Antonio Galia

Poly (ADP-ribose) Polymerase 1 Protein Expression in Normal and Neoplastic Prostatic Tissue

A genetic background has been implicated in the development of prostate cancer. Protein microarrays have enabled the identification of proteins, some of which associated with apoptosis, that may play a role in the development of such a tumor. Inhibition of apoptosis is a co-factor that contributes to the onset and progression of prostate cancer, though the molecular mechanisms are not entirely understood. Poly (ADP-ribose) polymerase 1 (PARP-1) gene is required for translocation of the apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. Hence, it is involved in programmed cell death. Different PARP-1 gene expression has been observed in various tumors such as glioblastoma, lung, ovarian, endometrial, and skin cancers. We evaluated the expression of PARP-1 protein in prostatic cancer and normal prostate tissues by immunohistochemistry in 40 men with prostate cancer and in 37 normal men. Positive nuclear PARP-1 staining was found in all samples (normal prostate and prostate cancer tissues). No cytoplasmic staining was observed in any sample. PARP-1-positive cells resulted significantly higher in patients with prostate carcinoma compared with controls (P<0.001). PARP-1 over-expression in prostate cancer tissue compared with normal prostate suggests a greater activity of PARP-1 in these tumors. These findings suggest that PARP-1 expression in prostate cancer is an attempt to trigger apoptosis in this type of tumor similarly to what reported in other cancers.

Is a single focus of low-grade prostate cancer diagnosed on saturation biopsy predictive of clinically insignificant cancer?

Objectives: To evaluate the incidence of indolent prostate cancer (PCa; <0.5 ml cancer and Gleason score, GS, ≤6) in men with microfocal PCa diagnosed on saturation biopsy (SPBx) submitted to radical retropubic prostatectomy. Methods: From January 2005 to December 2008, 413 patients (median age 61.5 years) underwent SPBx (median 30 cores). A single neoplastic microfocus (5% or less of cancer in a single core) was found in 55 men and all patients underwent retropubic prostatectomy. Median PSA was equal to 8.2 ng/ml, digital rectal examination was negative and GS was 6 in 40 cases and not evaluable in 15 cases. Results: Prostatectomy specimens showed a significant cancer in 48/55 (87.3%) patients with a median GS of 6.2 (range 5–8), presence of extraprostatic extension and positive surgical margins in 15 (27.3%) and 8 (14.5%) cases, respectively. Six patients had an indolent PCa, and in 1 case no tumor was found. Conclusions: Patients with a single microfocal PCa diagnosed on SPBx corresponded to an insignificant cancer in surgical specimens only in 12.7% of cases, but they should be informed that they may harbor more aggressive disease with a risk of non-organ-confined cancer that in our series was 27.3%.

Neuroendocrine Tumor in a Horseshoe Kidney

Renal neuroendocrine tumors (NET) are rare neoplasms of unknown histogenesis. To the best of our knowledge, 40 such cases have been described, 11 of which arising in horseshoe kidneys (HSK). We report an additional case of a NET associated with a HSK occurring in a 45-year-old man. A clinicopathological review of the reported cases together with an updated follow-up of such tumors arising in HSK is provided. The present data show that NET associated with HSK present a better prognosis than those occurring in normal kidneys, even over long-term follow-up periods.

PCA3 score and prostate cancer diagnosis at repeated saturation biopsy. Which cut-off: 20 or 35?

PURPOSE To compare PCA3 score cut-off of 35 vs 20 in PCa diagnosis in patients undergoing repeated saturation prostate biopsy (SPBx). MATERIAL AND METHODS From January 2010 to May 2011, 118 patients (median 62.5 years) with primary negative extended biopsy underwent a transperineal SPBx (median 30 cores) for persistent suspicion of PCa. The indications for repeated biopsy were: persistently high or increasing PSA values; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA ≤ 25% and ≤ 20 %, respectively; moreover, before performing SPBx urinary PCA3 score was evaluated. RESULTS All patients had negative DRE and median PSA was 8.5 ng/mL (range: 3.7-24 ng/mL). A T1c PCa was found in 32 patients (27.1 %): PCA3 score was 59 (median; range: 7-201) in the presence of PCa and 35 (median; range: 3-253) in the absence of cancer (p < 0.05). In the presence of ASAP and HGPIN median PCA3 score was 109 (range: 42-253) and 40 (range: 30-140), respectively. Diagnostic accuracy, sensitivity, specificity, PPV and NPV of PCA3 score cut-off of 20 vs 35 in PCa diagnosis were 44.9 vs 50 %, 90.6 vs 71.9 %, 27.9 vs 41.8 %, 31.9 vs 31.5 % and 88.9 vs 80 %, respectively. ROC analysis demonstrated an AUC for PCA3 ≥ 20 vs ≥ 35 of 0.678 and 0.634, respectively. CONCLUSIONS Our data suggest that PCA3 is more useful as an exclusion tool; moreover, setting a PCA3 cut-off at 20 vs 35, would have avoided 22.9 vs 38.1 % of biopsies while missing 9.4 % and 28 % diagnosis of PCa.

SPANX-B and SPANX-C (Xq27 region) gene dosage analysis in Sicilian patients with melanoma.

The incidence of melanoma has dramatically increased in many countries (it is 4.5 cases every 100 000 inhabitants in Sicily) and Xq27 region contains genes important in cancer like the SPANX (sperm protein associated with the nucleus in the X chromosome) gene family. These genes, made up of two exons separated by an intron of about 650 base pair, are expressed in sperm cells and in many tumours, including melanoma. These observations suggested that SPANX genes, or some of them, may be involved in melanoma development. The aim of this study was to investigate the genetic variability of SPANX-B and SPANX-C in a sample of Sicilian male population including patients with melanoma of the skin and controls. A total of 99 patients were enrolled in this study. They included: 17 male patients with cutaneous melanoma and 82 normal males. Semiquantitative fluorescent multiplex PCR dosage analysis was carried out to identify the variety of classes of SPANX-B and SPANX-C genes. Sixteen and 13 genetic classes were detected for SPANX-B and SPANX-C genes, respectively. A statistical significant difference for a particular class of SPANX-C gene was found comparing patients with melanoma and controls (P=0.011). Further investigations should be conducted to confirm these observations and to evaluate the possible implication of other genes of the region Xq27–28 in melanoma.

Is Transition Zone Sampling at Repeated Saturation Prostate Biopsy Still Useful

Objectives: To evaluate retrospectively the detection rate of prostate cancer (PCa) located only in the transition zone (TZ) by directed cores at repeated saturation prostate biopsy (SPB). Methods: From July 2001 to December 2009, 380 and 43 patients (median age: 63 years) underwent second and third SPB because they were persistently suspicious for PCa. Indications for biopsy were: prostate-specific antigen (PSA) of >10 ng/ml, and PSA between 4.1 and 10 ng/ml or 2.6 and 4 ng/ml with free/total PSA of ≤25 and ≤20%, respectively. A median of 23 cores were taken in the posterior zone, including 3 (median) cores in the TZ. The median PSA was 12.8 and 19.5 ng/ml and the digital rectal examination was positive in 36 (9.5%) and in no cases at second and third SPB, respectively. In patients with persistent and/or increasing PSA or abnormal free/total PSA values after negative second and third SPB, a transurethral prostate resection (TURP) was suggested to avoid the risk of missing a cancer localized in the TZ. Results: PCa was detected in the TZ only in 2/82 cases (2.5%), and in details in 1/79 (1.2%) and 1/3 (33.3%) of the men diagnosed at second and third SPB, respectively. After TURP, a PCa was found in 18/95 men (18.9%; 14 stage T1a and 4 stage T1b) and in 3/15 men (20%; 2 stage T1a and 1 stage T1b) previously having had negative second and third SPB. Conclusions: Sampling from the prostatic TZ by directed needle biopsies at repeated SPB was associated with a very low incidence of PCa (2.5%), especially if compared to TURP (19% detection rate), and could be omitted.

Is PCA3 Score Useful in Preoperative Staging of a Single Microfocus of Prostate Cancer Diagnosed at Saturation Biopsy

Objective: To evaluate prostate cancer gene 3 (PCA3) score accuracy in preoperative staging of cases of single microfocus of prostate cancer (PCa; less than 5% with Gleason score ≤6) diagnosed after repeat saturation biopsy (median 30 cores). Methods: From January 2009 to March 2012, 38 patients (median 64 years) with a microfocus of PCa, median PSA of 9.1 ng/ml and T1c clinical stage underwent radical retropubic prostatectomy. PCA3 score (cut-off of 20 vs. 35) was evaluated in predicting insignificant PCa (pIPCa: cancer volume <0.5 ml and Gleason score ≤6) versus organ-confined (OC) versus non-OC PCa. Results: Median PCA3 score results were equal to 10 versus 53 (p < 0.05) versus 108 (p < 0.05) in the presence of pIPCa (13.2%), versus OC (65.8%) versus non-OC PCa (21%), respectively. PCA3 scores were significantly correlated with tumor volume. Conclusions: A PCA3 score cut-off >20 in the presence of a microfocus of PCa is highly predictive of significant PCa (diagnostic accuracy equal to 86.8%) at definitive specimen.

Ameloblastoma of the Sinonasal Tract: Report of a Case with Clinicopathologic Considerations

Ameloblastomas are locally aggressive jaw tumours with a high propensity for recurrence and are believed to arise from remnants of dental lamina or odontogenic epithelium. Extragnathic ameloblastomas are unusual, and primary sinonasal tract origin is very uncommon with few cases reported in the literature. We herein report a case of primary sinonasal ameloblastoma presented in a 74-year-old male with nasal obstruction, rhinorrhoea, and sinusitis. Nasal endoscopy showed the right nasal cavity completely obstructed by a polypoid lesion attached to the lateral nasal wall. A preoperative CT scan was performed showing a solid lesion, measuring 2 cm in the maximum diameter, extending from the nasopharynx area with obstruction of the ostiomeatal unit and sphenoethmoidal recess into the lateral pharyngeal space, laterally to the parotid, without continuity with maxillary alveola and antrum. The tumour was completely excised endoscopically, and a final diagnosis of ameloblastoma was rendered. At the 12-month followup, there was no evidence of recurrence.

Genetic screening in young women diagnosed with endometrial cancer

Objective To evaluate the importance of Lynch syndrome associated risk screening in the patients aged less than 50 years affected from endometrial cancer. Methods From 2007 to 2014, 41 patients affected from endometrial cancer and aged less than 50 years underwent surgery at the Complex Operative Unit of Gynecology and Obstetrics, Cannizzaro Hospital of Catania, Italy. They were selected to undergo mismatch repair gene mutation analysis using immunohistochemistry (IHC; four markers: MLH1, MSH2, MSH6, PMS2) and microsatellite instability (MSI) test. For samples that resulted negative to IHC (abnormal finding), MSI test was performed to further study the suspected mutation. Samples were classified as MSI-high (MSI-H) if more than one marker was identified as unstable; MSI-low (MSI-L) if only one marker was identified as unstable; or MSI-stable (MSI-S) if no marker was identified as unstable. Samples were subdivided into two groups: MSI-H/L and MSI-S. Statistical analysis was performed to assess differences regarding survival, tumor staging, grading, and invasion of lymphovascular space between these two groups. Results IHC analysis showed that in 46% (19/41) of samples there was negative outcome. Forty-two percent (8/19) of these negative samples were unstable (either low or high). Of eight patients showing MSI, 75% were MSI-L, while 25% were MSI-H. Differences in survival, stage, grade, lymphovascular space invasion and Amsterdam criteria adherence were not statistically significant due to the small size of the cohort. Conclusion IHC and MSI test results of our cohort lead us to assess the relevance of performing Lynch syndrome genetic screening in endometrial cancer patients aged less than 50 years at the time of diagnosis.

Cerebellar degeneration-related autoantigen 1 (CDR1) gene expression in prostate cancer cell lines.

Prostate cancer (PCa) is the most frequent cancer among men in many developing countries, and the second leading cause of cancer-related death in men. A genetic component has been implicated in PCa onset and development. The cerebellar degeneration-related autoantigen 1 (CDR1) gene, mapping in Xq26-q27.2, is expressed in cerebrum, cerebellum, heart, lung, liver, and kidney. In addition, CDR1 expression has been detected in neuroblastoma, renal carcinoma cell lines, and other cancer cell lines. In this study, we investigated the expression of the CDR1 gene in the LNCaP and PC-3 PCa cell lines, and in the PNT1A normal prostate cell line. CDR1 mRNA expression was evaluated by qRT-PCR. We found that the CDR1 gene was overexpressed in the LNCaP and PC-3 PCa cell lines as compared with the PNT1A normal prostate cell line. These data suggest that CDR1 could be a new biomarker for PCa identification.