Dr. Marc Ladanyi is an active investigator in molecular pathology and sarcoma biology. Over the past
12 years, his research work has centered on the interface of molecular pathology and surgical
pathology, reflecting his training and board certification in both anatomic pathology and clinical
Dr. Ladanyi, a Canadian, received his M.D. in 1984 at the age of 23 from McGill University in
Montreal with the distinction of University Scholar (summa cum laude). Interestingly, the same class
produced two other active members of the academic pathology community, Poul Sorensen and Robert Odze!
Throughout medical school Dr Ladanyi planned a career in Neurology, but decided to spend a year in
Pathology after graduating in order to gain a more solid understanding of disease. As he began
Pathology training, Neurology soon lost its appeal and he committed himself to Anatomic Pathology. In
the course of his Pathology Residency at McGill his interest in the emerging field of cancer genetics
was fostered by stints in the laboratories of Serge Jothy and Tom Seemayer. In 1987 he sought to
complete his Anatomic Pathology training with a fellowship at Memorial Sloan-Kettering Cancer Center
(MSKCC) in New York City, where he then acquired additional training in Genetics and Cytogenetics,
followed by research on lymphoma translocations in the laboratory of Raju Chaganti. In 1993, he
joined the staff at MSKCC and since 1994 he has been Director of the Laboratory of Diagnostic
Molecular Pathology in the Department of Pathology.
Dr. Ladanyi has received several awards, including the College of American Pathologists Foundation
Scholar Award, an American Cancer Society (ACS) Clinical Oncology Career Development Award, the
Benjamin Castleman Award of the USCAP (1995), as well as the Boyer Award for Clinical Research at
MSKCC (2001). He is currently funded as a principal investigator on grants from the NIH (and
previously the ACS). He is particularly active as a peer reviewer, both on several journal editorial
boards and in grant review committees [NIH, ACS, MRC (Canada)]. He also functions as Associate Editor
at the Journal of Molecular Diagnostics and at the Journal of Clinical Pathology. Dr Ladanyi has
authored or co-authored over 120 research papers and more than 20 reviews or chapters and recently
co-edited with William Gerald the first book on gene expression profiling of human tumors, Expression profiling of human tumors: Diagnostic and research applications
Chromosomal translocations have been at the core of his research efforts, as this class of alterations
has provided the richest source of practical diagnostic markers as well as many important insights
into tumor biology. From the beginning of his independent research, at the encouragement of Andrew
Huvos, he has focused in particular on sarcomas with translocations. Several recurrent themes run
through his laboratory output, including translocation
breakpoint cloning, the practical application of translocation testing through RT-PCR assays or
surrogate immunohistochemical assays, the use of molecular translocation testing to clarify the
clinicopathologic spectrum of existing entities and to define new ones, the biologic and clinical
correlates of fusion gene structure, the functional aspects of fusion genes that encode chimeric
transcription factors and how they impact on cellular phenotype and gene expression profiles, and the
contrasting biology of translocation-associated sarcomas and non-translocation sarcomas with complex
karyotypes. His experimental approaches have utilized almost exclusively human tumor material and
human cancer cell lines, reflecting his view that it for this type of research that investigators with
an anatomic pathology background are uniquely qualified. In 2003, he was selected to be a member of
the Sarcoma Progress Review Group convened to advise the National Cancer Institute on future sarcoma
In the area of translocation breakpoint cloning, his laboratory has been involved in the cloning of
several novel fusion oncogenes, including EWS-WT1, ASPL-TFE3, CLTC-TFE3, ATIC-ALK, and EWS-SP3. Detection of the EWS-WT1 fusion has become a widely used molecular diagnostic test for the
desmoplastic small round cell tumor. He and his collaborators recently established
immunohistochemistry for TFE3 as a practical diagnostic assay that can substitute for molecular
testing for ASPL-TFE3 and otherTFE3 gene
fusions in alveolar soft part sarcoma and TFE3 translocation carcinomas
of the kidney. They have more recently demonstrated that staining for TFEB can likewise be used as an
assay for the related renal carcinomas with the Alpha-TFEB translocation.
His group has also established and published RT-PCR assays for these and many other gene fusions.
In the area of biologic and clinical correlates of fusion gene structure, his laboratory demonstrated
the relationship of EWS-FLI1 fusion structure to transactivation,
proliferative rate, and survival in Ewing sarcoma, and of SYT-SSX structure to epithelial differentiation and survival in synovial sarcoma.
These findings have strengthened the notion that these gene fusions play a central role in the biology
of their respective sarcomas.
In studies more directly relevant to surgical pathology, his group has employed molecular
translocation testing to contribute to the definition, delineation, or clarification of the
clinicopathologic spectrum of numerous entities, including Ewing sarcomas, olfactory neuroblastoma,
skeletal and extraskeletal myxoid chondrosarcomas, classic myxoid/round cell liposarcoma and
predominantly myxoid well-differentiated liposarcoma, endometrial stromal neoplasms, primary renal
synovial sarcoma, and TFE3/TFEB translocation carcinomas of the kidney.
Indeed, his studies, with Pete Argani of Johns Hopkins, on renal TFE3
translocation carcinomas and renal synovial sarcomas led to their acceptance as new and distinct tumor
entities and their inclusion in the most recent WHO classification of renal tumors.
His work has also contributed to the understanding of translocation-associated sarcomas by
highlighting the special impact of p53 (and p16/CDKN2A) alterations in these tumors, their distinctive
pattern of telomere maintenance mechanisms, as well as their highly specific gene expression profiles.
He was among the first to highlight how these and other features of translocation-associated sarcomas
contrast sharply with those of non-translocation sarcomas with complex karyotypes, such as
osteosarcoma and mesothelioma, both of which have also been the subject of studies in his laboratory.
His group work in mesothelioma has shown that p16/CDKN2A homozygous
deletion, the key genetic alteration in this tumor, can be used as a diagnostic marker in pleural
effusion cytology. Their demonstration in mesotheliomas of very frequent co-deletion of MTAP, a gene adjacent to p16/CDKN2A, formed the
basis for including this cancer in a national trial of targeted chemotherapy in MTAP-deficient cancers.
Dr. Ladanyi has not shied away from controversy, having participated in responses to various
contentious PCR-based findings. In this his perspective is informed by his experience both in cancer
genetics and in the practical pitfalls of molecular diagnostics. Most recently his team debunked the
proposed association of SV40 and mesothelioma and proposed an explanation for the high risk of false
positive SV40 PCR results in the testing of this and other human tumors.
He is an active member of USCAP and the Association for Molecular Pathology and was responsible for
its application for companion society status and the organization of its inaugural companion meeting
at USCAP in 2001.
Finally, the productivity of his laboratory also reflects the quality of his valued collaborators,
such as Pete Argani, Cristina Antonescu, William Gerald, Julie Bridge, and others. His wife, Dr.
Maureen F. Zakowski is a pathology colleague at MSKCC and their nine year old daughter, Anne-Sophie,
plans to take over Dad's lab when he retires.