Some people hear the terms “tumour markers” and “hormone levels” when they are diagnosed with Neuroendocrine Neoplasms (NENs). That might be confusing or even alarming at the time. Most people diagnosed with cancer will have had a form of medical testing at some point in their life, i.e. the sampling and testing of blood, urine, saliva, stool or body tissue. With NENs, the medical staff are just measuring the content of a ‘substance’ and then taking a view whether this is normal or not based on pre-determined ranges. These tests are normally done as a physician’s reaction to symptom presentation or maintenance/surveillance of an existing diagnosed condition. Sometimes, abnormal results will lead to more specialist tests.
In cancer, these tests are frequently called ‘markers’. Most tumour markers are made by normal cells as well as by cancer cells; however, they are produced at much higher levels in many cancerous conditions.
These substances can be found in the blood, urine, stool, tumour tissue, or other tissues or bodily fluids of some patients with cancer. Most tumour markers are proteins. However, more recently, patterns of gene expression and changes to DNA have also begun to be used as tumour markers, e.g. see NETest below. Many different tumour markers have been characterised and are in clinical use. Some are associated with only one type of cancer, whereas others are associated with two or more cancer types. No “universal” tumour marker that can detect any type of cancer has been found.
There are some limitations to the use of tumour markers. Sometimes, noncancerous conditions can cause the levels of certain tumour markers to increase. In addition, not everyone with a particular type of cancer will have a higher level of a tumour marker associated with that cancer. Moreover, tumour markers have not been identified for every type of cancer. Tumour markers are not foolproof and other tests and checks are usually needed to learn more about a possible cancer or recurrence.
I’d also like to talk about a group of associated tests, in particular, hormone levels as these tests are really important to help determine the type of Neuroendocrine Tumour. NETs will sometimes over-secrete hormones, and this can give clues to the type. The constraints mentioned above apply to hormone levels and other tests to a certain extent. NETs are a heterogenous collection of tumours, thus why testing can also be really complex with some tests for some types and other tests for other types.
The sequencing of marker testing may have been different for many patients. In my own experience, I had a biopsy and then the specialist tests for NETs were carried out. So regardless of the results of my marker tests, I was to be diagnosed with NETs. Those with lengthy and difficult diagnostic phases will perhaps have had a different sequence with the biochemical markers providing evidence for further tests to formally diagnose. Markers alone will normally not be enough for a diagnosis, but they do, however, feed into the treatment plan and provide a baseline at diagnosis and for tracking going forward.
Routine Testing – the post will not cover routine blood tests (i.e. complete blood count etc). Although they may point to a problem, these tests do not necessarily diagnose a particular type of NET without other supporting evidence (they can give clues though, e.g. my very low hemoglobin score led to more checks including a CT scan ….. and bingo).
Biopsy Testing – Technically, the Immunohistochemical ‘stains’ used in biopsy testing are tumour markers, but I’ll not be discussing that today. I did cover some of the output of biopsies in my blog on Biopsies – tissue is the issue
Genetic Testing. This is very specialised and not everyone needs to have it done, but you may find my Genetics and NETs article is of interest.
Molecular Features of NENs. Molecular features are now becoming critical for precise diagnosis, risk stratification, and identifying therapeutic targets. This is mainly for pancreatic NETs currently and is an emerging theme since WHO Classification of NENs was published in 2022. To follow.
Next Generation Sequencing (NGS). See below as an additional subject matter for information only.
The use of markers tends to be different on an international basis, e.g. specific marker tests can be developed in-country by independent labs. Testing can also vary in the same country as in-country labs use different commercially available ‘testing kits’. Not all tests are available in all countries.
Reference ranges must be quoted in patient group questions/answers
Reference ranges can be dependent on many factors, including patient age, gender, sample population, and test method, and numeric test results can have different meanings in different laboratories. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the tests to obtain the reference range if you do not have the lab report. Moreover, the ‘normal’ test range can vary from hospital to hospital, even within the same tests. I suspect clinical staff have their own versions of risk thresholds when dealing with test results. Even when results are just above or below, individual physicians can take their own view in a subjective manner. Testing is best done at the same lab each time if possible.
There’s a great website called LabTestsOnline which can describe each test. It’s peer-reviewed, non-commercial and patient-focused but just please note you should always refer to your own lab ‘normal ranges’ which will be printed on your test results. For these reasons, you will not find reference ranges for the majority of tests described on this web site. The link above will take you to the list of ‘country’ affiliated versions with specific information on a country basis.
Here’s some tips I always give people:
1 – Always try to get your own copy of results. Unless you have an online app for this purpose, get them on paper as this should give your reference ranges which are important for asking question in patient online groups. Track them yourself (I use a spreadsheet).
2 – When comparing results inside patient forums, always add the range and if possible, the unit of measurement (i.e. g/L, mmol/L, umol/L etc etc). Failure to do this can at best confuse, and at worst frighten patients. Compare apples with apples not with pears! (this is why it’s important to know the unit of measure and the reference range in addition to the figure).
3 – Don’t get too excited about rises if the test is still inside the normal range – normal is normal!
4 – Don’t get too excited about rises taking you just outside of normal range – your doctors are looking for bigger spikes.
5. Don’t get too excited about a single test result, your doctors are looking for trends, although suspicious, a single test result is not much to go on and there may be other reasons for the elevation.
Certain tests can be anatomy related so to add context and to prevent big repetitive lists when using the terms ‘foregut’, ‘midgut’ and ‘hindgut’, you may find this graphic useful.
Although some routine blood markers (complete blood count etc) are useful in NETs, it’s pretty much impossible to cover these in any general detail. I’m going to focus on tumour and hormone associated markers. Specialists often use the term ‘biomarkers’ for tumour markers.
There are many markers involved with NETs. Some do different jobs, and some are just variants measuring the same thing (more or less efficiently). You may also see something called ‘gold standard’ in reference to NET Tumour markers. Although thinking is changing (more on this below) and can vary from country to country, it is generally accepted that Chromogranin A is the gold standard markers for tumour bulk. I’m also aware that US doctors are reducing the dependency on CgA and using Pancreastatin instead (although many are measuring both indicating that Pancreastatin is also not reliable).
NETs are known to be heterogeneous in nature (i.e. consisting of or composed of dissimilar elements; not having a uniform quality throughout). Whilst some markers can be used widely, it follows that there are many very specialist marker tests for individual types of NET. I think this applies to 3 broad categories of NETs: Tumours known to potentially oversecrete Serotonin and perhaps others (mainly midgut), Pancreatic NETs (or pNETs) secreting various hormones by type; and other less common types and/or syndromes which might be considered by some to be even more complex than the former two and in some cases, there are big overlaps. p.s. it’s not all about Serotonin!
Another interesting thing about NET markers is that an undiagnosed patient may undergo several specialist tests to eliminate the many possibilities that are being presented as vague and common symptoms. Sometimes this is necessary to eliminate or ‘home in’ on a tumour type or syndrome/hormone involved (it’s that jigsaw thing again!).
Markers too can be divided into broad categories, those measuring how much tumour is in your body and its growth potential and those measuring how functional (or not) those tumours are. The latter can probably be expanded to measure/assess excess hormone secretion and syndromes.
Chromogranin is an acidic protein released from chromaffin cells and nerve terminals. This statement alone might explain why it is a good marker to use with NETs for measuring tumour bulk. Depending on the test kit being used, you may see test results for Chromogranin A (CgA) and Chromogranin B (CgB) – the inclusion of CgB tends to be confined to Europe.
There’s controversy surrounding this test, particularly in USA where even using the test is shunned by specialists. However, a recent US study (Oct 2024) confirms changes in serial measurements of serum CgA had a favourable specificity and NPV, making this test a useful adjunct to routine radiographic monitoring. Go figure.
My comprehensive post on Chromogranin A can be found by clicking here or on the picture below (this includes new of the study mentioned above).
In effect, this marker does the same job as CgA. Interestingly, Pancreastatin is actually a fragment of the CgA molecule. There have been many studies (mainly in the US) indicating this is a more efficient marker than CgA, and not only because it is said not as influenced by the use of PPI. It has also been suggested that it’s more sensitive than CgA and therefore capable of detecting early increases in tumour burden. It has also been suggested it can be an indication of tumour ‘activity’ (whatever that means). It is widely used in the US and some physicians will use it in preference to CgA (…..although from what I read, CgA also seems to be tested alongside). 2024 – this hasn’t taken off and is not recommended to be used for informing treatment.
This is not a well-publicised test. However, it is something used in USA, but I’d like to hear from others to validate its use elsewhere. In a nutshell, this test, which only applies to well-differentiated midgut NETs, appears to have some prognostic indication. I discovered this test in the (now out of date) ISI NET Guidance, and it’s backed up by a study authored by names such as Woltering, O’Dorisio, Vinik, et al. This is not a one-off test but one designed to be taken serially, i.e. a number of consecutive tests. These authors believe that NKA can also aid in the early identification of patients with more aggressive tumors, allowing for better clinical management of these patients. NKA is sometimes called Substance K. Edit 2024, I do not see this used regularly, anywhere.
In patients with suspected NET who have no clear elevations in the primary tumour markers used to diagnose these conditions, an elevated serum NSE level supports the clinical suspicion. Neuron-Specific Enolase (NSE) is a neuron-specific isomer of the enolase enzyme, found in neurons and neuroendocrine cells. Assessment of NSE alone is rarely adequate for diagnostic purposes of NETs, given that only 30 to 50% of which are mostly poorly differentiated tumours (Neuroendocrine Carcinoma. Serum NSE concentrations are often increased in patients with other diseases, such as thyroid cancer, prostate carcinoma, neuroblastoma, and small cell lung carcinoma (SCLC), the latter is the most common type of Neuroendocrine Neoplasm.
This has been around for some time but hasn’t really taken off. It is more of a molecular test which is way tumour markers for cancer is heading. Read more here or see special section below. Click here.
So far, I’ve covered basic tumour markers which have a tumour bulk and/or prognostic indication. This section is a slightly more complex area and many more tests are involved. There’s often a correlation between CgA/Pancreastatin and these type of markers in many patients i.e. a serial high level of CgA might indicate a high level of tumour bulk and therefore increased production of a hormone in patients with a syndrome or oversecreting tumour. However, it frequently does not work out like that, particularly when dealing with non-functioning tumours.
The type of marker for this element of NET diagnosis and surveillance will vary depending on the type of NET and its location (to a certain extent). Like tumour bulk/growth, there might be different options or test variants on an international basis. There are too many to list here, so I’ll only cover the most common.
There are a few markers in use for measuring the functionality of this grouping of tumours. This tumour group has a tendency to secrete excess amounts of the hormone Serotonin. Please also note there may be other hormones of note involved. The antiquated and misleading term ‘Carcinoid’ is sometimes used as a descriptor for these tumours and more and more NET scientific organisations and specialists are now avoiding use of this term.
Many people with NET think they must also have so called carcinoid syndrome and they must be tested for serotonin. This is simply not accurate and has been caused by bad moderation in patient groups, inaccurate/incomplete patient advocate websites, and ill-informed doctors who only want to check this particular hormone (I understand why it might be checked alongside the other hormonal syndrome tests outside midgut, but not alone). A spotlight on carcinoid syndrome can be found by clicking here.
Serotonin secreting tumours are mainly found in midgut tumours. Rarely in hindgut and foregut.
There are a few markers in use for measuring the functionality of this grouping of tumours. This tumour group has a tendency to secrete excess amounts of the hormone Serotonin although it differs depending on the area of the primary. For example, hindgut tumours tend to secret lower levels than foregut and midgut and therefore this test may present within range. Please also note there may be other hormones of note involved. The antiquated and misleading term ‘Carcinoid’ is sometimes used as a descriptor for these tumours and more and more NET scientific organisations and specialists are now avoiding use of this term. Measuring raw serotonin may show skewed results as it fluctuates throughout the day and is therefore not the gold standard. That accolade belongs to 5-HIAA.
This is a metabolite of Serotonin thus why it’s a useful thing to measure to assess functionality in this grouping of tumours. 5HIAA is actually the ‘gold standard’ test for functioning serotonin secreting tumours and is available in both urine and serum versions (the latter is not as widely available as the urine version). There is a totally separate article on 5-HIAA which you can read by clicking here or on the picture below.
We don’t measure brain serotonin because it is not directly related to carcinoid syndrome, nor is diagnostic of carcinoid syndrome. But I wanted to incude it here to cler up some common confusion! Those who have read my Serotonin blog will be aware that the human body has two separate stores of serotonin. Around 95% is said to be for the body (or gut) and 5% for the brain (or peripheral). These two stores do not share with each other due to the blood brain barrier. Serotonin is manufactured in each store and remains there, it cannot cross the blood brain barrier. It follows that testing for Serotonin covers only the body levels as it is taken from urine or a blood draw normally from an arm. Click here to read more.
Testing will be different depending on the Type:
The key makers are CgA and Gastrin although Gastrin may not be elevated in Type 3 or in Gastric NEC. Gastrin ph is useful to differentiate between Type 1 and Type 2. 5-HIAA can be considered but true Carcinoid Syndrome is almost unheard of in Gastric NETs.
Read more about Gastric NETs here:
Pan NETs can be very difficult to diagnose and not only because they share some presentation similarities to their exocrine counterparts. Some Pan NETs actually comprise tumours arising in the upper part of the duodenum (small intestine) close to the Pancreas. Moreover, more than half of Pan NETs are non-functional which increases the difficulty in suspecting and then finding the tumours. However, where there is clinical presentation or suspicion, these symptoms can lead to the appropriate testing to support the output of scans. The fasting gut profile mentioned above can be useful in identifying the offending hormones when the type of NET is not yet known.
A gut hormone screen is used for the diagnosis of a variety of endocrine tumours of the pancreas area. Analysis includes insulin, gastrin, VIP, somatostatin, and glucagon, but there may be others depending on processes used by your ordering specialist or hospital. You may see this referred to as a ‘Fasting Gut Profile’ or a ‘Fasting Gut Hormone Profile’. Some hospitals will include 5-HIAA but carcinoid syndrome is very uncommon with around 2% mentioned in many cases. Pancreatic polypeptide (PP) PPomas, while they may secrete pancreatic polypeptide, do not cause a well-defined clinical syndrome. This is why ENETS and other major guidelines (e.g., WHO, NANETS) typically classify them as non-functional NETs, even if they are biochemically active.
There are several types of functional pNETs (although some can present in the duodenum), each with its own syndrome or hormone issue and the Gut Hormone Profile mentioned above is one way to check whether a pNET is functional or non-functional, or at least provide further clues. When they are suspected due to the presenting symptoms, the markers that could be used are listed below. These types of tumours are complex and can be related to one or more syndromes. A patient may be tested using multiple markers to include or exclude these. Depending on other factors, some physicians may recommend additional marker testing
The table below is taken from ENETS 2023 functional guidelines– read more here
| Clinical features | Biochemical diagnosis | Test | |
|---|---|---|---|
| Insulinoma | Fasting hypoglycaemia | (Pro-)insulin, C-peptide during hypoglycaemia | Endogenous hyperinsulinaemic hypoglycaemia |
| Gastrinoma | Reflux, dyspepsia, ulcers, PPI-responsive diarrhoea | Fasting gastrin >10x URL & gastric pH ≤2 | Zollinger-Ellison syndrome |
| Glucagonoma | Diabetes mellitus, necrolytic migratory erythema, deep venous thrombosis, depression, cheilitis/stomatitis, normocytic anaemia, weight loss, hypoaminoacidaemia, cardiomyopathy | Fasting glucagon >500 pg/mL | |
| VIPoma | Secretory diarrhoea, hypokalaemia, achlorhydria hypercalcaemia | Fasting VIP >60 nmol/L | Verner-Morrison syndrome |
| ACTHoma | Hypokalaemia, diabetes mellitus, muscle weakness, hypertension, moon facies, oedema | 24 h urine cortisol, midnight salivary cortisol, cortisol after 1 mg dexamethasone overnight, ACTH | Ectopic Cushing’s syndrome |
| PTHrPoma | Hypercalcaemia, hypophosphataemia, elevated alkaline phosphatase | PTH-rP >URL, Suppressed PTH | Humoral hypercalcemia of malignancy |
| Carcinoid syndrome | Diarrhoea, flushing, asthma, fibrosis | Urine 5-HIAA >50 μmol/24 h Elevated plasma 5-HIAA or serotonin | |
| Calcitoninoma | Diarrhoea, flushing | Calcitonin >> URL | |
| GHRHoma | Acral overgrowth, cardiomegaly | IGF-1 >2x URL GHRH >250 mg/L | Ectopic acromegaly |
| Somatostatinoma | Diabetes mellitus, diarrhoea, steatorrhea, cholelithiasis, hypo−/achlorhydria, weight loss, central hypothyroidism | Fasting somatostatin >> URL |
Lung/thymic tumours may be associated with carcinoid syndrome as well as
hypercortisolemia (Cushing syndrome). For carcinoid syndrome see ‘Serotonin’ above.
Cushing’s syndrome. This syndrome normally involves the adrenal and pituitary glands. However, the over secretion can often be ectopic (released outside these areas (the latter is often found in lung or thymic). See more on ACTH/Cushing’s/Cortisol below. The workup normally includes an overnight dexamethasone suppression test. The panel of tests should also work out whether the Cushing’s is ACTH dependant or independent.
Hindgut NET. NETs of the colon or rectum are rarely functional. This area is normally unable to manufacture serotonin from its precursors. However, symptomatic cases, particularly metastatic cases, may benefit from a 5-HIAA test.
Pheochromocytoma/Paraganglioma – catecholamine-producing tumours. Plasma and urine catecholamines, plasma free total metanephrines, urine total metanephrines, vanillylmandelic acid (VMA). Read more here.
Medullary Thyroid Cancer. Medullary thyroid cancer (MTC) starts as a growth of abnormal cancer cells within the thyroid – the parafollicular C cells. In the hereditary form of medullary thyroid cancer (~20% of cases, often called Familial MTC or FMTC), the growth of these cells is due to a mutation in the RET gene which was inherited. This mutated gene may first produce a premalignant condition called C cell hyperplasia. The parafollicular C cells of the thyroid begin to have unregulated growth. In the inherited forms of medullary thyroid cancer, the growing C cells may form a bump or nodule in any portion of the thyroid gland. Unlike papillary and follicular thyroid cancers, which arise from thyroid hormone-producing cells, medullary thyroid cancer originates in the parafollicular cells (also called C cells) of the thyroid.
These cancer cells make a different hormone called calcitonin, which has nothing to do with the control of metabolism in the way thyroid hormones do. The other test often seen in MTC is Carcinoembryonic Antigen (CEA). CEA is a protein that is usually found in the blood at a very low level but might rise in certain cancers, such as medullary thyroid cancer. There is no direct relationship between serum calcitonin levels and extent of medullary thyroid cancer. However, trending serum calcitonin and CEA levels can be a useful tool for doctors to consider in determining the pace of change of a patient’s medullary cancer. There is one more test that can be used to identify patients with MCT who have normal baseline levels of calcitonin – the pentagastrin stimulation test. Pentagastrin normally stimulates the secretion of calcitonin from the C cell. Women may not respond due to the presence of estrogens. The response in persons with MCT is an exaggeration of the normal response to pentagastrin. Be aware there is a familial variant of MCT (often called FMCT) and it’s always useful to identify members of a family with a known familial form of MEN2 and MCT (RET mutation).
(please note there are extremely rare occurrences of elevated calcitonin from places outside the thyroid (e.g. ectopic scenarios) – read more here.)
Parathyroid– Parathyroid hormone (PTH), Serum Calcium. Parathyroid hormone (PTH) is secreted from four parathyroid glands, which are small glands in the neck, located behind the thyroid gland. Parathyroid hormone regulates calcium levels in the blood, largely by increasing the levels when they are too low. A primary problem in the parathyroid glands, producing too much parathyroid hormone causes raised calcium levels in the blood (hypercalcaemia – primary hyperparathyroidism). You may also be offered an additional test called Parathyroid Hormone-Related Peptide (PTHrP). They would probably also measure Serum Calcium in combination with these types of tests. The parathyroid is one of the ‘3 p’ locations often connected to Multiple Endocrine Neoplasia – MEN 1 – see MEN below.
Pituitary/Cushings – Adrenocorticotropic hormone (ACTH), Cortisol. For purely Pituitary reasons, tests for Growth hormone (GH), Prolactin, Insulin growth factor 1 (IGF1) may be conducted.
HPA AXIS – It’s important to note something called the HPA axis when discussing pituitary hormones as there is a natural and important connection and rhythm between the Hypothalamus, Pituitary and the Adrenal glands.
Adrenocorticotropic hormone (ACTH) is made in the corticotroph cells of the anterior pituitary gland. Its production is stimulated by receiving corticotrophin releasing hormone (CRH) from the Hypothalamus. ACTH is secreted in several intermittent pulses during the day into the bloodstream and transported around the body. Like cortisol (see below), levels of ACTH are generally high in the morning when we wake up and fall throughout the day. This is called a diurnal rhythm. Once ACTH reaches the adrenal glands, it binds on to receptors causing the adrenal glands to secrete more cortisol, resulting in higher levels of cortisol in the blood. It also increases production of the chemical compounds that trigger an increase in other hormones such as adrenaline and noradrenaline. If too much is released, the effects of too much ACTH are mainly due to the increase in cortisol levels which result. Higher than normal levels of ACTH may be due to:
Cushing’s disease – this is the most common cause of increased ACTH. It is caused by a tumor in the pituitary gland (PitNET), which produces excess amounts of ACTH. (Please note, Cushing’s disease is just one of the numerous causes of Cushing’s syndrome). It is likely that a Cortisol test will also be ordered if Cushing’s is suspected.
This is a steroid hormone, one of the glucocorticoids, made in the cortex of the adrenal glands and then released into the blood, which transports it all round the body. Almost every cell contains receptors for cortisol and so cortisol can have lots of different actions depending on which sort of cells it is acting upon. These effects include controlling the body’s blood sugar levels and thus regulating metabolism acting as an anti-inflammatory, influencing memory formation, controlling salt and water balance, influencing blood pressure. Blood levels of cortisol vary dramatically, but generally are high in the morning when we wake up, and then fall throughout the day. This is called a diurnal rhythm. In people who work at night, this pattern is reversed, so the timing of cortisol release is clearly linked to daily activity patterns. In addition, in response to stress, extra cortisol is released to help the body to respond appropriately. Too much cortisol over a prolonged period of time can lead to Cushing’s syndrome.
Cortisol over secretion can be associated with Adrenal Cortical Carcinoma (ACC) which can sometimes be grouped within the NET family for practical purposes. Other hormones related to ACC include:
Androgens (e.g. Testosterone) – increased facial and body hair, particularly females. Deepened voice in females.
Estrogen – early signs of puberty in children, enlarged breast tissue in males.
Aldosterone – weight gain, high blood pressure.
Adrenal Insufficiency (Addison’s Disease) occurs when the adrenal glands do not produce enough of the hormone cortisol and in some cases, the hormone aldosterone. For this reason, the disease is sometimes called chronic adrenal insufficiency, or hypercortisolism.
A tumour outside the pituitary gland, producing ACTH (also called ectopic ACTH). With NETs, this is normally a Thymus, Lung, Pan NET or Pheochromocytoma.
Misc Tests
Carcinoid Heart Disease (CHD) (Hedinger syndrome). I’m not really talking directly about a tumour here but thought it would be useful to include a blood test called N-terminal pro-B-type natriuretic peptide (NT-proBNP). This is a protein produced by the heart that helps diagnose and monitor heart failure. For those not offered an annual Echocardiogram and/or or are ‘non-syndromic’ with normal levels of 5-HIAA, NT-proBNP is a screening test that can give an indication of any heart issue which might then need further checks. This mostly affects metastatic midgut NETs but very rarely in other serotonin secreting locations. Read more about carcinoid heart disease by clicking here.
I included it separately here because evidence is lacking. It is, however, usually only associated with foregut tumours. It’s potentially a controversial area as the test is normally done to help confirm a diagnosis of anaphylaxis, mastocytosis, or mast cell activation. But that is for regular issues not necessarily evidence of a tumour secretion of histamine. Histamine is not routinely used in the diagnosis of NETs or any NET hormonal syndromes – go figure.
– read more by clicking here or on the picture below.
A liquid biopsy is a simple and non-invasive alternative to surgical biopsies which enables doctors to discover a range of information about a tumour through a simple blood sample. Liquid biopsy is very generic name but what I really mean are Mono or Multi-Analyte Circulating Biomarkers
Traces of the cancer’s DNA in the blood can give clues about which treatments are most likely to work for that patient. The techniques are maturing but not ready for routine deployment in Neuroendocrine Neoplasms (NEN). The reference below indicates that to date, there is no robust enough evidence for the use of CTCs as diagnostic tools in NENs.
The types of test which are potential novel Multi-Analytes Biomarkers for NEN include:
Circulating tumor DNA (ctDNA),
MicroRNAs (miRNAs),
Wren’s NETest (see below).
Read more on this highly technical subject by clicking here
The Neuroendocrine testing capability from Wren Laboratories is not new. They’ve been around for some time and I remember the “Wren Test” being talked about some years ago. Back then it was receiving mixed reviews from patients and physicians. Looking at where they are in 2020, it looks like they’ve been busy and have new data.
According to their website, the NETest is a non-invasive procedure that uses a blood sample to inform your doctor what the activity of your tumor is at the time your blood was drawn. Use of the NETest provides additional information about disease status that is complementary to imaging and may decrease radiation exposure by decreasing the need for repetitive imaging. NETest provides an assessment of treatment responses in neuroendocrine tumor patients in conjunction with standard clinical assessment. Interpretation of the test will facilitate identification of active disease and enable a determination of the efficacy of the current treatment modality. NETest is as easy as having your blood drawn and provides clinicians and patients with the information to better manage treatment.
Read more by clicking here
The is not something that would diagnose a Neuroendocrine Neoplasms but may offer cluses. NGS is a high-throughput method for sequencing DNA or RNA, allowing simultaneous analysis of millions of fragments. It’s used for:
• Whole genome and exome sequencing
• Targeted gene panels
• RNA sequencing
• Detection of mutations, fusions, copy number variations, and more
NGS in the United States
• Clinical Use: Widely adopted in oncology, rare disease diagnostics, pharmacogenomics, and infectious disease tracking.
• Platforms: Illumina, Thermo Fisher (Ion Torrent), PacBio, Oxford Nanopore.
• Growth: The U.S. NGS market is projected to reach $16.57 billion by 2033, driven by personalized medicine, automation, and agricultural/environmental applications.
• Access: Available through hospitals, academic centers, and commercial labs (e.g., Foundation Medicine, Invitae).
• Regulation: FDA oversees clinical-grade tests; CLIA certification is required for labs.
• Insurance: Coverage varies by provider and indication; prior authorization often needed.
NGS in the United Kingdom
• Clinical Use: Integrated into NHS Genomic Medicine Service for rare diseases, cancer, and prenatal diagnostics.
• Platforms: Similar to the U.S., with emphasis on short-read sequencing (Illumina) and growing interest in long-read technologies.
• Access: Delivered through NHS Genomic Laboratory Hubs and commercial providers like Source BioScience.
• Regulation: Governed by UKAS and ISO standards; NHS labs follow rigorous validation protocols.
• Cost: Free to patients if clinically indicated and referred by a specialist.
Emerging Role — But Not Primary Diagnostic Tool
• NGS is not currently a frontline diagnostic tool for most neuroendocrine tumors (NETs). Diagnosis still relies on histopathology, immunohistochemistry (IHC), and clinical features.
• However, NGS is increasingly used for genomic profiling, especially in:
• Poorly differentiated neuroendocrine carcinomas (NECs), which show higher tumor mutational burden (TMB) and more actionable mutations.
• Identifying hereditary predispositions in select NET cases (e.g., MEN1, SDHx mutations).
• Therapeutic decision-making, particularly when standard options are exhausted or targeted therapies are considered.
Tumour Markers and Hormone levels – complex subject! This article is designed for patients to understand in a simple way and only covers the basics.
Update 2024: This useful summary published in 2024 is a great summary of where we are and where we might go with “Biomarkers” for Neuroendocrine Neoplasms. Interestingly they include the use of PET scans including FDG and somatostatin receptor based imaging as treatment informing. I guess it also helps with diagnosing difficult and complex cases. Click here to read more.
If you are a medical professional, although some of the detail may have been refined since 2019, I recommend this article as a primer to the subject:
Herrera-Martínez, A., Hofland, L., Gálvez Moreno, M., Castaño, J., de Herder, W., & Feelders, R. (2019). Neuroendocrine neoplasms: current and potential diagnostic, predictive and prognostic markers, Endocrine-Related Cancer. Retrieved Apr 5, 2019, Click here
Thanks for reading.
Blog Facebook. Like this page please.
Personal Facebook. Like this page please.
Awareness Facebook Like this page please.
Follow me on X (formerly twitter)
Check out my online presentations
Check out my WEGO Health Awards
A Global first for NET. Omni 128cm Total Body PET at the Peter MacCallum Cancer Centre in Melbourne Australia. According to Professor Michael Hofman, they
My diagnosis came with many strange words including, “carcinoid” and “neuroendocrine” ……… can you spell that please, I said to the doctor. I had a
Ronny Allan’s ‘PoNETry’ © series can be shared with poetry credit to: RonnyAllan.NET Thanks for reading Ronny I also have one about Lanreotide (or “butt
When I was diagnosed, I didn’t even feel ill. It was therefore a bit of a shock being told I had metastatic cancer, advanced enough to
I was assessing performance of the awareness period in November 2025 on Facebook and was astonished to find the size of my reach on that
Here is the monthly summary of November 2025 on RonnyAllan.NET – Every share helps someone understand or even work towards a diagnosis, discovery of the
Discover more from Ronny Allan – Living with Neuroendocrine Cancer Subscribe to get the latest posts sent to your email. Type your email… Subscribe
Bone metastases in Neuroendocrine Tumours (NET) Many of you will know that I am a stage IV small intestine NET and I have one bone
What is Radioligand Therapy? When you browse the internet, you may see the term “Radioligand Therapy (RLT)” and wondered what it was. There’s a simple
I would also mention those who contributed to my “Tea Fund” which resides on PayPal. You don’t need a PayPal account as you can select a card but don’t forget to select the number of units first (i.e. 1 = £4, 2 = £8, 3 = £12, and so on), plus further on, tick a button to NOT create a PayPal account if you don’t need one. Clearly, if you have a PayPal account, the process is much simpler
Through your generosity, I am able to keep my sites running and provide various services for you. I have some ideas for 2023 but they are not detailed enough to make announcements yet.
This screenshot is from every single post on my website and depending on which machine you are using, it will either be top right of the post or at the bottom (my posts are often long, so scroll down!)
Subscribe to get the latest posts sent to your email.
