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Morphology of Tumor Cell Nuclei Is Significantly Related with Survival Time of Patients with Glioblastomas

Departments of ¹ Neuroradiology, ² Neurosurgery, and ³ Neuropathology (Edinger Institute), Clinics of Johann Wolfgang Goethe University, Frankfurt, Germany; and ⁴ Department of Biometrics, Medical School Hannover, Hannover, Germany

Requests for reprints: Reinhold Nafe, Department of Neuroradiology, Clinics of Johann Wolfgang Goethe University, Schleusenweg 2-16, D-60528 Frankfurt am Main, Germany. Phone: 49-69-6301-5462; Fax: 49-69-6301-5989; E-mail: r.nafe{at}em.uni-frankfurt.de.

Purpose: To investigate whether histomorphology of tumor cell nuclei has a significant and independent relation to survival time of patients with glioblastomas.

Experimental Design: Seventy-two tumors from 72 patients were investigated by means of digital image analysis. Proliferating and nonproliferating nuclei were separately measured and parameters of nuclear size, shape, texture, and spatial relationships (topometric parameters) were detected. Survival analysis was done regarding morphometric data together with the patients' age, the amount of resection (total or subtotal), and the classification of the tumor as a "primary" (de novo) or "secondary" glioblastoma.

Results: The overall relation of all morphometric data to the time of survival was highly significant (Cox analysis, P < 0.0001). Apart from the extent of surgical resection, parameters of nuclear shape and topometric variables, such as the distance between two nuclei lying nearest to each other, showed an independent and significant relation to survival time. The patients' age had also a significant but comparably slight relation to survival time.

Conclusions: The morphology of tumor cell nuclei, as represented by morphometric data, shows a significant relation to survival time of patients with glioblastomas. This relation is statistically independent from the amount of surgical resection, from the patients' age and from the classification of the glioblastoma as being primary or secondary. The results support the view that histomorphometry of tumor cell nuclei is a valuable prognostic marker for patients with glioblastomas. We believe that such a marker ought to be incorporated into the formation of individual therapeutic decisions.

Key Words: Gliomas • Prognosis • Quantitative Analysis • Survival Analysis