The role of PTEN tumor suppressor pathway staining in carcinoma in situ of the bladder

ObjectivesThe PI3k/Akt pathway has been associated with the development and progression of bladder tumors, with most studies focused on papillary or muscle-invasive tumors. We sought to characterize the expression patterns of the PI3K/Akt pathway in a large cohort of high-risk preinvasive carcinoma in situ (CIS) tumors of the bladder. Our goal was to understand whether PI3K/Akt pathway alterations associated with CIS resemble early- or late-stage bladder cancers.Material and methodsWe evaluated tissue specimens from 97 patients with CIS of the bladder, of which 14 had a concomitant papillary tumor. All patients were treated with intravesical bacillus Calmette-Guerin. All specimens were evaluated for PTEN, p-AKT, and p-S6 immunoreactivity. Markers were evaluated for percentage and intensity of staining and were scored using a 0 to 3+grading system.ResultsPTEN staining was noted as least intense in 67% of tumor specimens and 22% of normal urothelium. P-Akt and p-S6 had intense staining in 77% and 90% of tumor specimens vs. 44% and 68% in normal tissue, respectively. Low-intensity staining for PTEN at 12 months correlated with higher recurrence risk (P = 0.026).ConclusionWe describe a large cohort of CIS bladder tumors with decreased staining intensity of PTEN and increased staining intensity of p-AKT and p-S6, similar to high-grade and high-stage papillary tumors. Low-intensity staining of PTEN at 12 months was associated with an increased risk of recurrence.     

Granular cell tumor of the breast: a series of 17 cases and review of the literature

Seventeen cases of granular cell tumor (GCT) of the breast are reviewed. The demographics and clinical features are reviewed and the radiologic and pathologic features as well as the immunohistochemistry are discussed. To our knowledge, our series of 17 breast GCT cases represent the largest series published to date.     

Lentiviral-Induced High-Grade Gliomas in Rats: The Effects of PDGFB,HRAS-G12V,AKT, and IDH1-R132H

In human gliomas, the RTK/RAS/PI(3)K signaling pathway is nearly always altered. We present a model of experimental gliomagenesis that elucidates the contributions of genes involved in this pathway (PDGF-B ligand, HRAS-G12V, and AKT). We also examine the effect on gliomagenesis by the potential modifier gene, IDH1-R132H. Injections of lentiviral-encoded oncogenes induce de novo gliomas of varying penetrance, tumor progression, and histological grade depending on the specific oncogenes used. Our model mimics hallmark histological structures of high-grade glioma, such as pseudopalisades, glomeruloid microvascular proliferation, and diffuse tumor invasion. We use our model of gliomagenesis to test the efficacy of an experimental brain tumor gene therapy. Our model allowed us to test the contributions of oncogenes in the RTK/RAS/PI(3)K pathway, and their potential modification by over-expression of mutated IDH1, in glioma development and progression in rats. Our model constitutes a clinically relevant system to study gliomagenesis, the effects of modifier genes, and the efficacy of experimental therapeutics.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-014-0269-y) contains supplementary material, which is available to authorized users.Key Words: Gene therapy, HSV1-TK, adenoviral vectors, brain tumors     

Prospective evaluation of plasma kinetic bipolar resection of bladder cancer: comparison to monopolar resection and pathologic findings

Objective

To determine whether the Gyrus ACMI plasma kinetic bipolar device (Gyrus ACMI, Southborough, MA) improves pathologic specimen preservation and clinical outcomes compared to standard monopolar electrocautery.

Patients and methods

In our prospective study, 83 patients underwent monopolar or bipolar transurethral resection of bladder tumors between April 2006 and February 2007 at Memorial Sloan-Kettering Cancer Center. Dedicated genitourinary oncology pathologists blinded to resection type and assessed pathologic features including stage and grade, presence of muscularis propria, fragment size, presence and thickness of thermal artifacts within the specimen, layer of tissue most affected, severity of tissue distortion, and diagnostic impact of thermal artifacts. Clinical outcomes including, perforation, obturator reflex, need for muscle paralysis, a catheter, or admission, were recorded. Clinical and pathologic outcomes between resection modality were compared.

Results

There were no significant thermal artifacts in 9/38 (23.7 %) and 11/45 (24.4 %) monopolar and bipolar specimens, respectively. The layer of bladder tissue most affected by thermal artifacts was readable in 18/38 (47.4 %) monopolar and 27/45 (60.0 %) bipolar specimens. Tissue distortion from thermal artifacts led to areas within 11/38 (28.9 %) monopolar and 7/45 (15.6 %) bipolar specimens being unreadable. Ultimately, thermal artifacts caused moderate diagnostic difficulty in 2/38 (5.3 %) specimens of the monopolar group and severe diagnostic difficulty in 1/45 (2.2 %) bipolar specimens. Clinically, there was no major difference between resection methods.

Conclusion

Plasma kinetic bipolar equipment appears to cause less tissue distortion and has the potential to facilitate staging and grading of bladder tumors. No differences in clinical outcomes were appreciated between resection methods. If these results can be repeated in larger studies, the bipolar device represents a small advancement in transurethral resection.