EH 1_2016

EUROPEAN HOSPITAL  Vol 25 Issue 1/16 34 PATHOLOGY Born and educated in Graz, Austria, Professor Sigurd F Lax MD established the Institute of Pathology at Landeskrankenhaus Graz Süd-West (Austria) in 2002 and today is still its head. Since 2004 he has also served as Speaker (Chair) of the Working Group on Gynaecological and Breast Pathology of the German Society of Pathology. In 2013-14 he was President of the Austrian Society of Pathology – Austrian section of IAP (ÖGPath /IAP Austria). He is a member of several national and international professional societies, including the American Association for Cancer Research (AACR) and the International Society of Breast Pathology. Authorship includes around 135 research articles and contributions in 25 books. Revealing cancer at a minuscule level Can cancer be contagious? Report: Michael Krassnitzer Since the introduction of targeted therapies in oncology the task of the pathologist has expanded beyond histological diagnostics: today, the pathologist analyses tumour tissue samples to establish a molecular profile with tumour cell character- istics – which in turn become the targets of medication. This proce- dure lays the foundation for breast cancer therapy, explained Professor Sigurd Lax, Director of the Institute of Pathology at Landeskrankenhaus Graz Süd-West (Austria), prior to the autumn congress of the Austrian Society of Pathology – Austrian sec- tion of IAP (ÖGPath /IAP Austria): ‘Pathology plays a crucial and indis- pensable role in the diagnosis, early detection and interdisciplinary ther- apy management of breast cancer,’ he pointed out. ‘The definitive diag- nosis of breast cancer and its pre- cancerous stages is established by pathologists.’ The usual procedure If suspicious lesions are detected in a radiological study, a biopsy is per- formed to collect tissue samples. ‘In more than 95 percent of cases, the pathologist can provide a conclu- sive diagnosis on the basis of those samples,’ Professor Lax points out. Interview: Sascha Keutel ‘Cancer is a genetic disease and the result of an accumulation of genet- ic changes in our cells,’ explained pathologist Professor Gieri Cathomas, when asked how cancer devel- ops and what role pathogens play. ‘Infections are involved in about 15 percent of all tumours that develop – with significant regional differences. The most important pathogens are viruses, such as the human papil- loma virus that can cause cervical cancer or the hepatitis B and C viruses that cause chronic liver infec- tion. Moreover, there are certain bacteria and parasites that play a role in tumour development. However, in most cases a viral infection alone won’t trigger cancer and fortunately most people who do get infected won’t develop a tumour. It is only a long-term infection that may lead to genetic changes that then cause tis- sue degeneration.’ Infection-associated tumours? Could cancer be contagious? ‘Cancer is not a contagious disease. Thus a person who cares for a can- cer patient won’t ‘catch’ the disease. The cancer, as such, is not conta- gious. This has to do with the fact that the viruses in the tumours have undergone changes and cannot pro- liferate. However, pathogens, like all infectious agents, are transmissible. Therefore we may indeed call certain tumours infectious.’ Which pathogen pathways and mechanisms could trigger cancer development? ‘Sexual transmission and transmis- sion by blood products are the two most frequent viral pathways, but certain pathogens can also spread by everyday human contact. In an infected human the infection has to last very long, and most of the time our immune system keeps infectious agents from taking hold. In a per- sistent infection, viral genes interact with cell genes, to be precise: the genes that regulate cell proliferation are activated or deactivated. This causes genetic instability of the cell, which in turn triggers an accumula- tion of genetic changes that lead to the development of cancer. Another mechanism is a chronic inflamma- tion caused by the pathogen, such as chronic liver inflammation after a hepatitis B and C infection. These chronic inflammations frequently lead to the damage and loss of liver cells. Consequently, new cells have to be produced incessantly and at a sometimes enormous speed which leads to genetic defects and tumours.’ How do we benefit from knowl- edge about infection-associated tumours? ‘This knowledge helps us with regard to prevention, early detection, diagnosis and therapy of pathogen- associated tumours. Let’s take the human papilloma virus in cervical cancer. The so-called Pap test is a very sensitive test for the early detec- tion of cervical cancer. ‘Prevention is the best therapy – that saying also holds true for tumours. If the cause, such as a virus infection, is known, it can be pre- vented by vaccination, as has been show in vaccination against hepatitis b and human papilloma virus. A further – individual – strategy to pre- vent infectious tumours is personal hygiene, particularly with regard to sexual intercourse, such as safe sex. This helps each of us to reduce the risk of such tumours.’ You mentioned viral infections as tumour triggers, what about bacteria? ‘Bacteria are a more complex issue. Every human being is colonised by many, many bacteria, be it on the skin, the mucous membranes, or in the intestinal tract. There are more bacteria in our colon than cells in our body. These colon bacteria, however, are highly desirable ‘residents’ since they contribute to our health. Other bacteria are ‘undesirables’ since they can cause acute and chronic diseases. Point in case: helicobacter colonises the stomach. During an infection tis- sue can be damaged and needs to be regenerated. As with the production of liver cells mentioned before this continuous and rapid process may cause a genetic instability, which triggers increased cell growth and a degeneration.’ In your crystal ball – what do you see happening over coming years in terms of pathogen-associated tumours? ‘Vaccination is a very efficient and long-term method to prevent infec- tion-induced cancer, as can be seen in the case of papilloma virus and cervical cancer or hepatitis B virus and liver cell carcinoma. I do hope that further vaccines, for example against hepatitis C or helicobacter, will be developed. ‘Another possibility is targeted therapy aiming at the pathogen itself. Moreover, highly sensitive digital systems check the biopsied lesion samples for the molecular biomark- ers oestrogen and progesterone receptors, as well as human epider- mal growth receptor 2, the so-called HER2/neu. Procedure results define the further diagnostic or therapeutic path: • A majority of breast lesions con- tain oestrogen resp. progester- one receptors and show slow or moderate growth. Most of these so-called luminal A tumours are surgically removed.  • Luminal B tumours are hor- mone receptor positive with an increased growth rate; they usu- ally respond better to chemo- therapy. • 15 to 20% of tumours are HER2 positive; medication treatment targeting HER2/neu is available.  • Triple-negative (also called basal-like) breast cancer con- tains neither oestrogen and pro- gesterone receptors, nor HER2/ neu; they grow rapidly and are very aggressive. Prior to surgery, patients with HER2 positive and triple negative carcinoma usually undergo chemo- therapy, which completely destroys the cancer cells in up to 66 percent of all cases. After surgery, the pathologist anal- yses the removed tumour bed tissue to determine therapy has been suc- cessful and prepares a report pro- viding data on tumour type, histo- pathological differentiation, tumour stage and resection margin status. In addition, the resection sample is checked again for oestrogen and progesterone receptors and HER/ neu, as well as Ki67, a tumour growth marker. The results of these histological studies inform the adjuvant therapy – either hormone therapy, targeted radiation therapy, chemotherapy or anti-HER2/neu therapy.  ‘In the past 15 years molecular tests were developed that allow us to determine a broad range of molecular changes in tumour tis- sues,’ Lax reported. While these tests cannot predict tumour response to a specific therapy, they do have a certain prognostic value, albeit, he said, ‘due to the high costs, their use is still very limited.’ Such a molecular test is Endopredict, which provides infor- mation on the probability of tumour recurrence at the original site in hormone receptor positive HER2/ neu negative patients. Lax expects to see ‘new therapy targets that promise higher survival rates spe- cifically for patients with HER2/neu negative tumours.’ In the future, Lax is sure his discipline will contribute essential knowledge to cancer therapy: ‘The success of a targeted therapy will rely to a large extent on high quality molecular pathology studies.’ Analysing tumour tissue to establish a molecular profile with tumour cell characteristics Triggers that could cause tumours Histopathologic image from ductal cell carcinoma in situ (DCIS) of the breast. No self-respecting TV crime series is without a pathologist – but the fictitious pathologist who incessantly solves crimes has little to do with reality. ‘More than 95 percent of our time is dedicated to living peo- ple,’ explains Professor Gieri Cathomas, Medical Director of the Institute of Pathology at Kantonsspital Baselland, Switzerland. Today, pathology is a clinical pillar of tumour management, from diagnosis through to therapy decisions to prognosis. But the specialty is not only tumours: ‘It’s important to men- tion that pathology also deals with infectious diseases,’ the professor adds. ‘We can contribute significant knowledge on the role of pathogens in general human diseases, including tumour development.’ a) Histology of severe epithelial dysplasia (carcin- oma in situ) of the covering cervical epithelium, the precursor lesion of cervical cancer. Epithelial architecture is abnormal, cell nuclei are enlarged and ascending mitotic figures (arrows) are present. Since the basement membrane (**) is still intact, the carcinoma is not yet invasive. In comparison b): Properly maturing cervical squamous epithelium. c) Detection of papilloma virus DNA with PCR (chromogram, arrow points at the positive peak).

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