لخّصلي

In a series of publications on gliomas, Hans-Joachim Scherer (1906-1945), a young German neuropathologist working in exile at the Institut Bunge (Antwerp, Belgium) was decades ahead of his contemporaries in his insight into the pathology and biology of brain tumors (2).The distinction between primary and secondary glioblastomas was a remarkable observation at that time.

In a series of publications on gliomas, Hans-Joachim Scherer (1906–1945), a young German neuropathologist working in exile at the Institut Bunge (Antwerp, Belgium) was decades ahead of his contemporaries in his insight into the pathology and biology of brain tumors (2). The distinction between primary and secondary glioblastomas was a remarkable observation at that time. In the first edition of the World Health Organization (WHO) Classification of Tumors of the Nervous System, published 40 years later, glioblastomas were not even recognized as astrocytic neoplasms but listed in a group of “poorly differentiated and embryonal tumors” (3). Only after the introduction of immunohistochemistry was their astrocytic origin unequivocally established (4). Although it was recognized in clinical practice that some glioblastomas developed after resection of low-grade or anaplastic astrocytomas, Scherer's distinction remained conceptual as histopathologically these subtypes could not reliably be distinguished.
In 1996, we reported evidence that primary and secondary glioblastomas carry distinct genetic alterations (5). TP53 mutations were found to be uncommon in primary glioblastomas but occurred with a high incidence in secondary glioblastomas; EGF receptor (EGFR) overexpression prevailed in primary glioblastomas but was rare in secondary glioblastomas. Only 1 of 49 glioblastomas showed TP53 mutation and EGFR overexpression, indicating that these alterations are mutually exclusive events defining 2 different genetic pathways in the evolution of glioblastoma (5). Subsequently, many studies provided evidence that primary and secondary glioblastomas develop through distinct genetic pathways (6, 7). Typical for primary glioblastomas are EGFR amplification, PTEN mutation, and entire loss of chromosome 10 (6–8). Genetic alterations more common in secondary glioblastomas include TP53 mutations and 19q loss (6, 7, 9). However, until the identification of IDH1 mutation as a molecular marker of secondary glioblastoma (10–13), the patterns of genetic alterations, though different, did not allow an unequivocal separation of the 2 subtypes.