Person:

Freeman, Michael R.

Background: Gastrointestinal stromal tumors (GIST) exhibit an unpredictable clinical course and can rapidly progress to lethality. Predictions about the biological behavior of GIST are based on a number of canonical clinical and pathologic parameters whose validity in distinguishing between a benign and a malignant tumour is still imperfect. The aim of our study was to investigate the role of morphologic parameters and expression of cells cycle regulators as prognosticators in GIST. Methods: We performed an immunohistochemical analysis for Ki67, (p27^{Kip1}), Jab1, and Skp2, on a Tissue Microarray (TMA) containing 94 GIST. Expression of the above proteins was correlated to classically used prognosticators, as well as to risk groups. Clinical significance of histologic and immunohistochemical features were evaluated in 59 patients for whom follow-up information was available. Results: Overexpression of Ki67 and Skp2, and (p27^{Kip1}) loss directly correlated with the high risk group (p = 0.03 for Ki67 and Skp2, p = 0.05 for (p27^{Kip1})). Jab1 expression did not exhibit correlation with risk. In 59 cases provided with clinical follow-up, high cellularity, presence of necrosis, and Ki67 overexpression were predictive of a reduced overall survival in a univariate model. The same parameters, as well as mitotic rate, tumour size, and (p27^{Kip1}) loss were indicative of a shortened relapse free survival interval. High cellularity, and high mitotic rate retained their prognostic significance by multivariate analysis. Conclusion: Our data suggest that a number of histologic parameters in combination with immunohistochemical expression of cell cycle regulators can facilitate risk categorization and predict biologic behavior in GIST. Importantly this study demonstrates, for the first time, that Skp2 expression correlates with Ki67 expression and high risk in GIST.

Urology holds the most enviable position in the medical firmament. Unique among specialties in bringing the surgeon in contact with humans throughout the spectrum of human life—from newborn to geriatric patients—urologists need to be adept at both medical and surgical therapies alike. In this context, drug delivery in urology has had a long, and sometimes far from illustrious, history. Traditionally, many genitourinary conditions have been treated with medications administered orally, which requires larger doses, with the concomitant side effects.