Urinary matrix metalloproteinase‐7 level is associated with the presence of metastasis in bladder cancer

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Recent data suggest that MMP‐7 is critically involved in metastasis formation. In accordance, we formerly found significantly elevated MMP‐7 tissue expression and serum concentration in samples of patients with metastatic bladder cancer and observed an independent correlation between MMP‐7 levels and patients’ prognosis. In the present study we demonstrated that high preoperative urinary MMP‐7 concentrations are associated with metastatic bladder cancer.

OBJECTIVE

? To assess the presence of matrix metalloproteinase (MMP)‐7 in urine samples of patients with bladder cancer and to investigate the correlation between MMP‐7 urine concentration and clinicopathological variables.

PATIENTS AND METHODS

? The presence of MMP‐7 in the urine of patients with bladder cancer was tested in 32 representative cases using immunoprecipitation followed by western blot analysis. ? Urinary MMP‐7 concentration levels were analyzed in 132 patients with bladder cancer and 96 controls using an enzyme‐linked immunosorbent assay.

RESULTS

? MMP‐7 levels did not differ significantly between patients with localized bladder cancer and controls (P= 0.174). On the other hand, we detected a fourfold, significantly elevated MMP‐7 concentration in urine samples of patients with bladder cancer with regional or distant metastasis (P= 0.003). ? Using a threshold value of 6.88 ng/ml, determined by receiver‐operating characteristic curve analysis, a specificity of 82% and a sensitivity of 78% were observed. ? Western blot analysis revealed that the 55‐kDa tissue inhibitor of metalloproteinase 1 complexed MMP‐7 is the dominant form of urinary matrilysin.

CONCLUSIONS

? MMP‐7 is present in detectable amounts in the urine of patients with bladder cancer. Its concentrations are significantly elevated in patients with metastatic disease. ? Determination of urinary matrilysin level could help to detect bladder cancer metastasis, and may therefore provide a more reliable prognosis and influence therapy decisions.     

Albinism, or the NOACH syndrome

After a 4-year multidisciplinary study of albinism our findings will be presented here. Over a hundred albinos were examined, together with their heterozygote family members. Given this substantial patient and subject sample we were provided with the opportunity to: evaluate the results of standard diagnostic procedures, for example pedigree analysis, ocular and clinical examination; determine the diagnostic value of biochemical, and ultrastructural tests; and develop a new and viable albino diagnostic protocol, particularly for electrophysiological examination. In the conclusions the following subjects are in order: Diagnosis: Our most important finding up till now is that normally pigmented people who do not look like albinos can in fact be albinos. Differential diagnosis: It appears that patients with autosomal recessive albinism can be normally pigmented, and patients with X-linked albinism can be severely hypopigmented. We therefore propose to abandon the terms oculo-cutaneous albinism (OCA), and X-linked ocular albinism (XOA), and use the terms autosomal recessive albinism, and X-linked albinism instead. X-linked albinism Forsius-Eriksson type (XOAF): We assume that XOAF does not represent a true form of albinism. Classification: Our results indicate that the phenotypical albino classification, which was a base for Witkop et al. (1978) to also obtain a genetical classification, supported by the hairbulb test, has not proved to be useful for the classification of tyrosinase negative (TNOCA), tyrosinase positive oculocutaneous albinism (TPOCA), and autosomal recessive ocular albinism (AROA) as genetically distinct forms. Prevalence: Our prevalence estimate for all forms of albinism is at least 1:15,000, about 10% of the albinos have X-linked albinism. Definition: We want to modify the albino definition as a hereditary and congenital inborn error of metabolism related to the pigment cell, and resulting in a systemic disorder that is characterized by anomalies of eyes, and hypopigmentation in most cases or absence of pigment in skin, hair, and eyes, and of which the neuro-anatomical consequences are the most characteristic.     

Prognostic value of tissue and circulating levels of IMP3 in prostate cancer

Tissue levels of the oncofetal protein insulin‐like growth factor 2 (IGF2) messenger RNA‐binding protein 3 (IMP3) have been associated with poor prognosis in multiple human malignancies. However, its circulating levels have not yet been analyzed. Therefore, the aim of this study was to assess the prognostic value of both serum and tissue levels of IMP3 in prostate cancer (PC). IMP3 protein expression was analyzed in 124 PC and 13 benign prostate hyperplasia (BPH) patients using immunohistochemistry. Gene expression levels of IMP3 and its molecular target IGF2 were analyzed in 29 frozen and 26 paraffin‐embedded PC tissues using real‐time polymerase chain reaction and immunohistochemistry. Serum IMP3 levels were assessed in 94 PC and 20 BPH patients as well as in 20 controls using enzyme‐linked immunosorbent assay. IMP3 immunostaining was present in 0% (0/13) of BPHs, 15% (15/101) of clinically localized PCs and 65% (15/23) of palliatively treated metastatic PCs (p < 0.001). Accordingly, serum IMP3 concentrations were significantly higher in PC compared to BPH patients which were higher than those in controls (p < 0.001 each). The highest concentrations were detected in metastatic PC patients (p = 0.036). In patients who underwent radical prostatectomy high IMP3 serum levels were independently associated with poor cancer‐specific survival. IMP3 gene and protein expressions were not correlated with those of IGF2. In conclusion, we found enhanced IMP3 levels in tissue and serum samples of PC patients compared to non‐PC men. Moreover, IMP3 was associated with metastasis and PC‐specific survival. The tumor promoting effect of IMP3 appears to be independent from its regulatory role on IGF2 in PC.     

Gonadal function recovery in very long-term male survivors of childhood cancer

BackgroundAlthough gonadal toxicity has been reported, no data are available on recovery of gonadal function in very long-term survivors of childhood cancer. Inhibin B is a novel reliable serum marker which has been shown to be of value in childhood cancer survivor studies to identify risk groups for impaired gonadal function, but consecutive long-term follow-up studies using serum inhibin B as a marker are not available.ObjectiveTo evaluate possible recovery of gonadal dysfunction over time in adult male survivors of childhood cancer.MethodsIn this retrospective study, adult male long-term childhood cancer survivors (n = 201) who visited our outpatient late effects clinic were included and we used inhibin B as a surrogate marker for gonadal function.ResultsMedian age at diagnosis was 5.9 years (range 0.0–17.5) and discontinuation of treatment was reached at a median age of 8.2 years (range 0.0–20.8). Inhibin B levels were first measured after a median follow-up time of 15.7 years (range 3.0–37.0). Median interval between the first (T1) and second measurement (T2) was 3.3 years (range 0.7–11.3). Median inhibin B level was 127 ng/L (range 5–366) at T1 and 155 ng/L (range 10–507) at T2. The prediction model suggests that inhibin B levels do not normalise in survivors with a very low Inhibin B level at T1.ConclusionsOur results suggest that recovery of gonadal function is possible even long after discontinuation of treatment. However, this recovery does not seem to occur in survivors who already reached critically low inhibin B levels after discontinuation of treatment.     

Rapid detection of human cytomegalovirus DNA in peripheral blood leukocytes of viremic transplant recipients by the polymerase chain reaction

Peripheral blood leukocyte samples (n = 458) of 24 bone marrow transplant and 52 kidney transplant patients were examined weekly for the presence of human cytomegalovirus (HCMV) using an improved culture technique (DEAFF; detection of early antigen fluorescent foci). In total 5 (21%) bone marrow transplant and 11 (21%) kidney transplant patients developed a viremia. Patients' samples were investigated for the presence of HCMV DNA using an in vitro DNA amplification technique, the polymerase chain reaction (PCR). From the statistically evaluable viremic patients (n = 13), 110 blood samples were analyzed. In 5 of these patients, the DEAFF and PCR led to identical results. In 8 patients however the PCR was more sensitive, i.e. HCMV DNA was detected for a longer period of time. Applying statistical analysis using the McNemar test, this result was significant (P less than 0.05). The PCR applied on leukocyte samples did not detect HCMV DNA in viruric patients without viremia. Moreover, the current PCR never led to positive results with peripheral blood leukocyte samples of healthy seropositive or seronegative controls. Since the PCR can be performed in 6 hr, this technique will contribute to rapid detection of HCMV DNA in peripheral blood leukocytes and therefore to optimal clinical management of HCMV-infected transplant recipients.     

Åland eye disease: no albino misrouting

Electrophysiological studies showed that a patient with Åland eye disease had no misrouting of the optic pathways which is always found in all forms of albinism as a consequence of the retinogeniculate anomaly. Also the spontaneous and optokinetic nystagmus did not resemble that of the large majority of human albinos. The marked asymmetry found in this patient seems to be typical for humans with a defective development of foveal binocular vision. These findings are in agreement with clinical, nystagmographic and EM findings that Åland eye disease is distinct from the Nettleship-Falls type of X–linked ocular albinism. Furthermore, Åland eye disease is different from X-chromosomal congenital stationary night blindness with myopia by the fact that the scotopic functions are only moderately affected and there is no restriction of the peripheral photopic visual fields. In addition, there is latent nystagmus of extraocular type that appears also in female carriers. There is no ophthalmoplegia, there is a progression of the myopia and the dyschromatopsia is of secondary type.