Enhancing diagnosis of PHTS

Introduction

Because signs of PHTS are often different from person to person, PHTS is often hard to recognise which may lead to delayed diagnosis. Some features of PHTS, such as a larger head size, developmental delay, or skin changes, can also happen in people without PHTS, which makes diagnosis even more difficult.

Getting the right diagnosis matters because people with PHTS have a higher risk of certain cancers and therefore benefit from regular checks (called cancer surveillance or screening) to find problems early. A diagnosis can also help other family members learn whether they are at risk and may want genetic testing or counselling.

PTEN Research is funding projects that could help people with PHTS get a diagnosis earlier and using approaches that could help support doctors who may not be experts at recognising PHTS. Earlier and more reliable diagnosis can mean earlier monitoring, better support, earlier cancer detection and more informed choices for the whole family.

Project 1 goals

This study which is conducted by researchers at The Ohio State University (US), Cleveland Clinic Foundation (US) and Radboud University Medical Center (the Netherlands) is investigating whether a test called PTEN immunohistochemistry staining could help identify people with PHTS.

This test is already used in many hospital laboratories for other purposes, and looks at tissue samples under a microscope to see what amount of PTEN protein is present. A similar approach has been successfully used to identify people with other genetic conditions causing high cancer risk, such as Lynch syndrome.

Project 1 overview

The researchers will investigate if there is a difference in the level of PTEN protein in tissue from people with PHTS compared to people with other inherited cancer conditions and people without a known inherited cancer risk.

This study will include almost 1,000 non-cancerous tissue samples from small growths in the lower part of the digestive tract (colorectal polyps) as well as thyroid and breast tissue collected from people with PHTS and people without PHTS (controls).

Project 2 goals

This study aims to develop a computer-based method to help find adults who may have PHTS but have not yet been diagnosed. 

The computer algorithm uses patterns in electronic medical record data, such as tests and symptoms an individual has had, to flag people whose features are similar to PHTS. 

The scientists leading this work have already developed a similar approach to identify children who should be referred for PTEN genetic testing, and they are now expanding the approach to adults.

Project 2 overview

The researchers will first create a list of PHTS symptoms that they will look for in the medical record data. They will use published literature but also talk to expert clinicians and patient organisations to better understand symptoms of PHTS and should be included in the algorithm. 

They will then use very large research datasets containing medical record data from over 240 million people from the US and UK to develop the algorithm. As some of the datasets also contain genetic data, these can be used to see how well the algorithm works.

Project 2 anticipated outcomes

If the method works, it could be built into electronic medical record systems to automatically identify people who have symptoms consistent with PHTS. For such individuals, following discussion with their doctor, it may be appropriate to consider PTEN genetic testing. 

The researchers also plan to make their method freely available so that it can be used by anyone or further developed to also work for other health conditions.