EGFR molecular alterations of 29 Brazilian patients with penile carcinoma (PC). DNA extracted from frozen tumor tissue of all patients was submitted to direct sequencing of the four exons (18 - 21) responsible for the EGFR tyrosine-kinase activity. Corroborating the data by Di Lorenzo et al. published in Expert Opin Ther Targets, none of the sequenced tumor samples showed relevant alterations in the four studied exons of the EGFR gene.

Immunoexpression of cell cycle biomarkers in neuroblastoma samples and its correlation with prognostic factors / Imunoexpressão de biomarcadores do ciclo celular em amostras de neuroblastomas e sua relação com fatores prognósticos

INTRODUCTION: It is widely known that the expression levels of molecules involved in apoptosis regulation and cell proliferation have prognostic value in patients with neuroblastomas. OBJECTIVE: To determine the expression of Ki67, B-cell lymphoma 2 (BCL-2), phosphatase and tensin homolog (PTEN), BCL-2 associated protein X (BAX) and caspase-8 proteins in neuroblastomas and to propose new prognostic biomarkers that could enable a better classification of risk groups. MATERIAL AND METHODS: Formalin fixed paraffin embedded neuroblastoma samples (n = 23) were arranged into tissue microarray blocks and analyzed by immunohistochemistry. The patients were classified according to clinical and pathological prognostic factors (age, site, presence or absence of bone-marrow infiltration, poorly or well differentiated ganglioneuroblastoma, Schwannian stroma rich or poor, favorable or unfavorable Shimada histology, and presence or absence of MYCN oncogene amplification) and clinical course (with or without fatal outcome, with or without relapses/residual lesion). RESULTS: Twelve patients were female; nine children were over 18 months old; nine had extra-abdominal tumors; nine had tumors with unfavorable histology. Fifteen patients underwent bone-marrow biopsy and four were positive for metastasis. Nine patients progressed to fatal outcome. CONCLUSION: Ki67 immunoexpression was lower in cases of Schwannian-stroma rich neuroblastomas (p = 0.018) and higher in poorly differentiated cases (p = 0.013). PTEN was less positive in stroma rich neuroblastomas (p = 0.024). Caspase-8 was more immunopositive in cases of negative bone marrow infiltration (p = 0.035). Therefore, these biomarkers could be applied to discriminate groups with poor prognosis.

INTRODUÇÃO: Sabe-se que os níveis de expressão de moléculas envolvidas na regulação da apoptose e da proliferação celular apresentam valor prognóstico em pacientes com neuroblastomas. OBJETIVO: Avaliar a imunoexpressão das proteínas Ki67, B-cell lymphoma 2 (BCL-2), phosphatase and tensin homolog (PTEN), caspase-8 e BCL-2 associated protein X (BAX) em neuroblastomas na tentativa de propor novos biomarcadores prognósticos que poderiam auxiliar na melhor discriminação dos grupos de risco. MATERIAL E MÉTODOS: Amostras de neuroblastoma (n = 23) foram submetidas à técnica tissue microarray e analisadas com imuno-histoquímica. Os pacientes foram classificados de acordo com os fatores prognósticos clínico-patológicos (idade, localização, medula óssea infiltrada ou não, pouco diferenciado ou em diferenciação/ganglioneuroblastoma, rico ou pobre em estroma com células de Schwann, histologia favorável ou desfavorável segundo Shimada, presença ou não da amplificação do MYCN) e com o curso clínico (se em óbito ou vivo, com ou sem lesão residual/recidiva). RESULTADOS: Doze casos eram do sexo feminino; nove tinham idade acima de 18 meses; nove apresentavam tumores extra-abdominais; e nove cursavam com histologia desfavorável. Quinze pacientes foram submetidos à biópsia de medula óssea, sendo quatro com apresentação de metástase. Nove pacientes evoluíram ao óbito. CONCLUSÃO: A imunoexpressão do Ki67 foi mais baixa nos casos ricos em estroma (p = 0,018) e elevada nos casos pouco diferenciados (p = 0,013). O PTEN apresentou-se menos positivo em neuroblastomas ricos em estroma (p = 0,024). A caspase-8 foi mais imunopositiva em casos com medula óssea negativa (p = 0,035). Esses biomarcadores poderiam ser utilizados para auxiliar a discriminar grupos de pacientes de pior prognóstico.

Bannayan-Riley-Ruvalcaba syndrome with deforming lipomatous hamartomas in infant--case report.

Bannayan-Riley-Ruvalcaba Syndrome is a rare condition caused by mutations in the PTEN gene. It displays association of multiple lipomas, macrocephaly, hemangiomas, hamartomatous intestinal polyposis, developmental delay and speckled pigmented maculae on the male genitalia. We report the case of a nine-month-old boy who had fast growing and progressive tumors for three months, macrocephaly and lentigines on the penis. Imaging tests showed extensive lipomatosis with invasion of paraspinal muscles, enlargement of the spinal canal and spinal cord compression; after surgical excision of the mass, the pathology was consistent with lipoma. Adipocyte culture karyotype demonstrated PTEN mutation. We present this case for its rarity and exuberance.

Biópsia percutânea por agulha grossa de tumores de partes moles guiada por tomografia computadorizada: resultados e correlação com análise da peça cirúrgica / Percutaneous computed tomography-guided core needle biopsy of soft tissue tumors: results and correlation with surgical specimen analysis

OBJETIVO: Avaliar a eficácia da biópsia percutânea por agulha grossa (BPAG) de tumores de partes moles guiada por tomografia computadorizada (TC), em relação ao sucesso na obtenção de amostra para análise, e comparar o diagnóstico da BPAG com o resultado anatomopatológico da peça cirúrgica, quando disponível. MATERIAIS E MÉTODOS: Foram revisados os prontuários e laudos diagnósticos de 262 pacientes com tumores de partes moles submetidos a BPAG guiada por TC em um centro de referência oncológico entre 2003 e 2009. RESULTADOS: Das 262 biópsias realizadas, foi possível a obtenção de amostra adequada em 215 (82,1%). Os tumores mais prevalentes foram os sarcomas (38,6%), carcinomas metastáticos (28,8%), tumores mesenquimais benignos (20,5%) e linfomas (9,3%). Foi possível realizar graduação histológica em 92,8% dos pacientes com sarcoma, sendo a maioria (77,9%) classificada como alto grau. Do total de pacientes, 116 (44,3%) realizaram cirurgia para exérese e confirmação diagnóstica. A BPAG mostrou acurácia de 94,6% na identificação de sarcomas, com sensibilidade de 96,4% e especificidade de 89,5%. A graduação histológica teve concordância significativa entre a BPAG e a peça cirúrgica (p < 0,001; kappa = 0,75). CONCLUSÃO: A BPAG guiada por TC demonstrou elevada acurácia diagnóstica na avaliação de tumores de partes moles e na graduação histológica dos sarcomas, permitindo um adequado planejamento terapêutico.

OBJECTIVE: To evaluate the efficacy of percutaneous computed tomography (CT)-guided core needle biopsy of soft-tissue tumors in obtaining appropriate samples for histological analysis, and compare its diagnosis with the results of the surgical pathology as available. MATERIALS AND METHODS: The authors reviewed medical records, imaging and histological reports of 262 patients with soft-tissue tumors submitted to CT-guided core needle biopsy in an oncologic reference center between 2003 and 2009. RESULTS: Appropriate samples were obtained in 215 (82.1%) out of the 262 patients. The most prevalent tumors were sarcomas (38.6%), metastatic carcinomas (28.8%), benign mesenchymal tumors (20.5%) and lymphomas (9.3%). Histological grading was feasible in 92.8% of sarcoma patients, with the majority of them (77.9%) being classified as high grade tumors. Out of the total sample, 116 patients (44.3%) underwent surgical excision and diagnosis confirmation. Core biopsy demonstrated 94.6% accuracy in the identification of sarcomas, with 96.4% sensitivity and 89.5% specificity. A significant intermethod agreement about histological grading was observed between core biopsy and surgical resection (p < 0.001; kappa = 0.75). CONCLUSION: CT-guided core needle biopsy demonstrated a high diagnostic accuracy in the evaluation of soft tissue tumors as well as in the histological grading of sarcomas, allowing an appropriate therapeutic planning.

Immunohistochemical expression of CD44s in renal cell carcinoma lacks independent prognostic significance.

PURPOSE: To analyze the immunohistochemical expression of the standard isoform of CD44 (CD44s) adhesion molecule in clear cell renal cell carcinoma (CCRCC) and its impact on clinical outcomes. MATERIALS AND METHODS: Ninety-nine consecutive patients treated surgically for RCC between 1992 and 2009 were selected. A single pathologist reviewed all cases to effect a uniform reclassification and determine the most representative tumor areas for construction of a tissue microarray. The same pathologist, who was blinded to the outcome of the cases, semi-quantitatively scored the staining intensity of CD44s in all specimens. The counting was done using the H-Score algorithm. RESULTS: Of the 99 immunostained RCC specimens, 57(57.7 %) showed low expression, and 42(42.4 %) showed high expression levels of CD44s. The expression of CD44s was directly associated with tumor size (p = 0.03), clinical stage (p = 0.02) and Fuhrman grade (p = 0.02). Disease specifi c survival (DSS) rates for patients whose specimens expressed low and high levels of CD44s was 88.1 % and 67.5 %, respectively (p = 0.009). Progression free survival (PFS) rates in patients with low and high expression of CD44s were 78.8 % and 61.7 %, respectively (p = 0.05). Classical features such as the presence of metastasis and clinical stage remained isolated predictors of survival. CONCLUSIONS: Immunohistochemical expression of CD44s was associated with important clinical variables such as stage and Fuhrman grade. However, it was not an independent predictor of survival. Therefore, we believe it has a limited role as a prognostic marker in patients with CCRCC.

Immunohistochemical expression of CD44s in renal cell carcinoma lacks independent prognostic significance

PURPOSE: To analyze the immunohistochemical expression of the standard isoform of CD44 (CD44s) adhesion molecule in clear cell renal cell carcinoma (CCRCC) and its impact on clinical outcomes. MATERIALS AND METHODS: Ninety-nine consecutive patients treated surgically for RCC between 1992 and 2009 were selected. A single pathologist reviewed all cases to effect a uniform reclassification and determine the most representative tumor areas for construction of a tissue microarray. The same pathologist, who was blinded to the outcome of the cases, semi-quantitatively scored the staining intensity of CD44s in all specimens. The counting was done using the H-Score algorithm. RESULTS: Of the 99 immunostained RCC specimens, 57(57.7%) showed low expression, and 42(42.4%) showed high expression levels of CD44s. The expression of CD44s was directly associated with tumor size (p = 0.03), clinical stage (p = 0.02) and Fuhrman grade (p = 0.02). Disease specific survival (DSS) rates for patients whose specimens expressed low and high levels of CD44s was 88.1% and 67.5%, respectively (p = 0.009). Progression free survival (PFS) rates in patients with low and high expression of CD44s were 78.8% and 61.7%, respectively (p = 0.05). Classical features such as the presence of metastasis and clinical stage remained isolated predictors of survival. CONCLUSIONS: Immunohistochemical expression of CD44s was associated with important clinical variables such as stage and Fuhrman grade. However, it was not an independent predictor of survival. Therefore, we believe it has a limited role as a prognostic marker in patients with CCRCC.

CD133 immunohistochemical expression predicts progression and cancer-related death in renal cell carcinoma.

PURPOSE: To evaluate the prognostic impact of the histological expression of CD133 in renal cell carcinoma (RCC). METHODS: From 1992 to 2009, 142 consecutive patients underwent radical nephrectomy or partial nephrectomy for RCC. All cases were reviewed by a single pathologist and then subjected to analysis of the immunohistochemical expression of CD133 using tissue microarray. Several clinical and pathological variables were also evaluated. RESULTS: The median postoperative follow-up was 44 months. Of the 142 immunostained RCC specimens, 77 (54%) showed low and 65 (46%) high expression of CD133. Expression of CD133 was associated with clinical stage (P = 0.05), lymph node involvement (P = 0.03), metastatic disease (P = 0.02) and MVI (P = 0.03). Among other variables, clinical stage, necrosis and metastasis were associated with disease-specific survival (DSS) and progression-free survival (PFS) on univariate analysis. The 5-year PFS rates in patients who provided specimens with high and low expression of CD133 were 83 and 66%, respectively (P = 0.01). It was observed that the 5-year DSS for patients who provided specimens with high and low expression of CD133 was 90 and 71%, respectively (P = 0.003). Multivariate survival analysis showed that patients in the CD133 low-expression group had a higher probability of disease progression (HR 3.4, P = 0.02) and a higher probability of death from cancer (HR 2.4, P = 0.01). CONCLUSIONS: Immunohistochemical expression of CD133 had an impact on survival in patients with RCC, which shows that CD133 might be a useful tool for risk stratification. Low expression of this marker remained as an independent predictor of poor DSS and PFS.

Tumor fibroso solitário na pele: relato de caso / Solitary fibrous tumor of the skin: case report

O tumor fibroso solitário (TFS) é uma neoplasia benigna muito rara, derivada de células mesenquimais. Há relatos de casos deste tumor em diversos sítios pleurais ou extrapleurais, sendo a região cutânea e subcutânea localizações ainda mais incomuns. O prognóstico, na maioria dos casos, é bom, mas o comportamento pode ser agressivo. O diagnóstico clínico diferencial é importante na prática diária do cirurgião plástico, pois não raramente aparecem lesões tumorais dos componentes do revestimento cutâneo, com características semelhantes ao TFS - consistência fibro elástica e não aderência a planos profundos - que devem ser bem conhecidas e diferenciadas de neoplasias malignas, para que o tratamento adequado seja instituído.

Solitary fibrous tumor (TFS) is a very rare benign tumor, derived from mesenchymal cells. There are reports of cases of this tumor in different pleural or extra-pleural’s sites, and the skin is even a more unusual spot. The prognosis in most cases is good, but the behavior in few cases can be aggressive. The differential diagnosis is important in the daily practice of plastic surgeons. There are several lesions well known with similar characteristics to TFS in skin layers: fibro elastic consistency, not adhered to deep planes. Those lesions should be differentiated from malignant neoplasms, so that proper treatment is instituted.

Análise de genes diferencialmente expressos em neoplasias de origem mesenquimal avançado / Expression profile of mesenchymal tumors

Os tumores mesenquimais são neoplasias raras, de alta morbidade e mortalidade dependendo do subtipo histológico. Os eventos moleculares relacionados aos seus comportamentos como agressividade local e metástase permanecem desconhecidos. Neste estudo nós comparamos o perfil da expressão gênica de 102 amostras de tumores mesenquimais de diversos tipos histológicos e comportamentos biológicos através de cDNA microarray. Nós identificamos um grupo de seis genes relacionados funcionalmente à agressividade local (SNRPD3, MEGF9, SPTAN-1, AFAP1L2, ENDOD1 e SERPIN5), e outro grupo de seis genes relacionados à potencial metastático (ZWINTAS, TOP2A, UBE2C, ABCF1, MCM2 e ARL6IP5). Além disto, o reconhecimento de assinaturas moleculares trouxe melhor entendimento da patogênese destas neoplasias. Através de análise não supervisionada, o perfil de expressão gênica global dos casos analisados, foi capaz de diferenciar três grandes grupos de tumores de partes moles: fibromatoses (FM), sarcomas sinoviais (SS) e os demais tipos. Na procura de classificadores pelo discriminador linear de Fisher, encontramos 3 trios de genes capazes de separar os sarcomas sinoviais com 100% de acerto dos outros subtipos tumorais e 92 pares de genes capazes de separar as fibromatoses dos fibrossarcomas com 100% de acerto. Em outra abordagem avaliamos através das técnicas de cDNA microarray, Q-PCR e imunoistoquímica, a expressão de GFAP em diversos tipos histológicos de tumores mesenquimais. Os achados encontrados nos mostraram que a expressão de GFAP é decorrente da capacidade de diferenciação cartilaginosa presente em alguns sarcomas.

O arranjo em matriz de amostras teciduais (tissue microarray): larga escala e baixo custo ao alcance do patologista / Tissue microarrays: high throughput and low cost avaiable for pathologists

O arranjo em matriz de amostras teciduais, ou tissue microarray (TMA), é uma técnica descrita em 1998 por Kononen et al. com ampla aceitação pela literatura mundial. Com um conceito extremamente simples, trata-se de agrupar um grande número de amostras teciduais em um único bloco de parafina, permitindo o estudo de expressão de marcadores moleculares em larga escala com grande aproveitamento do material arquivado, do tempo e dos custos. Discutimos as vantagens e limitações do método, as estratégias e técnica de construção, as aplicações e dificuldades encontradas para a patologia investigativa nos últimos cinco anos de uso no Hospital do Câncer A. C. Camargo.

Tissue microarrays (TMA) is a worldwide well accepted technique described in 1998 by Kononen et al. It uses an extremely simple concept of ordering hundreds of samples in just one paraffin block to evaluate protein expression in large cohorts with great advantages on costs, time and sample saving. We discuss the technique, its advantages and limitations, strategies to construct the receptor block, its usefulness and difficulties experienced in the last five years at Hospital do Cancer A.C. Camargo.