Donatas Petroska

Combined Analysis of TMPRSS2-ERG and TERT for Improved Prognosis of Biochemical Recurrence in Prostate Cancer

Prostate cancer (PCa) is a heterogeneous disease with diverse clinical outcomes. TMPRSS2–ERG is the most common gene fusion in PCa, whereas activation of telomerase is a common feature of various malignancies. The aim of our study was to explore the combined utility of these and some other biomarkers in predicting biochemical recurrence after radical prostatectomy. Prostate specimens and urine sediments from 179 previously untreated patients with pT2‐pT3 stage PCa were analyzed for expression of telomerase (TERT and TR) and the TMPRSS2–ERG fusion gene by means of reverse transcription PCR. Real‐time PCR was used for quantification of ERG and SPINK1 expression. In total, 74% (117/158) of the prostate adenocarcinomas were positive for the TMPRSS2–ERG and/or TERT expression. Noninvasively, these transcripts were identified in 31% (19/61) of catheterized urine specimens. Significantly higher expression of ERG was detected in TMPRSS2–ERG‐positive tumors (P < 0.0001), whereas more intense expression of SPINK1 was characteristic for the TMPRSS2–ERG‐negative tumors (P = 0.003). TERT‐positive cases also had elevated levels of ERG (P = 0.016), suggesting a possible link between aberrant expression of ERG and reactivation of TERT in prostate tumors. The cases negative for both transcripts, TMPRSS2–ERG and TERT, rarely recurred (P = 0.014) and showed significantly longer biochemical recurrence‐free period (P = 0.022) as compared to the TMPRSS2–ERG and/or TERT‐positive cases. The results of our study suggest that combined analysis of TMPRSS2–ERG and TERT expression can be a valuable tool for early prediction of biochemical recurrence of PCa after radical prostatectomy.

Ocular surface reconstruction using amniotic membrane following excision of conjunctival and limbal tumors.

Purpose To report the clinical results of patients treated by preserved human amniotic membrane transplantation (AMT) following the removal of conjunctival and limbal tumors. Methods Retrospective noncomparative interventional case series of 9 patients (9 eyes) who underwent AMT after removal of conjunctival and limbal tumors with lesion-free margins and perilesional cryotherapy. Results The excised tumors were histopathologically examined and included 2 squamous cell carcinomas, 2 papillomas, and 5 nevi. Bulbar conjunctiva was involved in all of the eyes, limbus and cornea in 7 and 3 eyes, respectively. The mean extent of the limbal involvement was 4 clock hours (range 2–9, SD 2.4); the average diameter of the base of the tumor was 12.8 mm (range 10–20, SD 4.4). The mean follow-up time was 38 months (range 13–60, SD 15). No surgical or early postoperative complications were observed. In all eyes, complete healing of the tissue defect occurred, resulting in a stable, wet, and noninflamed epithelium. All eyes demonstrated a smooth ocular surface except one with a clinically insignificant Symblepharon after the excision of a squamous cell carcinoma. Superficial peripheral corneal vascularization and opacification as a sign of partial limbal stem cell deficiency developed in 2 eyes. In one case, a recurrence of conjunctival papilloma was diagnosed after a 3-year follow-up. Conclusions Amniotic membrane transplantation is an effective method of reconstruction following a conjunctival and limbal tumor excision and cryotherapy of surgical wound margins. In most cases, complete healing of an ocular surface can be achieved without any clinically significant complications.

Inflammatory myopathy in a patient with Aicardi-Goutières syndrome.

Aicardi-Goutières syndrome (AGS) is an inflammatory disorder belonging to the recently characterized group of type I interferonopathies. The most consistently affected tissues in AGS are the central nervous system and skin, but various organ systems and tissues have been reported to be affected, pointing to the systemic nature of the disease. Here we describe a patient with AGS due to a homozygous p.Arg114His mutation in the TREX1 gene. The histologically proven inflammatory myopathy in our patient expands the range of clinical features of AGS. Histological signs of muscle biopsies in the proband, and in two other AGS patients described earlier, are similar to those seen in various autoimmune myositises and could be ascribed to inapproapriate IFN I activation. In view of signs of possible mitochondrial damage in AGS, we propose that mitochondrial DNA could be a trigger of autoimmune responses in AGS.

Decreased expression of MT1E is a potential biomarker of prostate cancer progression

Differentiation of indolent and aggressive prostate carcinoma (PCa) at the time of diagnosis is currently one of the major challenges. This study aimed at identification of prognostic biomarkers to aid in predicting biochemical recurrence (BCR) of the disease. Microarray-based gene expression profiling in tissues of 8 BCR and 8 No-BCR cases revealed expression differences of 455 genes, most of which were down-regulated in BCR cases. Eleven genes were selected for validation by real-time PCR in the first PCa cohort (N = 55), while seven of them were further validated in the second, independent, PCa cohort (N = 53). Down-regulation of MT1E (p < 0.001) and GPR52 (p = 0.002) expression and up-regulated levels of EZH2 (p = 0.025) were specific biomarkers of BCR in at least one of the two PCa cohorts, but only MT1E expression retained the independent prognostic value in a multivariate analysis (p < 0.001). DNA methylation analysis (114 PCa and 24 non-cancerous tissues) showed frequent MT1E methylation in PCa (p < 0.001) and was associated (p < 0.010) with the down-regulated expression in one PCa cohort. The results of our study suggest MT1E down-regulation as a potential feature of aggressive PCa.Differentiation of indolent and aggressive prostate carcinoma (PCa) at the time of diagnosis is currently one of the major challenges. This study aimed at identification of prognostic biomarkers to aid in predicting biochemical recurrence (BCR) of the disease. Microarray-based gene expression profiling in tissues of 8 BCR and 8 No-BCR cases revealed expression differences of 455 genes, most of which were down-regulated in BCR cases. Eleven genes were selected for validation by real-time PCR in the first PCa cohort (N = 55), while seven of them were further validated in the second, independent, PCa cohort (N = 53). Down-regulation of MT1E (p < 0.001) and GPR52 (p = 0.002) expression and up-regulated levels of EZH2 (p = 0.025) were specific biomarkers of BCR in at least one of the two PCa cohorts, but only MT1E expression retained the independent prognostic value in a multivariate analysis (p < 0.001). DNA methylation analysis (114 PCa and 24 non-cancerous tissues) showed frequent MT1E methylation in PCa (p < 0.001) and was associated (p < 0.010) with the down-regulated expression in one PCa cohort. The results of our study suggest MT1E down-regulation as a potential feature of aggressive PCa.

Death Caused by Hepatodiaphragmatic Interposition of the Colon

Hepatodiaphragmatic interposition of the colon is a rare, usually asymptomatic, anomaly and is typically an incidental radiologic finding. There are few cases in the literature describing the symptomatic form of the condition, known as Chilaiditi syndrome. In some cases, it may be accompanied by various severe complications. If symptoms are present, usually conservative treatment is given. However, conservative treatment only addresses the symptoms but does not prevent their recurrence and possible complications. Our present report shows that this anomaly may not only cause symptoms, but may also progress and cause severe complications, in our case—megacolon leading to right heart failure and, ultimately, death. To date, however, there have been no literature reports of death caused by colonic interposition. Therefore, it is important to draw attention to the importance of this anomaly and its appropriate diagnosis and treatment to ensure the most favorable patient outcomes.

Diagnosis, treatment, and outcomes of encapsulated papillary carcinoma: a single institution experience

Background. Encapsulated papillary carcinoma (EPC) is a rare entity of breast cancer accounting for approximately 1–2% of all breast tumours. There are no evidence-based guidelines for the treatment of EPC. Materials and methods. From the database of the National Centre of Pathology (NCP), we obtained pathology reports of 19 patients with histologically confirmed EPC, who were treated at the National Cancer Institute (NCI) in Vilnius, Lithuania, between July 2009 and July 2015. Demographic, diagnostic and treatment data were collected from medical records retrospectively. Results. During the indicated period, 19 patients with EPC were treated at the NCI. Three of them had pure EPC, they were 74 to 81 years of age at the time of diagnosis (mean 76.7 years, median 75 years); all of them are still alive and no disease progression has been observed. Seven patients had EPC associated with carcinoma in situ. Nine patients had EPC associated with invasive breast ductal carcinoma. All patients underwent surgery, in most cases – wide local excision. Only one patient died. Conclusions. EPC is a rare form of breast cancer and usually presents with an invasive breast carcinoma or carcinoma in situ in postmenopausal women. Tumours have an excellent prognosis in the cases of pure EPC and in both EPC associated with carcinoma in situ (CIS) and invasive carcinoma.

Quantitative histopathological assessment of ocular surface squamous neoplasia using digital image analysis

The aim of this retrospective pilot study was to evaluate the Aperio nuclear V9 algorithm as an image analysis tool to observe the histopathological changes of ocular surface squamous neoplasia (OSSN). A histopathological assessment, including the Ki-67 proliferative index (PI) of immunohistochemically-stained tumor conjunctiva (TC) and healthy conjunctiva (HC) tissues, was performed in six cases of OSSN. The Aperio V9 algorithm was applied to digital images of the tissue specimens to count the Ki-67 PI and to measure the nuclear area indices. This digital algorithm was validated using stereological and visual analysis methods. The visual scoring of Ki-67 PI ranged from 22 to 60% (mean, 38.5%), and from 5 to 20% (mean 9.5%) in TC and HC tissue, respectively. The computer-aided analysis, using the Aperio nuclear V9 algorithm, revealed that the Ki-67 PI ranged from 21.5 to 43.5% (mean, 33.6%), and from 1.9 to 21.0% (mean, 11.8%) in the TC and HC tissue, respectively. The stereological method demonstrated that the Ki-67 PI ranged from 30.1 to 51.5% (mean, 41.0%), and from 3.2 to 30.1% (mean, 15.1%) in the TC and HC tissues, respectively. The strongest association in the collinearity of regression analysis was observed between the Aperio nuclear V9 algorithm/stereological models in the TC tissue (r2=0.7; P=0.04) and the HC tissue (r2=0.7; P=0.03), and the visual/stereological models in the TC tissue (r2=0.7; P=0.04) and the visual/Aperio nuclear V9 algorithm models in the HC tissue (r2=0.7; P=0.04). A weak and statistically insignificant association was identified between the visual/Aperio nuclear V9 algorithm analysis in the TC tissue (r2=0.4; P=0.2) and the visual/stereological models in the HC tissue (r2=0.5; P=0.13). No significant difference was observed between the nuclear area of the TC (mean, 36.5 μm2) and HC (mean, 35.7 μm2; P=0.88) tissues. It was concluded that the Aperio nuclear V9 algorithm is a useful tool for the reliable analysis of histopathological changes of OSSN. The results of this computer-aided algorithm correlate strongly with the stereological method when assessing the Ki-67 PI.