Sebo, Thomas J.

Abstract Alterations in nuclear structure distinguish cancer cells from noncancer cells. These nuclear alterations can be translated into quantifiable features by digital image analysis in a process known as quantitative nuclear morphometry. Recently, quantitative nuclear morphometry has been shown to predict metastasis and biochemical recurrence of prostate cancer. However, little is known about the cellular mechanisms underlying these nuclear morphometric changes. Alterations of nuclear matrix proteins are frequently involved in changes of nuclear structure. A number of co-activators interact with these nuclear structure–related proteins, suggesting that they might be involved in quantitative nuclear morphometry changes. We have shown previously that the transcriptional co-activator p300 is involved in prostate cancer progression. However, the ability of a transcriptional regulator like p300 to modulate nuclear morphology has not been described previously. In the present study, we show that p300 expression in prostate cancer biopsy tissue from 95 patients correlates with quantifiable nuclear alterations. Moreover, we show that transfection of p300 into prostate cancer cells in culture induces quantifiable nuclear alterations, such as diameter, perimeter, and absorbance among others, as assessed by digital image analysis. These alterations correlate individually with aggressive features in prostate cancer, such as expression of the proliferation marker Ki-67 and extraprostatic extension of the tumor. Finally, we found that transfection of p300 into prostate cancer cells specifically increases mRNA and protein levels of nuclear matrix peptides lamins A and C, suggesting that these proteins mediate the p300-induced effects. These findings reveal a new insight into the transcriptional and structural regulation of prostate cancer.

SummaryObjectiveTo report the prevalence of parathyroid carcinoma (PC) in patients with multiple endocrine neoplasia type 1 (MEN1) and review of the literature.BackgroundPrimary hyperparathyroidism (PHP) is the most common manifestation of MEN1. The occurrence of PC in patients with MEN1 is rare and the literature regarding the clinical manifestations – including the prevalence of the disease – is scarce.ContextSingle tertiary care centre experience from 1977 to 2013.DesignElectronic search of the medical records to identify a cohort of patients with MEN1. Literature review based on current case reports.PatientsSingle case of PC in a cohort of 348 patients with MEN1. Ten cases of PC in patients with MEN1 reported in the literature.MeasurementClinical features of PC in patients with MEN1.ResultsThe prevalence of PC in 348 patients with MEN1 was found to be 0·28% (95% CI, 0–1·4%). Based on the current published cases of PC in patients with MEN1, 54·5% were women, mean age at diagnosis was 48·3 years, and the serum PTH concentrations at least four times the upper limit of the reference range in 73% of the cases.ConclusionPC in patients with MEN 1 is rare with a prevalence of 0·28%, and the clinical features are similar to PC in patients without MEN1.

AbstractBackgroundNeuroblastomas and ganglioneuroblastomas (NB/GNB) are malignant tumors that rarely occur in adults. Their disease progression and appropriate treatment are unclear.MethodsAll adults (age ≥18 years) were evaluated for histologically confirmed NB/GNB within our institution. Data were collected via chart review and direct patient contact.ResultsFrom 1980 to 2009, a total of 15 adult patients with NB/GNB were evaluated: six men (mean age 23 years, range 19–33 years) and nine women (mean 34 years, range 20–66 years). Their overall average age at diagnosis was 30 years. Tumor‐related symptoms occurred in ten patients: Pain (abdominal 3, back 2, pelvic 1, groin 1) was more common than a mass (abdominal 2) or dysmenorrhea (1). Five patients had tumors found incidentally by computed tomography (4) or chest radiography (1). Primary tumor origins were in the pelvis (4), mediastinum (3), abdomen (2), adrenal gland (2), retroperitoneum (2), and mixed locations (2). Altogether, 12 patients underwent surgical resection (biopsy in 3; resections of R0 in 5, R1 in 3, R2 in 4). Ten underwent chemotherapy. Histology showed four GNBs and 11 NBs. Five patients with stage I disease survived a mean of 21 years (range 10–40 years). Two are alive today. Three stage III patients died at 2, 6, and 9 years after diagnosis (mean 5.7 years). Six of seven patients (one was lost to follow‐up) with initial stage IV neuroblastoma died within 5 years (mean 2.7 years). NB and GNB patients had similar survivals.ConclusionsAdult‐onset NB/GNB is rare. Symptoms appear to occur later when incurable stage IV disease is detected. Complete surgical resection can lead to long‐term, disease‐free survival in stage I patients.