Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively

Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during diagnosis and the development of effective clinical parameters is crucial for correct management of the disease. The use of biological markers in cancer is a useful tool to determine patient prognosis. Ki--67 is a protein marker for proliferation of somatic cells and is widely used in prognostic studies of various types of tumor, including STSs. Cluster of differentiation 100 (CD100) is a member of the semaphorin family. The family was initially described as axon guidance molecules important for angiogenesis, organogenesis, apoptosis and neoplasia. CD100 was previously utilized as a prognostic factor in tumors and also in STSs. In the present study, protein expression of Ki--67 and CD100 was analyzed by immunohistochemistry in samples of STS patients of the Barretos Cancer Hospital (Barretos, Brazil) to establish prognostic criteria of the disease. Results demonstrate a correlation between CD100 expression and poor prognosis, consistent with a previous study. Moreover, the expression of Ki-67 was identified to correlate with presence of local or locoregional recurrence. To the best of our knowledge, no large casuistic study has revealed this correlation between Ki--67 and local recurrence in STSs. The use of Ki--67 and CD100 as markers in clinical pathological analysis may be suitable as a prognostic criterion in disease progression.

Algunos elementos para el diagnostico y prognosis de la dinamica demografica del Ecuador

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TWIST1 Is a Molecular Marker for a Poor Prognosis in Oral Cancer and Represents a Potential Therapeutic Target

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence Analysis of Cleft Type and Supernumerary Teeth Eruption in the Prognosis of Bone Graft in Patients With Cleft Palate

Objective: The aim of this study was to investigate the influence of cleft type and supernumerary tooth eruption on the treatment of palatal clefts with alveolar bone grafts.Materials and Methods: In this article, medical records of 40 patients with palatal clefts and associated supernumerary teeth who were treated with alveolar bone grafting in the Hospital for Craniofacial Anomalies Rehabilitation were assessed. The patients were studied to assess the influence of supernumerary teeth and the cleft severity on the prognosis of the alveolar bone graft.Results: Forty medical records were included in the assessment. When the teeth in the cleft had an anatomic shape close to canine, we called them precanine. When they were very small or malformed, we called them anomalous lateral incisors. The teeth studied showed good prognoses and were more expressive in the preforaminal clefts (87.5%) than in the transforaminal ones (62.5%). Moreover, the transforaminal clefts presented a higher percentage in satisfactory and poor prognoses (37.5%). The authors found that supernumerary teeth influenced the maintenance of alveolar bone graft height and that transforaminal clefts presented a worse prognosis than preforaminal clefts.

Genomic profiling of human penile carcinoma predicts worse prognosis and survival

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Minimal residual disease in cerebrospinal fluid at diagnosis: a more intensive treatment protocol was able to eliminate the adverse prognosis in children with acute lymphoblastic leukemia

We analyzed cerebrospinal fluid (CSF) samples from 65 consecutive children with acute lymphoblastic leukemia (ALL) treated according to two different treatment protocols (GBTLI-ALL-93 and -99) with no puncture accident for minimal residual disease (MRD) in the central nervous system (CNS). Minimal residual disease was detected by polymerase chain reaction (PCR) with homo/heteroduplex analysis using consensus primers to IgH and TCR genes. MRD in the CSF at diagnosis was detected by PCR in 46.8% of children with no puncture accident or morphological involvement. In patients treated with GBTLI-ALL-93 a significantly lower 5-year event-free survival (EFS) was demonstrated for those with CSF involvement, in univariate (p = 0.01) and multivariate (p = 0.04) analysis. This observation was not true for patients treated with the more intensive protocol GBTLI-ALL-99 (p = 0.81). These findings suggest that MRD detection in the CSF is a common event in children with ALL. Treatment intensification provided by the GBTLI-ALL-99 apparently overcomes the detrimental effect of CNS minimal residual disease at diagnosis.

PIK3CA exon 20 mutations are associated with poor prognosis in breast cancer patients

OBJECTIVES: The phosphatidylinositol 3-kinase/AKT axis is an important cell-signaling pathway that mediates cell proliferation and survival, two biological processes that regulate malignant cell growth. The phosphatidylinositol 3-kinase CA gene encodes the p110 alpha subunit of the phosphatidylinositol 3-kinase protein. There are phosphatidylinositol 3-kinase CA mutations in several types of human tumors, and they are frequently observed in breast cancer. However, these mutations have not been investigated in Brazilian breast cancer patients. METHODS: PCR-SSCP and direct DNA sequencing were performed to identify phosphatidylinositol 3-kinaseCA exon 9 and exon 20 mutations in 86 patients with sporadic breast cancer. The relationships between PIK3CA mutations and patient clinicopathological characteristics and survival were analyzed. The presence of the TP53 mutation was also examined. RESULTS: Twenty-three (27%) of the 86 primary breast tumors contained PIK3CA mutations. In exons 9 and 20, we identified the hotspot mutations E542K, E545K, and H1047R, and we identified two new missense mutations (I1022V and L1028S) and one nonsense (R992X) mutation. Phosphatidylinositol 3-kinase CA exon 20 mutations were associated with poor overall survival and TP53 gene mutations. CONCLUSIONS: Phosphatidylinositol 3-kinase CA mutations are common in tumors in Brazilian breast cancer patients, and phosphatidylinositol 3-kinase CA and TP53 mutations are not mutually exclusive. Phosphatidylinositol 3-kinase CA exon 20 mutations are associated with poor survival, and they may be useful biomarkers for identifying breast cancer patients with aggressive tumors and for predicting the response to treatment with PI3K pathway inhibitors.

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

Background: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). Methods: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). Conclusion: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

Immune expression of E-cadherin and alpha, beta and gamma-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

Introduction: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and alpha-, beta- and gamma-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. Materials and Methods: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. Results: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of a-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). Conclusions: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of a-catenin expression is related to tumor size in upper tract urothelial carcinomas.

The Value of Immunohistochemical Expression of BAX in Formulating a Prognosis for Canine Cutaneous Mast Cell Tumours

Irnmunohistochcmical expression of BAX was evaluated in 24 canine cutaneous mast cell tumours in order to verify the relationship of this expression to the histopathological grade of the lesions and its prognostic value for clinical outcome. BAX expression increased with higher histopathological grades (P = 0.0148; P < 0.05 between grades I and III). Animals with high levels of BAX expression were 4.25 times more likely to die from the disease and had shorter post-surgical survival times (P = 0.0009). These results suggest that alterations in BAX expression may be related to the aggressiveness of canine cutaneous mast cell tumours, indicating that immunohistochemical detection of BAX may be predictive of clinical outcome. (C) 2011 Elsevier Ltd. All rights reserved.

Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells of patients with aggressive B-cell non-Hodgkin's lymphoma is not associated with prognosis

The Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B-cell lymphomas (DLBCL) and related its presence to the clinical variables and risk factors. The results show that EBV detection in 21.5% of patients is not associated with age, gender, staging, B symptoms, international prognostic index scores or any analytical parameters, including lactate dehydrogenase (LDH) or beta-2 microglobulin (B2M). The majority of patients were treated with R-CHOP-like (rituximab. cyclophosphamide, doxorubicin, vincristine and prednisolone or an equivalent combination) and some with CHOP-like chemotherapy. Response rates [complete response (CR) + partial response (PR)] were not significantly different between EBV-negative and -positive cases, with 93.2 and 88.9%, respectively. The survival rate was also similar in the two groups, with 5-year overall survival (OS) rates of 64.3 and 76.7%, respectively. However, when analyzing the treatment groups separately there was a trend in EBV-positive patients for a worse prognosis in patients treated with CHOP-like regimens that was not identified in patients treated with R-CHOP-like regimens. We conclude that EBV detection in the bone marrow and blood mononuclear cells of DLBC patients has the same frequency of EBV detection on tumoral lymphoma tissue but is not associated with the risk factors, response rate and survival in patients treated mainly with immunochemotherapy plus rituximab. These results also suggest that the addition of rituximab to chemotherapy improves the prognosis associated with EBV detection in DLBCL.