JOSE ARNALDO SHIOMI DA CRUZ
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
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- Is age an independent factor for prostate cancer? A paired analysis(2017) CRUZ, J. A. S. Da; PASSEROTTI, C. C.; REIS, S. T. Dos; GUARIERO, M. E. S.; CAMPOS, O. D. De; LEITE, K. R. M.; SROUGI, M.Introduction: Prostate cancer is the most prevalent malignant neoplasia among men worldwide. Several prognostic factors, including Gleason's score, the measurement of serum prostate-specific antigen (PSA) and the evaluation of the percentage of fragments affected by cancer on prostate biopsy, have already been established. Age alone, however, has yet to be studied as a prognostic factor independently from other known factors. The aim of the present study was to compare the characteristics and the evolution of prostate cancer in different age groups using a paired analysis for patients with equivalent known prognostic factors. In addition, we aimed to determine the true impact of age on the prognosis of prostate cancer. Material and Methods: The data from 2,283 patients subjected to radical retropubic prostatectomy between 1998 and 2009 were reviewed. The patients were divided into three age groups: < 55 years old, between 56 and 65 and > 65 years old. Each patient was matched to another patient in the other groups who had the same PSA range (< 4.0, between 4.0 and 10.0 and > 10), Gleason score on the surgical specimen and prognostic range of positive fragments in the prostate biopsy (< 33%, between 34 and 50% and > 50%). After pairing, each group consisted of 215 patients, who were compared using the biochemical recurrence of the disease (PSA > 0.2), the interval for biochemical relapse, extra-capsular invasion and invasion of the seminal vesicles or the lymph nodes. RESULTS. No significant difference was observed between the groups regarding the frequency of relapses, interval of relapse, extra-capsular invasion and invasion of the seminal vesicles or lymph nodes. Discussion: None of the studied factors were affected by the age of the patients. Therefore, patients of different ages had tumors with similar characteristics and behaviors. Conclusion: When assessed separately, without the effects of the main prognostic factors, age does not appear to be an independent prognostic factor for prostate cancer. © 2015 S. Karger AG, Basel.
- MMP-9 overexpression due to TIMP-1 and RECK underexpression is associated with prognosis in prostate cancer(2011) REIS, Sabrina Thalita; PONTES-JUNIOR, Jose; ANTUNES, Alberto Azoubel; SOUSA-CANAVEZ, Juliana Moreira de; DALL'OGLIO, Marcos Francisco; PASSEROTTI, Carlo C.; ABE, Daniel Kanda; CRIPPA, Alexandre; CRUZ, Jose Arnaldo Shiomi da; TIMOSZCZUK, Luciana M. S.; SROUGI, Miguel; LEITE, Katia R. M.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 and its specific inhibitors, TIMP-1 and RECK, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome in prostate cancer (PC). Methods: MMP-9, TIMP-1, and RECK expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue specimens collected from 79 patients with clinically localized PC submitted to radical prostatectorny (RP). Frozen benign prostatic tissue from another 10 men with prostate cancer, also submitted to RP, was analyzed to determine if the profile of gene expression was maintained. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). Results: In the tumor samples, MMP-9 was overexpressed by 9.2 times, and TIMP-1 and RECK were underexpressed (0.75 and 0.80 times, respectively). Overexpression of MMP-9 was significantly related to PSA levels above 10 ng/mL (p=0.033). In addition, MMP-9 overexpression was related to biochemical recurrence, with a marginal statistical significance (p=0.089). MMP-9 was also overexpressed in benign tissues of patients with PC, as were TIMP-1 and RECK, in contrast to their underexpression in tumor samples. Conclusion: Our results show that MMP-9 is overexpressed and its negative regulators are underexpressed in PC tissue, emphasizing a possible role of MMP-9 in the carcinogenesis process. Additionally, we noticed a relationship between MMP-9 overexpression and increased levels of PSA, an important prognostic factor. In benign tissue adjacent to tumors, the MMP-9 equilibrium is likely maintained because the expression of its negative regulators is preserved.
- Tgf-beta 1 expression as a biomarker of poor prognosis in prostate cancer(2011) REIS, Sabrina Thalita dos; PONTES-JUNIOR, Jose; ANTUNES, Alberto Azoubel; SOUSA-CANAVEZ, Juliana Moreira de; ABE, Daniel Kanda; CRUZ, Jose Arnaldo Shiomi da; DALL'OGLIO, Marcos Francisco; CRIPPA, Alexandre; PASSEROTTI, Carlo Camargo; RIBEIRO-FILHO, Leopoldo A.; VIANA, Nayara Izabel; SROUGI, Miguel; LEITE, Katia Ramos MoreiraOBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-beta 1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-beta 1 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 11 patients with benign prostate hyperplasia. The expression levels of TGF-beta 1 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-beta 1 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-beta 1, 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-beta 1 overexpression, 92.3% had poor prognostic features. CONCLUSIONS: TGF-beta 1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-beta 1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-beta 1 in prostate carcinogenesis.
- Underexpression of MMP-2 and its Regulators, TIMP2, MT1-MMP and IL-8, is Associated with Prostate Cancer(2012) REIS, Sabrina Thalita; ANTUNES, Alberto Azoubel; PONTES-JUNIOR, Jose; SOUSA-CANAVEZ, Juliana Moreira de; DALL'OGLIO, Marcos Francisco; PIANTINO, Camila Belfort; CRUZ, Jose Arnaldo Shiomi da; MORAIS, Denis Reis; SROUGI, Miguel; LEITE, Katia R. M.Objective: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specific regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). Materials and Methods: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the final outcome of the PCa. Results: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (>= 7) over-expressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). Conclusion: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.