1. ¹Department of Pathology, Division of Anatomic Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
2. ²Division of Neuropathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
3. ³Division of Hematology Oncology, University of Pittsburgh Cancer Center, Brain Tumor Center, University of Pittsburgh, Pittsburgh, PA, USA

Correspondence: Dr D Mohan MD, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. E-mail: Deepak.Mohan@csmc.edu

^*From July 2004 is with the Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Received 22 January 2004; Revised 7 April 2004; Accepted 7 April 2004; Published online 4 June 2004.

Abstract

Molecular anatomic pathology represents the blend of traditional morphological methods and the multigene approach to determine cancer-related gene alterations for diagnostic and prognostic purposes. Microdissection genotyping was utilized to characterize 197 gliomas with targeted microdissection of 2–7 areas spanning the spectrum of histologic types and grades. The methodology described herein is complementary to the existing realities of pathology practice. The technique utilizes paraffin-embedded fixative-treated tissue of small sample size after the primary morphological examination by the pathologist. Molecular information derived from microdissection genotyping in combination with the traditional histological information, results in an enhanced understanding of glioma formation and biological progression leading to improvements in diagnosis and prediction of prognosis. In all, 100% or 32 of 32 cases with at least partial treatment response was observed in neoplasms possessing the 1p or 1p/19q loss. The 19q loss alone without coexisting 1p showed no improvement in treatment response. Gliomas lacking 1p loss with only allelic loss involving 3p, 5q, 9p, 10q and 17p showed unfavorable outcome of only 35%, or six of 17 cases with treatment response. In addition, the determination of fractional allelic loss (favorable/unfavorable), was a very good independent predictor of biological behavior. These findings emphasize the importance of determining the cumulative pattern of mutational damage on 16 distinct sites or more, especially in the presence of 1p loss which in isolation or in combination with 19q is a favorable prognostic factor for therapeutic response.