Expression of urokinase-type plasminogen activator and its receptor in squamous cell carcinoma of the oral tongue

Abstract Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) act in the proteolysis of basement membrane and extracellular matrix structures, facilitating tumor invasion. The purpose of this study was to evaluate the relationship between these proteins and clinicopathological parameters in squamous cell carcinoma of the oral tongue (SCCOT). Sixty cases of SCCOT were submitted to immunohistochemistry and analyzed semiquantitatively at the invasion front and in the tumor core. The results were associated with lymph node metastasis, clinical stage, locoregional recurrence, clinical outcome and histological grade of malignancy. A higher expression of uPA was observed in cases of tumors of high-grade versus low-grade malignancy (p = 0.010). Moreover, the cases with the worst pattern of invasion presented an overexpression of uPA (p = 0.011). The presence of locoregional recurrence was associated with uPAR (p = 0.039), and the expression of both biomarkers was much higher at the invasion front than in the tumor core (p < 0.001). The results suggest uPA and uPAR are involved in the progression and aggressiveness of SCCOT, mainly at the tumor-host interface.

Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer

Introduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.

Correlation between Beta1 integrin expression and prognosis in clinically localized prostate cancer

Integrins are transmembrane glycoprotein receptors that regulate cell-matrix interactions, thus functioning as sensors from the environment. They also act as cell adhesion molecules that are responsible for the maintenance of the normal epithelial phenotype. Some studies have reported a correlation between carcinogenesis and changes in integrin expression, especially β1 integrin, however its role in prostate cancer (PC) is unclear. The aim of our study was to evaluate the expression of β1 integrin in localized PC and to correlate the pattern of expression with recurrence after surgical treatment. Methods For this case-control study, we retrospectively selected surgical specimens from 111 patients with localized PC who underwent radical prostatectomy. Recurrence was defined as a PSA level exceeding 0.2ng/mL after surgery, and the median follow-up was 123 months. Integrin expression was evaluated by immunohistochemistry in a tissue microarray containing two samples from each tumor. We employed a semiquantitative analysis and considered a case as positive when the expression was strong and diffusely present. Results: There was a loss of 11 cases during the tissue micro array assembling. β1 expression was positive in 79 of the 100 evaluated cases (79%). The univariate and multivariate analyses showed that the negative expression of β1 integrin was associated with biochemical recurrence (p = 0.047) and time to recurrence after radical prostatectomy (p = 0.023). When β1 was negative, the odds ratio for recurrence was 2.78 times higher than that observed in the positive cases [OR = 2.78, p = 0.047, IC 95% (1.01-7.66)]. Conclusions: The loss of β1 integrin immune expression was correlated with biochemical recurrence in patients treated with radical prostatectomy for localized PC.

Identificación de factor de crecimiento vascular endotelial en células glandulares de tejido prostético maligno y benigno: Relación con la recidiva tumoral al año de la prostatectomía / Vascular endothelial growth factor in malignant and non malignant prostatic tissue: Association with tumor recurrence at one year after prostatectomy

Background: Prostate cancer (PC) is the second cause of death by cancer in men in Chile. Its behavior is so variable that it is necessary to search reliable prognostic markers. Vascular Endothelial Growth Factor (VEGF) is one of the most powerful pro-angiogenic factors. There is no agreement on its validity as a diagnostic or prognostic factor. Aim: To search for VEFG in prostatic tissue. Material and Methods: This study was performed in prostatectomy tissue coming from 41 patients with PC and 39 patients with benign prostatic hyperplasia (BPH). Specimens were studied using immunohistochemical staining for VEGF. The percentage of stained glandular cells per patient was calculated and associated with pathological diagnosis in cancer patients. Results: PC biopsies had a mean of 82% of VEGF (+) stained cells, while BPH had only 1.6% (p < 0.01). No relationship was found between the percentage of staining and recurrence at one year of follow-up in the case of PC. Conclusions: These results would rule out VEGF as a prognostic factor in this series of patients.

La eliminación de células prostáticas circulantes primarias en sangre posterior a la prostatectomía radical disminuye el riesgo de recidiva bioquímica / Elimination of primary circulating prostate cells after radical prostatectomy for prostate cancer decreases the risk of future biochemical failure

OBJETIVO: Las células prostáticas circulantes en sangre (CPCs) primarias son aquellas células prostáticas detectadas en pacientes con cáncer de próstata antes del tratamiento quirúrgico radical, por el contrario, las CPCs secundarias son aquellas detectadas posterior a este tratamiento. Pese a que las CPCs primarias son encontradas frecuentemente en pacientes con cáncer de próstata, solo unas pocas sobreviven y formarán metástasis. Evaluamos la asociación de las CPCs primarias y secundarias con la recidiva bioquímica en hombres con cáncer de próstata tratados con prostatectomía radical. MÉTODOS: Se tomaron muestras de sangre seriadas antes y después del tratamiento quirúrgico, se obtuvieron células mononucleares por centrifugación diferencial y se identificaron las CPCs utilizando inmunocitoquímica. Los datos de edad, estadio patológico, grado patológico, márgenes quirúrgicos, extensión extracapsular, perineural, vascular e infiltración linfática fueron comparados con la presencia o ausencia de CPCs en pacientes con o sin recidiva bioquímica. Se utilizo el método de Kaplan Meyer para comparar la sobrevida libre de enfermedad de los pacientes con o sin CPCs. RESULTADOS: 138 de 423 (32,6%) de los hombres que fueron sometidos a una biopsia prostática por un PSA elevado tuvieron cáncer de próstata, de estos hombres, 15 (10,9%) fueron negativos para CPCs. De los hombres positivos, 95 fueron sometidos a una prostatectomía radical, no existió relación entre la detección de CPCs primarias y los parámetros clínico - patológicos del cáncer, sin embargo, los pacientes con CPCs secundarias se asociaron con mayor tasa de recidiva bioquímica. CONCLUSIONES: Las CPCs primarias son frecuentemente detectadas en hombres con cáncer de próstata, pero no se asocian con recidiva bioquímica, por lo tanto pueden ser útiles para la detección de cáncer de próstata pero no para su pronóstico. La detección de CPCs posterior a la cirugía se asocia con mayores posibilidades de recidiva bioquímica

OBJECTIVES: Primary CPCs are those detected in the blood of prostate cancer patients before radical treatment; secondary CPCs are those detected afterwards. Although primary CPCs are frequently found, it has been suggested that only a few will survive and go on to form metastasis. We evaluate the frequency of primary and secondary CPC detection and the association with biochemical failure, relation with clinical-pathological parameters and clinical implications in men treated by radical prostatectomy (RP) for prostate cancer. METHODS: Serial blood samples were taken before surgery and during follow up after RP. Mononuclear cells were obtained by differential gel centrifugation, and CPCs were identified using standard immunocytochemistry using anti-PSA monoclonal antibodies. Age, pathological stage (organ confined, non organ confined), pathological grade, margin status (positive, negative), extracapsular extension, perineural, vascular, and lymphatic infiltration (positive, negative) were compared with the presence/absence of CPCs in patients with and without biochemical failure. Kaplan Meier method was used to compare the unadjusted biochemical failure free survival of patients with and without CPCs. RESULTS: 138 of 423 (32.6%) men undergoing prostate biopsy for an elevated serum PSA were diagnosed of prostate cancer. Of these men 15 (10.9%) were CPC negative. 95 CPC positive men underwent RP. There was no relation between primary CPC detection and clinical-pathological parameters; however, secondary CPCs were associated both with clinical-pathological parameters and biochemical failure. CONCLUSIONS: Primary CPCs are frequently detected in men with prostate cancer, but they are not associated with biochemical failure, so that they may be useful for prostate cancer detection but not for prognosis. The persistence of CPCs after surgery is associated with increased biochemical failure