IMMUNOHISTOCHEMISTRY
The tumour cells are positive for estrogen and progesterone receptors (more than 90% of the cells show strong intensity (3+) nuclear staining to estrogen receptor and 35% of the cells show strong unclear intensity (3+) nuclear staining to progesterone receptor). The tumour cells express c-erb-B2 oncoprotein (2+). The external controls for oestrogen and progesterone receptors are positive.
RECEPTOR STATUS
ER and PR positive
c-erb-B2: equivocal (2+) (DAKO Herceptest)
A section of an anonymous pathological report
A report like this, whether from a hospital or a diagnostic service provider, is included in every cancer patient's portfolio. We are talking about a number close to 15 millions worldwide. This one is a breast cancer patient (for breast cancer, there are 280,000 new cases each year in US alone). For description purpose, we may name her Alice.
As stated in this report, three protein biomarkers, Estrogen receptor (ER), Progesterone receptor (PR) and c-erb-B2, were analyzed with a method called Immunohistochemistry (IHC), with the conclusion that ER and PR were positive while c-erb-B2 was undetermined (equivocal).
This is a typical report with IHC. It is only descriptive and hard to follow --- "more than 90% of the cells with strong intensity (3+)", or "35% of the cells with strong intensity (3+)". Especially for c-erb-B2, the only information it provides is "2+". Obviously, an explanation has to be provided in this case ("equivocal").
What is even worse, there is a chance (somewhere around 20 to 30% in c-erb-B2's case), you might get a different result from another pathologist. as this method is known to be affected by the personal bias (something like "beauty is in the eye of beholder", as a "3+" in one pathologist's eyes could be "2+" in another, and 35% for PR can be anything from 20% to 50% depending on the pathologist)
Even if everything is done right, results like this are hard to be used for comparison purpose. In other word, it is very hard for Alice to compare her case with other breast cancer patients. For example, Alice was told to have a very strong ER expression. But really, is she the strongest 5%, or 15%, or even 50%? Information like this would be very helpful for both physicians and patients when combined with other historical data like recurrence or death. Through mathematical analysis at population level, physicians may extract a lot of information for future reference (population studies). Obviously, to rely on IHC to achieve this goal would be extremely challenging.
Nonetheless, IHC remains the only available method to assess the expression levels of tissue markers in Formalin Fixed Paraffin Embedded (FFPE) samples at protein level, and FFPE is the most commonly used method to preserve clinical samples all over the world.
At Quanticision Diagnostics Inc (www.quanticisiondiagnostics.com), our scientists are able to provide solution to remedy the overall situations by developing a brand new form of immunoassay, Quantitative Dot Blot (QDB). It is simple, objective, consistency, easy to be adopted in routine clinical practice. It is also suitable for all forms of tissues (fresh, frozen, or FFPE). In fact, it is the only immunoassay to measure tissue biomarkers as absolute and continuous variables in FFPE samples, thus distinguishing itself from both IHC and ELISA.
Using QDB as the platform, scientists at Quanticision have developed immunoassays to measure over 20 tissue biomarkers for breast cancer patients alone. Instead of providing the results in vague terms, we provide absolute quantitative levels of these biomarkers to patients. For example, Alice may get her receptor status:
ER at 2.50 nmole/g, PR at 1.2 nmole/g, c-erb-B2 at 0.25 nmole/g, with her ER and PR levels identified at top 15% and top 40% respectively.
We are able to evaluate unprecedentedly the potential links among these biomarkers at population levels through mathematical analysis. In fact, based on over 1500 samples analyzed so far, even before c-erb-B2 levels was analyzed, scientists at Quanticision already knew that the chance for Alice to be c-erb-B2 positive was extremely low, as It is rare for one person with ER+ / PR+ would be also c-erb-B2 positive (less than 0.3%). We have also developed the first 3D subtyping method based on the quantitative protein biomarker levels in the world.
We are in the process of developing a growing biomarker database with matching historical data. We believe in the future, we will accumulate sufficient number of patient profiles to identify a group of patients with highly similar biomarker expression profiles as Alice, and recommend Alice the best treatment plan based on the multifactorial analysis of this very group of patients.
Currently we are focusing on breast cancer research, needless to say, this QDB based system can be extended to all types of cancers including Lung, stomach, prostate and colorectal cancers, so "big data" supported diagnosis will become a norm for cancer patients worldwide. We would like to call this brand new field "Quantitative Diagnostics".