Multiparametric Magnetic Resonance Imaging of the Prostate for Tumour Detection and Local Staging: Imaging in 1.5T and Histopathologic Correlation.

PURPOSE: The study sought to prospectively evaluate which technique among T2-weighted images, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), diffusion-weighted (DW) MRI, or a combination of the 2, is best suited for prostate cancer detection and local staging. METHODS: Twenty-seven consecutive patients with biopsy-proven adenocarcinoma of the prostate underwent MRI on a 1.5T scanner with a surface phased-array coil prior radical prostatectomy. Combined anatomical and functional imaging was performed with the use of T2-weighted sequences, DCE MRI, and DW MRI. We compared the imaging results with whole mount histopathology. RESULTS: For the multiparametric approach, significantly higher sensitivity values, that is, 53% (95% confidence interval [CI]: 41.0-64.1) were obtained as compared with each modality alone or any combination of the 3 modalities (P < .05). The specificity for this multiparametric approach, being 90.3% (95% CI: 86.3-93.3) was not significantly higher (P < .05) as compared with the values of the combination of T2+DCE MRI, DW+DCE MRI, or DCE MRI alone. Among the 3 techniques, DCE had the best performance for tumour detection in both the peripheral and the transition zone. High negative predictive value rates (>86%) were obtained for both tumour detection and local staging. CONCLUSIONS: The combination of T2-weighted sequences, DCE MRI, and DW MRI yields higher diagnostic performance for tumour detection and local staging than can any of these techniques alone or even any combination of them.

Study of genetic and epigenetic alterations in urine samples as diagnostic markers for prostate cancer.

BACKGROUND: Early diagnosis of prostate cancer and identification of new prognostic factors remain main issues in prostate cancer research. In this study, we sought to test a panel of cancer-specific markers in urine samples as an aid for early cancer diagnosis. MATERIALS AND METHODS: Sedimented urine samples of 66 candidates for needle biopsy were tested. Real time-polymerase chain reaction (RT-PCR) was applied to detect the expression of transmembrane protease serine-2 and Ets-related gene fusion (TMPRSS2-ERG), Ets-related gene (ERG), prostate cancer antigen-3 (PCA3), and serine peptidase inhibitor kazal type-1 (SPINK1) transcripts. For testing of the methylation status of Glutahione S-tranferase P (GSTP1) and Ras association domain family member-1(RASSF1A) promoter region, methylation-specific PCR (MSP-PCR) was applied. RESULTS: Among the tested parameters, the presence of TMPRSS2-ERG (OR=9.044, 95% CI=2.207-37.066, p=0.002), as well as a positive test result for PCA3 (OR=7.549, 95% CI=1,858-30,672, p=0.005) were associated with the subsequent diagnosis of prostate cancer. A multivariable logistic regression including all the significantly associated variables [prostate-specific antigen (PSA), digital rectal examination (DRE), TMPRSS2-ERG and PCA3], yielded a model with area under the receiver-operating characteristic curve (AUC) =0.894 (95% CI=0.772-1.00). CONCLUSION: A multiplexed quantitative PCR analysis on sedimented urine, in conjunction with the results of serum PSA levels and DRE, has the potential to accurately foresee subsequent needle biopsy outcomes. On the basis of the above, algorithms may be designed to guide decisions for needle biopsy.

Human papillomavirus genotyping and e6/e7 mRNA expression in greek women with intraepithelial neoplasia and squamous cell carcinoma of the vagina and vulva.

A large proportion of vaginal and vulvar squamous cell carcinomas (SCCs) and intraepithelial neoplasias (VAIN and VIN) are associated with HPV infection, mainly type 16. The purpose of this study was to identify HPV genotypes, as well as E6/E7 mRNA expression of high-risk HPVs (16, 18, 31, 33, and 45) in 56 histology samples of VAIN, VIN, vaginal, and vulvar SCCs. HPV was identified in 56% of VAIN and 50% of vaginal SCCs, 71.4% of VIN and 50% of vulvar SCCs. E6/E7 mRNA expression was found in one-third of VAIN and in all vaginal SCCs, 42.9% of VIN and 83.3% of vulvar SCCs. Our data indicated that HPV 16 was the commonest genotype identified in VAIN and VIN and the only genotype found in SCCs of the vagina and vulva. These findings may suggest, in accordance with other studies, that mRNA assay might be useful in triaging lesions with increased risk of progression to cancer.

Evaluation of kallikrein-related peptidase 5 expression and its significance for breast cancer patients: association with kallikrein-related peptidase 7 expression.

BACKGROUND: Kallikrein-related peptidases (KLKs) have been proposed as potential cancer biomarkers. Contradictions in literature led us to clarify the role of KLK5 as a breast cancer predictor, as well as its association with KLK7 expression. PATIENTS AND METHODS: Semi-quantitative RT-PCR detected KLKs 5 and 7 in 80 breast tissues, 74 neoplastic and 6 normal. Steroid hormone receptors were quantified in all samples. Associations between KLK5 status and clinicopathological variables, as well as disease-free survival (DFS) and overall survival (OS) of patients were analyzed. RESULTS: Forty tumor tissues showed high KLK5 expression, which was significantly associated with estrogen receptor status. Significant co-expression of KLKs 5 and 7 was observed in the same cancer samples (p=0.02). Increased KLK5 expression was a statistically significant independent prognostic factor for DFS (p=0.009 univariate analysis and p=0.028 multivariate analysis) and OS of patients (p=0.014, univariate analysis). CONCLUSION: Increased KLK5 expression can contribute to the prognosis of DFS and OS of breast cancer patients. KLKs 5 and 7 are co-expressed in breast cancer.

Clinical evaluation of PRMT1 gene expression in breast cancer.

Methylation of arginine residues has been implicated in many cellular activities like mRNA splicing, transcription regulation, signal transduction and protein-protein interactions. Protein arginine methyltransferases are the enzymes responsible for this modification in living cells. The most commonly used methyltransferase in man is protein arginine methyltransferase 1 (PRMT1). Since methylation processes appear to interfere in the emergence of several diseases, including cancer, we investigated the localisation of the protein in cancer tissue and, for the first time, the relation that possibly exists between the expression of PRMT1 gene and breast cancer progression. We used tumour specimens from 62 breast cancer patients and semi-quantitative RT-PCR to determine the expression of PRMT1 gene and was found to be associated with patient's age (p = 0.002), menopausal status (p = 0.006), tumour grade (p = 0.03), and progesterone receptor status (p = 0.001). Survival curves revealed that PRMT1-v1 status-low expression relates to longer disease-free survival (DFS; p = 0.036). To the contrary, PRMT1-v2 status is not associated neither with the clinical or pathological parameters nor with DFS (p = 0.31). PRMT1-v3 was not statistically significantly expressed in breast cancer tissue. Selected cancer and normal breast samples were stained for PRMT1. In both normal and cancerous breast tissues, staining was in the cytoplasm and only in rare cases the cell nucleus appeared stained. Present results show a potential use for this gene as a marker of unfavourable prognosis for breast cancer patients.

Isomorph expression of BAG-1 gene, ER and PR in endometrial cancer.

BACKGROUND: BAG-1 isomorphs are regulating proteins with antiapoptotic action in endometrium. ERa and PRA isomorphs seem to have an important role in endometrial cancer. PATIENTS AND METHODS: We investigated the expression of BAG-1, ERa and PRA isomorphs in endometrioid adenocarcinoma and we correlated them with clinicopathological findings of the tumor. Fresh endometrial tissues were obtained from 33 patients with endometrial carcinoma and 191 paraffin-embedded tissues were analyzed by real-time PCR and immunochemistry for BAG-1, ER and PR. RESULTS: BAG-1 protein is expressed in both nucleus and cytoplasm. Grade 3 tumors were considered to have the highest intensity. Only 4 out of 79 samples showed intense expression of ERa, while 37 samples out of 72 samples strongly expressed PRA. CONCLUSION: BAG-1 nuclear isomorph appeared more frequently in grade 2 tumors than in grade 1 and 3 tumors, and the cytoplasmatic isomorph was expressed more strongly than the nuclear one.

BCL-2, BAX and P53 expression profiles in endometrial carcinoma as studied by real-time PCR and immunohistochemistry.

BACKGROUND: Apoptotic genes regulate apoptosis by the action of their pro- and antiapoptotic products. Among the most important proteins are p53 and Bcl-x family proteins. PATIENTS AND METHODS: The differential expression of these apoptotic genes were analyzed in relation to clinicopathological criteria in women with endometrial carcinoma. Thirty-three fresh tissues and 191 paraffin-embedded tissues were analyzed by real-time PCR for bcl-2/bax ratio and immunohistochemistry for p53, bcl-2 and bax proteins. RESULTS: Bcl-2/bax ratio tended to increase in grade 3 samples compared to grade 1 tumors. Mutated p53 was frequently observed in serous-papillary endometrial carcinomas (p=0.018). Low (<10%) and moderate (10-50%) expression of mutated p53 was observed in tumors with high expression of bax protein (>0.7). CONCLUSION: The Bcl-2/bax ratio is increased in grade 3 tumors. Bax protein shows a strong tendency for expression in the third group of clinical staging (stage IIb, III and IV). Poorly differentiated tumors highly expressed mutated p53.

PGP 9.5 and cyclin D1 coexpression in cutaneous squamous cell carcinomas.

BACKGROUND: squamous cell carcinoma (SCC) consists of altered keratinocytes, presents variable differentiation, inexorably progresses, and on occasion metastasizes. OBJECTIVE: to investigate the biological activity of epidermal cells in SCCs by estimating the expression of PGP 9.5 and cyclin D1 using immunohistochemistry. METHODS: the sample included 13 well-differentiated cases of cutaneous SCC (grade I), 12 moderately differentiated tumors (grade II), and 7 poorly differentiated lesions (grade III). Four cases belonged to the distinct entity of pseudoadenoid SCC. RESULTS: PGP 9.5 expression was positively correlated with tumor stage (P < .001) and potential perineural invasion ( P < .001), whereas cyclin D1 expression correlated inversely with the degree of cellular differentiation (P < .001) and PGP 9.5 immunostaining (P < .001). CONCLUSION: PGP 9.5 and cyclin D1 coexpression was closely associated with tumor aggressiveness and can be classified as a marker for predicting the outcome of resection-treated skin cancer patients.