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Current study reveals new treatment option for thyroid cancer

(Vienna, 12th July 2011) Medullary thyroid carcinoma is a variant of thyroid cancer which is extremely difficult to treat - except with surgery. Pathologists at the Medical University of Vienna have now discovered how this type of cancer spreads. This discovery has now opened up for the first time ever the possibility of treating medullary thyroid carcinoma with drugs.

 Pathologists at the MedUni Vienna search for new treatment for MTC
In a current study organised in collaboration with the Oxford University (UK), scientists at the Clinical Institute of Pathology at the MedUni Vienna have been able to gather important information that will open up new pathways in the treatment of medullary thyroid carcinoma (MTC). For the first time, it could be possible to prevent these tumours from spreading uncontrollably.

Until now, it was known that malignant neoplasm of the thyroid (tumour stroma) played an important role in the metastasis of these tumours, since only tumours with fibrous areas (desmoplasia) inside the tumour develop metastases. The causes of this form of thyroid change, however, have so far been completely unknown. The pathologists at the MedUni Vienna have now been able to largely solve this puzzle.

MTC: often fatal variant of the most common type of endocrine cancer
Thyroid cancer is the most common type of endocrine cancer. In Austria, around 500 people a year develop this type of tumour, which is generally treatable with success. This is not the case, however, with medullary thyroid carcinoma. This is a slow-growing but frequently metastatic, malignant change in the thyroid gland. The treatment used so far involves as complete a removal as possible of the thyroid and the lymph nodes in the neck. Because of the tumour's slow growth, the radiotherapy and chemotherapy treatment used effectively for other forms of thyroid cancer is of very little benefit. The biggest problem with this is that metastases cannot be destroyed, which is why medullary thyroid carcinoma is often fatal. Peter Birner from the Clinical Institute of Pathology at the MedUni Vienna says: “Previously, there have been no treatment options for MTC metastases, and essentially the patient can only watch and wait as the condition progresses.”

Hypoxia: previously unknown, surprising cause for the development of MTC metastases
The current study demonstrated that a shortage of oxygen supply to the tumour (hypoxia) was closely related to a specific change in the connective tissue that surrounds the tumour (stroma). Oskar Koperek, in charge of the “Endocrine Pathology” working group at the Clinical Institute of Pathology at the MedUni Vienna, says: “The fact that these relatively slow-growing tumours exhibit hypoxia was a big surprise for us. Actually, we assumed that it was only fast-growing tumours that experienced a shortage of oxygen. With MTC, exactly the opposite is true.” In the quest to find the mechanism behind this hypoxic form, the researchers struck gold: in one part of the tumour there were mutations of the Von Hippel Lindau gene which was not previously known in medullary thyroid carcinomas and which apparently triggered the hypoxia.

Analysis of tissue samples reveals further new findings
As part of the study, the scientists at the Medical University of Vienna analysed tissue samples from 100 people who suffered from MTC but who had no family history of the condition. As well as the discovery of hypoxia, the researchers also came across another new finding. Says Birner: “We were able to show that the hypoxia leads to the formation of fibrous areas within tumours. Until now, it had been assumed that this occurred the other way around. Fibrous areas are therefore a symptom rather than the cause of the hypoxia.”

Development of new MTC treatment requires clinical studies
The results of the MedUni Vienna study completely change the perspective on medullary thyroid carcinoma. Consequently, explains Birner: “Hypoxia, which we previously never knew even existed in these tumours, clearly plays an important role in metastasis through the tumour stroma reaction. Since hypoxia pathways (mechanisms that are activated by a shortage of oxygen and make the cancer more aggressive) can be blocked with drugs, this could represent a new treatment option for patients with medullary thyroid carcinoma.” To develop such a new therapeutic approach, however, there would need to be in-depth clinical studies, Birner points out.

The study by the pathologists at the Medical University of Vienna was recently published in the leading "Journal of Pathology”. The study was set up with the support of the mayoral funds of the City of Vienna.

Background: hypoxia in tumours
When tumour cells are not supplied with enough oxygen, clinicians call this hypoxia. Hypoxia prevents the adequate supply of nutrients. Normally, this situation causes the cell to die. Some tumour cells, however, are able to survive despite being hypoxic. As time passes, these cells proliferate. Hypoxic tumour cells are particularly aggressive. They have lost the property of cell death and continue growing in other parts of the body - which is a key trigger for the formation of metastases. It has been known for more than 50 years that hypoxic cells have a strong resistance to radiotherapy. They are also very difficult to treat even with chemotherapy.

Dr. Oskar Koperek (first author) is a specialist in pathology and is in charge of the "Endocrine Pathology" working group at the Clinical Institute of Pathology at the Medical University of Vienna. Extraordinary University Professor Peter Birner (co-author) is a specialist in pathology at the Clinical Institute of Pathology at the Medical University of Vienna.

Koperek O, Bergner O, Pichlhöfer B, Oberndorfer F, Hainfellner JA, Kaserer K, Horvat R, Harris AL, Niederle B, Birner P: “Expression of hypoxia associated proteins in sporadic medullary thyroid cancer is associated with desmoplastic stroma reaction and lymph node metastasis and may indicate somatic mutations in the VHL gene” J Pathol. 2011 Apr 21. doi: 10.1002/path.2926 (Impactfactor : 7,274)