Alan Porter

Mammographic and ultrasound features of invasive lobular carcinoma of the breast

Invasive lobular cancer (ILC) is an important contributor to false negative mammography. This study aims to assess the value of digital mammography and to identify imaging features that could assist the radiologist to suggest the diagnosis of ILC prior to biopsy.

An epithelial to mesenchymal transition programme does not usually drive the phenotype of invasive lobular carcinomas

Epithelial to mesenchymal transition (EMT) is a cellular phenotype switching phenomenon which occurs during normal development and is proposed to promote tumour cell invasive capabilities during tumour progression. Invasive lobular carcinoma (ILC) is a histological special type of breast cancer with a peculiar aetiology – the tumour cells display an invasive growth pattern, with detached, single cells or single files of cells, and a canonical feature is the loss of E‐cadherin expression. These characteristics are indicative of an EMT or at the very least that they represent some plasticity between phenotypes. While some gene expression profiling data support this view, the tumour cells remain epithelial and limited immunohistochemistry data suggest that EMT markers may not feature prominently in ILC. We assessed the expression of a panel of EMT markers (fibronectin, vimentin, N‐cadherin, smooth muscle actin, osteonectin, Snail, Twist) in 148 ILCs and performed a meta‐analysis of publically available molecular data from 154 ILCs. Three out of 148 (2%) ILCs demonstrated an early and coordinated alteration of multiple EMT markers (down‐regulation of E‐cadherin, nuclear TWIST, and up‐regulation of vimentin, osteonectin, and smooth muscle actin). However, the data overall do not support a role for EMT in defining the phenotypic peculiarities of the majority of ILCs. Copyright

Mixed ductal-lobular carcinomas: evidence for progression from ductal to lobular morphology

Mixed ductal–lobular carcinomas (MDLs) show both ductal and lobular morphology, and constitute an archetypal example of intratumoural morphological heterogeneity. The mechanisms underlying the coexistence of these different morphological entities are poorly understood, although theories include that these components either represent ‘collision’ of independent tumours or evolve from a common ancestor. We performed comprehensive clinicopathological analysis of a cohort of 82 MDLs, and found that: (1) MDLs more frequently coexist with ductal carcinoma in situ (DCIS) than with lobular carcinoma in situ (LCIS); (2) the E‐cadherin–catenin complex was normal in the ductal component in 77.6% of tumours; and (3) in the lobular component, E‐cadherin was almost always aberrantly located in the cytoplasm, in contrast to invasive lobular carcinoma (ILC), where E‐cadherin is typically absent. Comparative genomic hybridization and multiregion whole exome sequencing of four representative cases revealed that all morphologically distinct components within an individual case were clonally related. The mutations identified varied between cases; those associated with a common clonal ancestry included BRCA2, TBX3, and TP53, whereas those associated with clonal divergence included CDH1 and ESR1. Together, these data support a model in which separate morphological components of MDLs arise from a common ancestor, and lobular morphology can arise via a ductal pathway of tumour progression. In MDLs that present with LCIS and DCIS, the clonal divergence probably occurs early, and is frequently associated with complete loss of E‐cadherin expression, as in ILC, whereas, in the majority of MDLs, which present with DCIS but not LCIS, direct clonal divergence from the ductal to the lobular phenotype occurs late in tumour evolution, and is associated with aberrant expression of E‐cadherin. The mechanisms driving the phenotypic change may involve E‐cadherin–catenin complex deregulation, but are yet to be fully elucidated, as there is significant intertumoural heterogeneity, and each case may have a unique molecular mechanism.

Kerry Vincent Casey (1934-2018)

Kerry Casey was born in Sydney, the eldest of three boys but spent most of his childhood in Wagga. The family moved to Canberra when Kerry’s father took up a position with the Immigration Department and Kerry boarded at St Patrick’s Goulburn, where he excelled both academically and as an athlete. The family was transferred to London and Kerry finished his schooling in the UK. He loved music and the piano and on Australia Day 1949 at age 14, Kerry played ‘Waltzing Matilda’ on UK television for a young Julie Andrews. I believe Julie’s career blossomed after this performance. When the family moved back to Australia, Kerry enroled in Medicine at Sydney University. To support himself as a student he worked nights as a taxi driver around the inner city, experiencing a side of life from which he had been previously sheltered. Prior to graduation, he met and married young midwife Noelene and they moved to Brisbane where Kerry worked as a Resident at Princess Alexandra Hospital, later commencing training in Radiology. He was the rock that kept the department together, always cheerful and willing to help his clinical colleagues. He held various staff positions at the hospital, including Acting Director and later was a member of the visiting staff. In the late 1960s, Kerry was invited to join Harry, John and Les Masel’s quality practice on Wickham Terrace, forming the partnership Masel and Casey, later becoming part of what is now Queensland Diagnostic Imaging. Kerry’s skill, charisma and management style contributed enormously to the success of the practice. He also enjoyed his involvement in the Army for many years and was a consultant Radiologist, rising to the rank of Lieutenant Colonel. Kerry excelled technically and performed admirably in Angiography and Lymphography or changing the gear box in his beloved Land Rover. He was a man of many talents and he could fix anything; he was an excellent home handyman, hair dresser for his children when they were young, he even sewed the curtains in their home. Kerry was also a very humble, gentle, kind and generous man. He loved to laugh and it was always a joy to be in his company. Kerry dearly loved his family – he was a devoted husband, father and grandfather. As well as his love of family, Kerry loved fishing. The annual trip to Fraser Island in August took months of preparation and was a highlight in his year. With his Chief Radiographer mate Allan Towner and other friends, enough fish were often caught to feed his large family for weeks. Kerry’s love of Fraser Island and fishing is continued by his family. Kerry is deeply missed by his loving family – his wife Noelene, their six children, seventeen grandchildren and three great grandchildren. Our College has lost a Life Member and dedicated practitioner of our speciality.

Full-field digital mammography: Is the apparent increased detection of microcalcification leading to over-investigation and over-diagnosis?

Modern full‐field digital mammography (FFDM) appears to have increased the detection of breast microcalcification. This retrospective study aimed to assess whether this is associated with over‐investigation and possible over‐diagnosis of breast pathology of lesser significance.

Frederick Schubert BSc, MBBS, FRACR, FRCR, BA, DDU (1926-2017)

Frederick Schubert was born in 1926 in his grandfather’s house in the inner Brisbane city suburb of Spring Hill. He died peacefully on the 18th of April 2017. Fred was the son of a railway engine driver, Wilhelm Schubert. From this humble background, he rose to become the 40th President of our College. He did this through the sheer force of his personality; through his academic brilliance, and through his dedication over an entire lifetime not just to learning for its own sake, but especially to learning and sharing his knowledge of the science and art of radiology. My father was a family friend of the Schuberts, and I first met Fred when I was 6 years old. He was then in his late teens and I used to see him sitting on the front steps of his family’s old railway house, a house ‘on stilts’ opposite the Mayne Junction Railway goods yards. I recall one occasion when he came with us on a visit to Redcliffe. A boy ran out in front of our car and we bumped him. Fortunately, he was not badly hurt, and Fred volunteered to run down to the shop with a sixpence to buy him an icecream. Meanwhile the boy’s father had emerged from his house and clipped his son’s ears for running onto the road! We dutifully went down to the Police station to report the incident, but it was Saturday and the Sergeant was drunk, so that mission proved abortive. Fred loved telling this story as an illustration of how times have changed, but I like to think of it as an early example of Fred’s ability to cope and to care – on that occasion for the first of the many casualties that he was to come across and help in his professional life. After attending The Fortitude Valley State Primary School, Fred enrolled at St Joseph’s College, Gregory Terrace. He excelled academically, but still found time to captain the College’s first cricket XI and be the Vice-Captain of the rugby First XV. He was one of only 20 students in the State to earn an Open Scholarship to the University of Queensland, where he initially graduated in Science. He became a ferocious hockey player and won a University Blue, only narrowly missing out on a Rhodes Scholarship for his combination of academic and sporting prowess. Fred subsequently enrolled in Medicine, graduating in 1951, and commenced training as a radiologist at what is now the Royal Brisbane and Women’s Hospital (formerly the BGH). He completed his training at the Royal Melbourne Hospital under the legendary Dr Barbara Wood. This was indeed a tough finishing school but his Christian Brothers education had accustomed Fred to a high degree of discipline and hard endeavour. He duly became a Member of the College in 1957. A few years later my father met Fred once more, and told him that I had just graduated in medicine. There is a famous moment in the movie ‘The Graduate’ where Dustin Hoffman is told by a family friend, in one word, what his

Abstract P1-07-08: Mixed ductal-lobular carcinomas of the breast: Abrogated cell adhesion in the clonal evolution from ductal to lobular morphology

Mixed ductal-lobular carcinomas (MDL) display both ductal and lobular morphology, and are a clear example of intratumour morphological heterogeneity. The evolution of MDL carcinomas is not well understood. There is a paucity of data surrounding the genetic origin of the different morphological compartments and it remains to be seen whether the coincident presentation of these distinct morphological entities represents two independent tumours that have collided (so called 9collision tumours9), or whether they arise from a common clone. We propose that clonal progression during the evolution of these tumours is associated with a change in phenotype. To address this, a cohort of 82 MDLs was studied for clinical, morphological and molecular features. Key findings include: i) MDLs more frequently co-exist with ductal carcinoma in situ (DCIS) than lobular carcinoma in situ (LCIS); ii) the E-cadherin-catenin complex was recurrently normal in the ductal component but aberrantly localised in the lobular component of the same tumour; iii) E-cadherin deregulation in the lobular component was almost always aberrantly located to the cytoplasm, conversely classic ILCs are typically completely negative for this molecule; iv) epithelial to mesenchymal transition marker expression was not associated with E-cadherin deregulation. Comparative Genomic Hybridsation (CGH) and exome sequencing was performed to investigate clonal relationships between the different intratumour morphologies and identify mechanisms underlying the change in phenotype. Our analysis revealed that i) all morphological components within a case are clonally related; ii) divergence of the morphological components may occur early during tumour evolution (where both DCIS and LCIS are present) or later during tumour progression (cases with only DCIS detectible); and iii) mutations were identified in genes such as CDH1 and ESR1 , and other breast cancer driver genes. Together, these data strongly support the concept that the disparate morphological components of these mixed tumours are clonally related, and are not the result of a collision event. Furthermore, we show that lobular morphology can arise via a 9ductal9 pathway of tumour progression. The mechanisms driving the change in phenotype are yet to be fully elucidated, but there is significant intertumour heterogeneity and each case may utilise a unique molecular mechanism. Citation Format: McCart Reed AE, Kutasovic JR, Nones K, da Silva L, Melville L, Jayanthan J, Vargas AC, Reid LE, Saunus JM, Cummings MM, Porter A, Evans E, Waddell N, Lakhani SR, Simpson PT. Mixed ductal-lobular carcinomas of the breast: Abrogated cell adhesion in the clonal evolution from ductal to lobular morphology [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-07-08.

The role of epithelial to mesenchymal plasticity in driving the invasive capacity of 'lobular-like' tumour cell differentiation in breast cancer

15th International Biennial Congress of the METASTASIS RESEARCH SOCIETY Heidelberg, Germany, June 28th–July 1st, 2014 Springer Science+Business Media Dordrecht 2015