Clapper, Patti, Schweizer and Mason

A recent study in Switzerland explored particular prognostic and diagnostic markers in attempts to improve selection of patients diagnosed with malignant pleural mesothelioma (MPM) who would most benefit from treatment.  Mesothelioma is primarily linked with exposure to asbestos, which most often occurs occupationally.

Mesothelioma is a rare form of cancer that begins in the mesothelium, or protective sac lining the heart, abdomen and lungs.  Pleural mesothelioma is the one that affects the lungs and is the most common type.  The pleura consists of two thin membranes that line the entire surface of the lung, including the areas between the right and left lobes. 

Mesothelioma tumors generally begin in one lobe,  then spread to the other as well as to other parts of the body.  MPM tumors are highly invasive, chemoresistant, and aggressive.  The exposure to asbestos that caused the mesothelioma occurred decades before actual onset of symptoms.

The Swiss study explored the connection between the aggressiveness of a mesothelioma tumor in the context of the interaction between epithelial-to-mesnchymal transition (EMT)and  mesnchymal-epithelial transition (MET).  MET is the opposite process of EMT and affects the progression, invasion and metastasis of mesothelioma tumors.

There are three histologic types of mesothelioma:

·         Epitheliod- the most common type, accounting for up to 70% of all cases, which also carries the best prognosis

·         Sarcomatoid- a more aggressive form of mesothelioma that accounts for 10-15% of all cases.

·         Biphasic- also referred to as ‘mixed’, accounting for 10-15% of cases.

The study confirmed that mesotheliomas of sarcomatoid histotype have the poorest prognosis.  Longer overall survival times were associated with high expression of phosphatase and tensin homologue (PTEN) and low expression of cytosolic periostin.  PTEN is a protein that acts as a tumor suppressor gene.  Mutations of this gene is linked with the development of mesothelioma and other cancers.  PTEN prevents cancer cells from growing and dividing too rapidly by regulating cell cycles.  When PTEN is properly functioning, it signals cells to stop dividing and causes apoptosis, or programmed cell death which prevents the kind of cell growth that can lead to tumors forming. 

The study also found that the EMT protein periostin is associatied with more advanced tumor stage and grades in mesothelioma.  Overexpression of periostin was closely linked with increasing TNM stage.  The TNM stage is often used to determine how advanced the mesothelioma tumors are and is based upon the extent of the tumor (T), if it’s spread to lymph nodes (N) and whether the tumors have metastasized (M).

The researchers suggest further investigations into prognostic markers that could help identify mesothelioma patients who are at the highest risk for lowest survival times.  Continued studies may also help to study cellular responses that could improve survival times, decrease proliferation of cancer cells, and slow spreading and migration of tumors.   They suggest more clinical trials in patients who have undergone multimodal treatments, such as chemotherapy, surgery and radiation therapy.

If you have been diagnosed with mesothelioma and would like to find out more about clinical trials being offered in your area and for your particular type of mesothelioma, visit the National Cancer Institute website or speak to your healthcare team.