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  • decodeMR Team

Molecular Diagnostics -Technical approach to analyze biological markers - Q&A session with an Expert


(Focus- New Zealand)


To share the pertinent facts and findings with our readers regarding an enormously used biological technique called Molecular Diagnostics, decodeMR presents an interview of Dr. Valdimir Osipov, an Anatomical Pathologist from New Zealand wherein he has shared his views on the evolution of molecular cancer diagnostics.


Dr. Vladimir Osipov is an Anatomical Pathologist, currently serving in Whangarei Hospital, New Zealand.




Lung cancer treatment has changed in the past five years, and so has the testing. EGFR testing is routine nowadays; all lung adenocarcinoma samples go straight for EGFR detection by PCR.

How do you describe the evolution of cancer molecular diagnostic tests in the last five years in New Zealand? How does it compare with the rest of the world?

Dr. Vladimir: Within the last five years, the Ministry of Health has made mismatch repair (MMR) immunohistochemistry mandatory for colorectal cancers. This test is necessary in order to exclude Lynch syndrome, and provides prognostic and further treatment-related information, depending on the cancer stage. BRAF mutational analysis, which can also be done by immunohistochemistry, provides further prognostic information. BRAF testing in colorectal cancer cases can also be done with polymerase chain reaction (PCR), however, immunohistochemistry is much cheaper and as accurate. Now we use immunohistochemistry for all colorectal cancer patients. If the BRAF turns out to be negative in patients with MLH-1 / PMS-2 deficient cancers, then the sample is sent to a reference lab for MLH1 promoter methylation. There are two labs in Auckland (one government and one private) that can do methylation studies. For endometrial cancers, you would need to do MLH 1 promoter methylation right away if it is MMR deficient tumor. These standards are relatively new and are similar to the ones used in other countries with advanced healthcare.

Another test that came up in the past five years is PD-L1. Testing is done by immunohistochemistry and requires pathologists to have additional training in the interpretation of that test. Keytruda, a drug targeting PD-L1 expressing tumors, is now widely used in the treatment of various cancers.

Lung cancer treatment has changed in the past five years, and so has the testing. EGFR testing is routine nowadays; all lung adenocarcinoma samples go straight for EGFR detection by PCR.

EGFR non-mutated tumors also get tested for ROS1 and ALK mutations. In regard to ALK, we have recently switched to in-house immunohistochemistry instead of sending tissue to a reference lab for PCR. This is because ALK IHC results better correlate with treatment outcomes.

For melanomas, it has become routine, in Stage IV, to do BRAF by PCR. We prefer that method to immunohistochemistry because a PCR panel also covers the KIT mutation, thus providing oncologists with another target for treatment.

Recently, oncologists have started requesting molecular testing for gastrointestinal stromal tumors. Besides the usual KIT, these tissues get tested for PDGFRA

These are new aspects in cancer molecular diagnostic tests in the last 5 years.

What about the hematological malignancies, will it be of use in blood cancer as well?

Dr. Vladimir: I am not sure, as I am not a hematologist. In histopathology when we deal with diffuse large B cell lymphoma lymphomas use FISH to rule out “triple hit” (MYC, BCL2, and BCL6) lymphomas. But, as far as “druggable” mutations in other hematological malignancies are concerned, we do not get any such requests.

So, Doctor, moving forward, what do you think is the impact of this whole pandemic, in terms of the adoption of molecular diagnostic tests?

Dr. Vladimir: This pandemic has had no effect on what I do. I know that the pandemic has had a large effect on microbiology. What I use molecular testing for is completely different from the fast pace of a pandemic disease.

In general, do you think there is increased adoption of molecular testing during the pandemic or because of the pandemic?

Dr. Vladimir: In microbiology, yes.

Do you see some sort of innovation, or the use of point of care tests, or anything else coming up, especially because of the pandemic, either in anatomical pathology or in microbiology in general?

Dr. Vladimir: Again, not in anatomical pathology. As I have stated, in microbiology, there have been many advances and changes.

So, doctor kindly let us know what you think are the key challenges for a physician to order molecular diagnostic tests in cancer?

Dr. Vladimir: I think the only limitations are those imposed by the medical system. Does the patient have private insurance? Some drugs are not available in the public health care system, because of funding limitations.


The amount of immunohistochemistry that we use is probably the same as five years ago, but now we can do more with less; because now with two or three antibodies, you can clinch the diagnosis. For example, in lung cancers, we order just two stains. This tells us if it is squamous cell carcinoma or adenocarcinoma. If it is squamous, we do not order any molecular tests, however, if it is adenocarcinoma, we order EGFR.

So, doctor talking about pathology, as an anatomical pathologist, how do these molecular diagnostic tests help you? Where is the value addition for you?

Dr. Vladimir: The value, for anatomical pathologists, would be in better defining lymphomas, for example, triple hit cases with FISH, and in soft tissue sarcoma’s diagnosis, because most of them have some sort of known underlying mutation, that we can now test for. Other than that, molecular testing is not much help as far as the diagnosis is concerned, as we diagnose on the H & E slides. The thing that molecular testing does help is to determine the prognosis for the patient and to establish the best oncology treatment.

What do you think could be the upcoming trends in terms of molecular pathology in anatomical pathology?

Dr. Vladimir: It is mostly driven by oncologists. As far as the ability to diagnose disease is concerned, things have not changed dramatically for many decades. We have yet to discover a better way to diagnose disease. It is all glass slides, starting with H&E, then augmented by immunohistochemistry and on occasion fluorescent in situ hybridization.

However, the library is expanding. The amount of immunohistochemistry that we use is probably the same as five years ago, but now we can do more with less; because now with two or three antibodies, you can clinch the diagnosis. For example, in lung cancers, we order just two stains. This tells us if it is squamous cell carcinoma or adenocarcinoma. If it is squamous, we do not order any molecular tests, however, if it is adenocarcinoma, we order EGFR. Now, some patients with squamous would go to private, and the oncologists will request PD-L1. So, I do not think it will be much more molecular testing for diagnosis; it would be molecular for treatment, dictated by oncologists.

So, before we close doctor, if you have to leave us with a closing statement in terms of the molecular diagnostic space in New Zealand, what would that be?

Dr. Vladimir: I would say it is mostly driven by our oncology colleagues. As far as diagnosis, molecular testing is used rarely. Most of the molecular testing in anatomical pathology is done to identify targetable mutations, so our clinical colleagues can select the best inhibitors for cancer treatment.

Thank you very much for your time. Dr. Osipov.

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