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.

Cytosol cathepsin D in Thai women with breast cancer.

The necessity of screening high-risk patients with breast cancer who may require more intensive systemic therapy especially in the node negative subgroup was generally accepted. Cathepsin D, an estrogen induced protease, has been shown to be implicated in the proliferation and invasion of breast cancers. Retrospective assessment of cytosol cathepsin D in 151 primary breast cancers was done together with ER, PR and other clinico-pathological parameters. No significant relationship was shown between cathepsin D concentrations or cathepsin D status using median value of 56 pmol/mg protein as cutoff level with most studied parameters. High cathepsin D status was found in 47 per cent of patients with fibrocystic disease of breast and 30 per cent in node-negative, ER-PR negative tumors. Survival analysis after 5 or 10 year follow-up and evaluation in a larger scale are necessary before including cytosol cathepsin D measurement as a routine clinical investigation for breast cancers.