I have been asked to say a few words about this gentle and eccentric man who introduced me to iPods, Harry Potter and importantly, colorectal polyps. In November 2008, Jeremy Jass passed away just over a year after he was diagnosed with glioblastomamultiforme. During his illness he was calm resigned and brave, and he never expressed a word of bitterness that life had dealt him this terrible blow. He was just 57 years old.
For those who did not know him, Jeremy was a brilliant and innovative world-class colorectal pathologist who contributed enormously to our understanding of familial CRC. For well over two decades, he produced important and original work in the form of over 300 papers including 50 reviews, over 50 books and book chapters, and countless lectures to both students and conference audiences all over the world. He was awarded many prizes including the Goudie Medal in 2007.
One of the things you quickly notice when you look back over Jeremy’s work is that if there was anything really important to know about colorectal cancer, he was all over it.
In 1988, Jeremy accepted the position of Professor of Pathology in Auckland, NZ, where he stayed for 8 years
This is the family Jeremy reported in 1996. A mother had CRC at 34 and 5 of her 10 children had CRC some with multiple serrated polyps, these were also present in the grandchildren. The level of MSI was variable
On the morning Jeremy arrived at his new job in Brisbane in 1996, he called me and said “I have 3 papers to show you, and funding to start a research program. Let’s see what we can do.” It was one of life’s pivotal moments; from that day on, going to work became an adventure. Every day we would scan the literature. I had never met anyone who could generate hypotheses so far ahead of current thinking, and who could hold up a H&E slide to the light streaming in the windows and tell you that it was a Lynch syndrome cancer without the benefit of a microscope. These three papers demonstrate how insightful Jeremy was; in 1983 (25 years ago), this paper challenged the dogma that hyperplastic polyps were of no consequenceThe second paper suggests that clinical criteria alone over-diagnose Lynch syndrome, and that there is a significant portion of familial CRC remaining unexplainedThe third paper is the first description of a serrated neoplasia family, a novel condition distinct from Lynch syndrome which we call Jass syndrome
The serrated pathway continued apace with more molecular evidence in the form of mucin profiling and BRAF mutation
What sort of cake would be baked for Jeremy’s farewell party? With multiple sessile polyps and the serrated pathway signature of synchronous proximal cancers
Completing the circle…
Many of us have much to thank him for; he opened door for us, and he opened our minds to new possibilities.Many of us would also agree that we miss his counsel, his wit, his legendary puns, and his ability to see clearly through complex and even counterintuitive data.
Jeremy’s insights into the mechanisms of colorectal neoplasia will continue to illuminate our working lives for many years to come. Chief among them is the concept that colorectal cancer is a heterogeneous group of conditions, that it can be divided into groups with clinical relevance based on molecular features, and importantly, both clinical and research approaches should consider it in this light. Throughout his career, he enriched our understanding of colorectal cancer by encouraging this view. His work on the evolution of colorectal cancer subsets has served as a basis for an expanded approach to screening, diagnosis and research, and this will live on as an important legacy. He was also a major fan of TolkienAs familial CRC becomes ever more complex, his insights will be greatly missed.
This slide shows the epitaph on Jeremy’s resting place; the emblem depicts the Ring Classification for colorectal cancer proposed by Jeremy and it is perhaps what he wishes to be remembered for. He truly was a citizen of the world.
Born 13 May 1951 UK 1972 Graduated (first class honours) BSc 1975 Graduated from Westminster Medical School. 1983 MD (London) 1994 FRCP 1996 DSc (Med) Worked as a pathologist in the UK culminating in his appointments in 1986 as Consultant Histopathologist St. Mark's Hospital Senior Lecturer St. Bartholomew's Hospital, London First paper : Management of dermatomyositis. Jass JR. Br Med J. 1978; over 300 more were to come Several papers on intestinal metaplasia in gastric cancer A paper on mucins which was one of his lifelong interests and which was to play an important part in his recognition of the serrated pathway many years later Early Career Highlights (1)
Early Career Highlights (2) Histopathology 1980 Metaplastic polyps and polyposis of the colorectum recognition of HPS as a pathological entity Cancer 1981 A comparative ultrastructural study of hyperplastic and adenomatous polyps, incidental and in association with colorectal cancer recognition of abnormalities in hyperplastic polyps associated with CRC Lancet 1983 Relation between metaplastic polyp and carcinoma of the colorectum; “To explain the functional overlap between metaplastic polyps and carcinoma, it is suggested that the two separate sets of factors which lead to the development of adenomas and metaplastic polyps are both required to bring about malignant transformation within the colorectum. Identification of the factors causing metaplastic polyp formation could therefore have important implications in the prevention of colorectal cancer.” Began to suspect hyperplastic polyps of not being an innocuous as everyone believed; continued to publish widely on GIT cancers, dysplasia and mucins Multiple Publications 1986-1988Jass Grading System for CRCs Nature 1987 Mapping of the FAP locus to 5q using allelic loss
Auckland, NZ (1988-96) 1988 Professor of Pathology University of Auckland
1992 Gut Predictors of presence, multiplicity and dysplasia of colorectal adenomas. A necropsy study in New Zealand Association between ethnicity and serrated polyps Association between hyperplastic polyps and adenomas Finding that females with adenomas were more likely to have high-grade lesions 1993 N Z Med J Establishment of a registry for hereditary nonpolyposis colorectal cancer in New Zealand importance of MSI testing, establishment of mutation testing 1993 Science Genetic mapping of a locus predisposing to human colorectal cancer (Family J was a New Zealand MSH2 family) 1993 J Mol Med Colorectal neoplasms detected colonoscopically in at-risk members of colorectal cancer families stratified by the demonstration of DNA microsatellite instability Evidence that a significant amount of familial colorectal cancer is unexplained Many papers on pathology and molecular aspects of Lynch syndrome including the nature of precursor lesions, as well as the interesting condition hereditary mixed polyposis syndrome (HMPS); the tissues have a limited repertoire of responses to genetics and environment and phenotypes can overlap Here Jeremy continued his collaborations with colleagues in the UK, as well as becoming a truly international collaborator with a prolific output of publications Jeremy in New Zealand
Familial giant hyperplasticpolyposis predisposing to colorectal cancer: a new hereditary bowel cancer syndrome J Pathol. 1996 May;179(1):20-5. Mixed epithelial polyps in association with hereditary non polyposis colorectal cancer providing and alternative pathway of cancer histogenesis Pathology. 1997 Feb;29(1):28-33. The Description of a New Syndrome of Familial CRC
1996 Professor of Pathology and Head of Anatomical Pathology, University of QLD Brisbane, AUSTRALIA 1996-2002
Jass JR (1983). Relation between metaplastic polyp and carcinoma of the colorectum. Lancet. 1(8314-5):28-30. Factors which bring about metaplastic polyps are also important in the development of colorectal cancer; 25 years ago, this paper was challenging the dogma that hyperplastic polyps were of no consequenc Jass JR, et al (1995). Diagnostic use of microsatellite instability in hereditary non-polyposis colorectal cancer. Lancet. 346(8984):1200-1. “Reliance upon clinical data alone may result in over-diagnosis of HNPCC” “The criteria could be refined by inclusion of RER status.” Jeevaratnam P, et al (1996). Familial giant hyperplasticpolyposis predisposing to colorectal cancer: a new hereditary bowel cancer syndrome. J Pathol. 179(1):20-5. Description of a NZ family fulfilling HNPCC clinical criteria in which there were MSI negative and MSI positive CRC and multiple giant hyperplastic polyps; Suggested that this represented a novel familial syndrome predisposing to colorectal cancer; It was in a single patient with hyperplasticpolyposis and 6 synchronous CRC, that Jeremy defined the serrated pathway at a molecular level 4 years later The Seeds of the Serrated Neoplasia Pathway
Continued his prolific output with wider collaborations world-wide Began to travel constantly to talk at meetings Became the PI of the Australasian Site of the Colon CFR 1999 Found that the mucin pattern of sporadic MSI-H CRC was the same as hyperplastic polyps, and that hyperplastic polyps showed low level MSI suggesting that sporadic MSI-H CRC arise in hyperplastic polyps 2000 Found that patients with hyperplasticpolyposis produced MSI-H CRC as well as MSI-L and MSS thereby demonstrating the plasticity of the serrated pathway endpoints, and showed dysplasia in areas where MLH1 was missing 2000 Formulated the serrated neoplasia pathway of CRC development at the molecular level and began to publish multiple papers explaining this mechanism 2004BRAF mutation characterised the precursor lesions of MSI-H sporadic CRC Serrated adenoma of the colorectum: a lesion with teeth. Serrated route to colorectal cancer: back street or super highway? Hyperplastic polyps of the colorectum-innocent or guilty? Jeremy in Australia
Gastroenterology 2002Emerging Concepts Paper Evidence points to a "serrated" pathway of neoplasia Driven by inhibition of apoptosis and subsequent inactivation of DNA repair genes by promoter methylation Earliest lesions in this pathway = aberrant crypt foci (ACF). ACF may develop into hyperplastic polyps or transform into admixed polyps, serrated adenomas, or traditional adenomas. Serrated pathway CRC - microsatellite status variable HyperplasticPolyposis a clinical model for this pathway
2002-2006 Montreal, CANADA 2002 Professor of Gastrointestinal Pathology, McGill University
Demonstrated that the apparently normal mucosa in hyperplasticpolyposis was heavily methylated; began work on his molecular classification system for CRC; began work on the KRAS-mutated CRC in the fusion pathway Jeremy had become an international celebrity; traveling internationally up to twice each month; in a 6 month period he once traveled 14 times outside Canada Continued prolific output, many reviews, many important papers on the molecular nature of serration (and its relation to senescence through BRAF) and the histopathlogical recognition of advanced serrated polyps Began to tire of the cold and constant travel and took up an offer to return to St Mark’s where it had all begun 22 years previously Returned to London in 2007 as Professor of GIT Pathology at Imperial College and sadly was diagnosed later that same year He passed away in London on November 30, 2008 Jeremy in Canada
Remembering Jeremy… Jass Lectures Insight Jass Lecture 2009 Dusseldorf: Richard Houlston Jass Memorial Lecture 2009 Kingscliffe, NSW: Susan Parry CGA-ICC Jass Lecture 2009 Hawaii: Loic le Marchand One day in the future, name familial serrated neoplasiaJass Syndrome in memory of the person who first described it back in 1996 Go back and read his papers; particularly prior to 2002; even the old ones have many things to teach us
Strived for excellence in his work Inspired and taught others through example Modeled a good working life Shared what he knew, contributed to the greater good Collaboration Pathologists, Gastroenterologists, Geneticists, Scientists, Surgeons, Counsellors “Chance favors the prepared mind” Read widely and sought to understand Open to new ideas Challenged dogma Sought the truth Courage to disagree Showed leadership Writing letters to journals Writing letters to colleagues Publish, even if it has to be in lower order journals; get it out there! Don’t give up Jeremy’s example…