Telomeric zinc-finger associated protein (TZAP) in cancer biology: friend or foe?

The new identified protein telomeric zinc-finger associated protein (TZAP) is a negative regulator of telomere length. Since telomere length and telomere maintenance mechanisms are essential to cancer progression, TZAP is considered a new player in cancer biology. Here we aimed to analyze TZAP using the Cancer Genome Atlas data in a Pan-Cancer approach. We gathering data from TCGA Pan-Cancer studies utilizing cBioPortal, GEPIA and UALCAN. In total we analyzed 33 types of cancer (n=9664) and their respective controls (n=711). TZAP is transcribed in all cancers but less than 5% of all tumors show any somatic changes. TZAP was downregulated in kidney chromophobe carcinoma, and upregulated in esophageal cancer, head and neck squamous cell carcinomas, kidney renal clear cell carcinoma and in liver hepatocellular carcinoma. Globally, TZAP expression is related to favorable prognosis, associated to better overall and disease-free survival. Looking to specific tumors, TZAP expression has a dual behavior. Its downregulation is associated with poor prognosis in cervical squamous cell carcinoma, in kidney renal clear cell carcinoma, kidney papillary cell carcinoma, lung adenocarcinoma and pancreas adenocarcinoma. On the contrary, in adrenocortical carcinoma, colon and rectal cancer, brain lower grade glioma and prostate adenocarcinoma the upregulation of TZAP is related with poor prognosis. TZAP expression has a positive correlation with TRF1 and TRF2 in normal tissue but not in cancer. Our analyses indicate that TZAP has an important role in oncology and may be considered as a potential biomarker.

Matrix metalloproteinase-2 polymorphism is associated with prognosis in prostate cancer.

OBJECTIVE: Prostate cancer (PCa) is the most frequent tumor in males in Brazil. Single nucleotide polymorphisms (SNP) have been demonstrated in the promoter region of matrix metalloproteinases (MMPs) genes and have been associated with development and progression of some cancers. In this study, our aim was to investigate a possible relation between polymorphism of the promoter region of the MMP2 gene and classical prognostic parameters in prostate cancer. MATERIALS AND METHODS: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by real-time polymerase chain reaction, using fluorescent probes (TaqMan). RESULTS: In patients with tumors of a higher stage (pT3), a polymorphic allele in the MMP2 gene was more frequent (P = 0.026) than in patients with lower tumor stage. A polymorphic allele in the MMP2 gene was more frequent in Gleason ≥ 7 than in Gleason ≤ 6 (P = 0.042). CONCLUSIONS: We conclude that MMP2 polymorphism can be used together with pathological stage and Gleason score to identify patients with worse prognosis. Our results illustrate the potential use of MMP2 SNP as a molecular marker for prostate cancer.

Evaluation of the expression of integrins and cell adhesion molecules through tissue microarray in lymph node metastases of prostate cancer.

BACKGROUND: Integrins and adhesion molecules are responsible for the maintenance of the epithelial phenotype. Cell culture studies have reported the correlation between adhesion molecule expression and prostate carcinoma, but their role in the metastatic process is not yet known. Our aim is to study the expression profiles of these molecules and evaluate their association with the metastatic behavior of prostate adenocarcinoma. MATERIALS AND METHODS: A Tissue Microarray containing two samples from 19 primary tumors and one from their corresponding lymph node metastases was constructed and subjected to immunohistochemical analysis of the expression of integrins, E-cadherin and beta and gamma-catenins. Within each case, paired analyses were also performed to evaluate gains or losses in metastasis compared to its primary tumor. RESULTS: The expression of av, alphavbeta 3, alpha2beta 1 and gamma-catenin were abnormal in almost every case. Marked loss of E-cadherin and beta 4 integrin was found in primary and metastatic lesions. beta -catenin was normal in all primary cases and in 94% of metastases. a6 was normal in all primary tumors and metastases. alpha3 and alpha3beta 1 were normal in 32% of primary cases and in 53% and 6% of metastases, respectively. In paired analyses, loss of E-cadherin, beta 4, alphav, alpha3beta 1 and alphavbeta 3 was found in 65%, 71%, 59%, 53% and 47% of patients, respectively. Catenins and alpha2beta 1 showed maintenance of expression in most of the cases. CONCLUSIONS: In this preliminary study we have shown that the loss of cell adhesion molecules can be considered a characteristic of the metastatic phenotype in prostate cancer. Larger series should be evaluated in order to confirm our findings.

Upgrading the Gleason score in extended prostate biopsy: implications for treatment choice.

PURPOSE: To determine the incidence of overestimation of Gleason score (GS) in extended prostate biopsy, and consequently circumventing unnecessary aggressive treatment. METHODS AND MATERIALS: This is a retrospective study of 464 patients who underwent prostate biopsy and radical prostatectomy between January 2001 and November 2007. The GS from biopsy and radical prostatectomy were compared. The incidence of overestimation of GS in biopsies and tumor volume were studied. Multivariate analysis was applied to find parameters that predict upgrading the GS in prostate biopsy. RESULTS: The exact agreement of GS between prostate biopsy and radical prostatectomy occurred in 56.9% of cases. In 29.1% cases it was underestimated, and it was overestimated in 14%. One hundred and six (22.8%) patients received a diagnosis of high GS (8, 9, or 10) in a prostate biopsy. In 29.2% of cases, the definitive Gleason Score was 7 or lower. In cases in which GS was overestimated in the biopsy, tumors were significantly smaller. In multivariate analysis, the total percentage of tumor was the only independent factor in overestimation of GS. Tumors occupying less than 33% of cores had a 5.6-fold greater chance of being overestimated. CONCLUSION: In the extended biopsy era and after the International Society of Urological Pathology consensus on GS, almost one third of tumors considered to have high GS at the biopsy may be intermediate-risk cancers. In that condition, tumors are smaller in biopsy. This should be remembered by professionals involved with prostate cancer to avoid overtreatment and undesirable side effects.

Benign glandular inclusion in obturator lymph node of a man treated for prostate carcinoma.

Benign glandular inclusions in lymph nodes are extremely rare in men. Their identification is essential because it changes dramatically the prognosis and therapy of neoplasms. Described herein is the first case of benign glandular inclusion in an obturator lymph node dissected during a radical prostatectomy for treatment of prostate adenocarcinoma. A 60-year-old man underwent radical prostatectomy and obturator-hypogastric lymph node dissection for treatment of prostate adenocarcinoma. Benign glandular inclusion was found in microscopic examination. The lesion was characterized by two glandular spaces lined by a single, cuboid, benign epithelium localized in the sinus of one of four dissected lymph nodes. Immunohistochemistry showed mesothelial differentiation. Pathologists should be aware of benign glandular inclusion in obturator lymph nodes dissected during a radical prostatectomy for treatment of prostate cancer in order to avoid the incorrect diagnosis of metastatic disease.