PDF Issue 0617

53 Pages·2017·22.76 MB·English

JUNE 2017 # 31
In My View In Practice Profession Sitting Down With
Proteomics’ place in the Guidelines for How your brain makes RNA aficionado
fight against cancer molecular testing a diagnosis George Calin
13 30 – 32 46 – 48 50 – 51
Slides,
Sections
and Cells
The beautiful, intriguing
and informative art
of pathology

14 – 27
www.thepathologist.com
Nothing has changed,
except everything
Sanger sequencing and fragment analysis like you have never experienced
before. Same workflow, same trusted technology, now with an innovative all-
in-one cartridge that takes setup time from hours to minutes. Introducing the
Applied Biosystems™ SeqStudio™ Genetic Analyzer.
Find out more at thermofisher.com/seqstudio
For Research Use Only. Not for use in diagnostic procedures. © 2017 Thermo Fisher Scientific Inc. All rights reserved.
All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. COL21879 0517
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Case
of the
Month
Ovarian Mass

The hematoxylin-eosin-stained slides shown here were
prepared from a 20 cm mass, partially cystic and partially
solid, that was removed from the right ovary of a 59-year-old
female. Immunohistochemically, the tumor was positive for
napsin-A and PAX8, but negative for p53 and WT1.
What is the most likely diagnosis?
a High-grade serous carcinoma
b Clear cell carcinoma
c Mucinous cystadenocarcinoma
d Yolk sac tumor
Answer to last issue’s Case of the Month…
Nothing has changed, C. Kaposi sarcoma.
This tumor is composed of nodules of monomorphic spindle cells
except everything arranged in fascicles. Tumor cells form mitotic division figures
and include rare entrapped inflammatory cells and erythrocytes.
The expression of HHV-8 excludes other vascular neoplasms
from the differential. This is the classic variant of Kaposi sarcoma,
which has a predilection for the skin on the legs of elderly men.
Sanger sequencing and fragment analysis like you have never experienced Angiosarcoma favors the face and scalp and is composed of
widely infiltrative, hyperchromatic endothelial cells that form
before. Same workflow, same trusted technology, now with an innovative all-
crack-like vascular spaces and are negative for HHV-8.
in-one cartridge that takes setup time from hours to minutes. Introducing the
Applied Biosystems™ SeqStudio™ Genetic Analyzer.
Submitted by Garth Fraga, The University of Kansas, Kansas
City, USA.
To register your guess for this month‘s case, please go to http://tp.txp.to/0617/case-of-the-month
Find out more at thermofisher.com/seqstudio
We will reveal the answer in next month’s issue!
For Research Use Only. Not for use in diagnostic procedures. © 2017 Thermo Fisher Scientific Inc. All rights reserved.
All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. COL21879 0517 www.thepathologist.com
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Contents
30
03 Case Of The Month Upfront In My View
08 Small Samples; Big Promises 12 D-amino acids have not
07 Editorial historically been the focus of
Not With a Whimper 09 Minimalist Monitoring significant study – but that may
by Fedra Pavlou be changing. Tomonori Kimura
10 The ABCs of Autoimmunity points to their utility as biomarkers
for chronic kidney disease.
On The Cover 11 Parkinson’s Predictions
13 A ndreas Hühmer highlights the
JUNE 2017#31
A whole slide image of a importance of proteomics and
IPo1n2nro M–ctSThao 1a ae14nfnyo3 d– lncpmeV e2 aiiirib7ntecddehswf’a oop ue rlloatmCicgsfeauy itel,ni, v itlenSh ltear srewitga u cr intgi IGm2on9ou P–nli ed3rca5esuclitlnia cre e st efsotri n g PHa4 5rdo oi–waf 4eg 8ysnosoiuosrins brain makes SR5G0iNet –toA ir5ng 1agefi DCciaoolwninan d Wo ith parasagittal section of a the need to consider it alongside
human fetus. genomics to effectively advance the
www.thepathologist.com battle against cancer.
ISSUE 31 – JUNE 2017
Editor - Fedra Pavlou
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Publisher - Mark Goodrich
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50 Business Development Executive - Sally Loftus
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NextGen marc.bird@texer epublishing.com
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38 S lides in the Machine
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Whole slide images are huge, [email protected]
which can create storage and Digital Producer Web/Email - Peter Bartley
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sharing problems. But with
Digital Producer Web/App - Abygail Bradley
advances like cloud computing and [email protected]
Audience Insight Manager - Tracey Nicholls
machine learning, those obstacles
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are rapidly being overcome. Audience Project Associate - Nina Duffissey
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Traffic and Audience Associate - Lindsey Vickers
40 L iquid Assets
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What role does liquid biopsy Traffic Manager - Jody Fryett
Feature play in the future of cancer [email protected]
Social Media / Analytics Associate - Ben Holah
diagnosis and monitoring? Two
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14 S lides, Sections and Cells pioneers in the field share their Events Manager - Alice Daniels-Wright
Through the eyes of views on the pros, cons and [email protected]
Marketing Manager - Katy Pearson
pathologists, the world is a possibilities of the technique.
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fascinating and beautiful place. Financial Controller - Phil Dale
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a selection of images submitted
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by you – our readers – to reveal a Profession Chief Executive Officer - Andy Davies
glimpse of the world inside us… [email protected]
Chief Operating Officer - Tracey Peers
46 S olving the Mystery of
[email protected]
Medical Mistakes
Change of address:
Do you know what happens [email protected]
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pathology holds an increasingly The Center for RNA Interference
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not reflect the opinions of The Pathologist or its publishers, Texere Publishing.
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pathologists to get involved. Anderson Cancer Center, USA.
B
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Chicago, Illinois N O
O K

July 10-11 2017 W
3RD DIGITAL PATHOLOGY
CONGRESS: USA
Understanding and Utilizing Digital Pathology as a Tool for Advancing
Pathology Practice and Enabling Enhanced Patient Care
With the FDA, technology providers and hundreds of your peers in attendance, this event will
ensure you stay ahead of the curve. And what’s more – your pass is completely free!
Register for your free pass today:
www.global-engage.com/event/digital-pathology-usa/#register
SPEAKERS INCLUDE:
STEPHEN HEWITT SAMAR BETMOUNI DARIUSZ BORYS
Head, Experimental Pathology Director of Clinical Pathology, Associate Professor of Pathology
Laboratory, National Cancer University of Bradford, UK and Orthopaedic Surgery,
Institute, NIH Loyola University Medical Center
Follow Us
E: [email protected]
www.global-engage.com/event/digital-pathology-usa
@lifesciences_GE
B
O
Chicago, Illinois N O
O K
July 10-11 2017 W Not with a Whimper
Editorial
If you’re worried about the future of pathology, read on...
3RD DIGITAL PATHOLOGY
I
CONGRESS: USA
n June, I had the pleasure of visiting the oncology research
and treatment mecca that is the Memorial Sloan Kettering
Cancer Center, where I met with Michael Roehrl, Director
of the Precision Pathology Center – and one of our Power
List members. Our discussion took many twists and turns, but we
kept returning to one topic: the future. In particular, the need for
pathology to look forward and remain innovative and disruptive.
We spoke at length about the lack of pathology subspecialization
in Europe that is hindering progress and, worse still, good patient
care; the inhibitive fear of diagnostic error; the urgent need for
raised public awareness of pathology; the worrying acceptance of
budgetary and resource constraints; resistance to innovation (look
out for a follow-up article that I’ve already titled “Pathological
Complacency”); and other specialties’ critical dependence on
pathologists and laboratory physicians, whom Roehrl aptly calls
Understanding and Utilizing Digital Pathology as a Tool for Advancing the “Physicians’ Physician” (another article in the making...).
What struck me most during our conversation was Roehrl’s
Pathology Practice and Enabling Enhanced Patient Care passion for his profession, and the need for pathology to be a leader in
innovation in the era of precision health care, especially when it comes
to new technologies and disruptive theranostics. A challenge for
With the FDA, technology providers and hundreds of your peers in attendance, this event will pathology, he believes, has been predominantly caused by the reduced
ensure you stay ahead of the curve. And what’s more – your pass is completely free! finances allocated to it, the falling numbers of trainees attracted to it,
and sometimes a traditional mindset of those working within it. In
short, we agreed that we need more people fighting for pathology.
Register for your free pass today:
Though my colleagues and I have been fortunate to work with
www.global-engage.com/event/digital-pathology-usa/#register many trailblazers and advocates, there aren’t enough people who feel
sufficiently empowered to talk about the value of pathology to medical
colleagues, the budget controllers, government, the public and, dare
I say it, to patients. Just to emphasize the point, I was talking with
someone in industry recently who spoke of a customer – a very senior
SPEAKERS INCLUDE:
pathologist – who was normally openly communicative and articulate.
Apparently, he became less talkative as he ascended a building in an
elevator towards the floor containing the offices of C-suite executives
Reference where, on arrival, he “completely lost his voice.” We must acknowledge
1. JI López, “The Invisible Doctor”, that such failures in visibility come with consequences. I’ll refer you to
The Pathologist, 09, 46–48 (2015). one of many articles that we have published on the subject (1). If you
have any thoughts on this subject or if you would like to share your
opinion, we would love to hear from you ([email protected]).
I’ll leave you with a quote from a survey of medical students
that was presented at the 2017 annual congress of the Canadian
STEPHEN HEWITT SAMAR BETMOUNI DARIUSZ BORYS
Association of Pathologists: “Maybe you should take pathology out
Head, Experimental Pathology Director of Clinical Pathology, Associate Professor of Pathology
of the lecture titles so students aren’t put off.” We all need to work
Laboratory, National Cancer University of Bradford, UK and Orthopaedic Surgery,
together to change this perception.
Institute, NIH Loyola University Medical Center
Fedra Pavlou
Editor
Follow Us
E: [email protected]
www.global-engage.com/event/digital-pathology-usa www.thepathologist.com
@lifesciences_GE
8 Upfront
Upfront Small Samples; use, flexible to adjust, and can be used with
minimal DNA input.”
Big Promises What are the researchers doing with
the technique now? Ståhlberg outlines a
Reporting on research, number of clinical investigations applying
Ultrasensitive mutation
ultrasensitive mutation detection to liquid
innovations, policies and analysis could boost
biopsy, including patients with childhood
personalities that are liquid biopsy
sarcomas, melanomas and breast cancers.
shaping pathology today. He and his team are also applying their
It’s hard to look at a laboratory medicine approach to areas beyond cancer, including
Do you want to share journal without seeing the words “liquid chronic obstructive pulmonary disease and
biopsy” these days. Small wonder the immunological responses. Nonetheless, he
some interesting research
technique is such a hit – it’s simple, warns against jumping into liquid biopsy
or an issue that will noninvasive, and makes use of emerging too fast. “The potential of circulating cell-
impact pathology? molecular techniques to tell us more than free DNA is very high, but validation
ever about the diseases our patients face. studies are important to prove its clinical
But with all of these advantages, liquid value. You may find mutations without a
Email:
biopsy does face one challenge – sensitivity. disease – so we need to learn how and when
[email protected] “The main issue with analyzing to perform this type of analysis.”
circulating cell-free DNA is that its Ståhlberg next plans to learn exactly
concentration is low, and DNA of tumor which liquid biopsy applications gain the
origin is present at very low frequencies greatest clinical value from ultrasensitive
– sometimes only individual molecules,” mutation analysis. He and his colleagues
says Anders Ståhlberg, docent in molecular have recently received funding from
medicine at the University of Gothenburg’s several collaborating organizations to
Sahlgrenska Cancer Center. “Standard start a translational genomics platform
techniques are not sensitive enough to find (3) working with liquid biopsies and
these rare molecules,” he continues, “but ultrasensitive mutation analysis. And
with new approaches such as our SiMSen- he’s optimistic about the future of liquid
Seq technique, this is now possible.” biopsy: “By analyzing patient-specific
SiMSen-Seq allows the detection of mutations in blood plasma, we anticipate
circulating tumor DNA (ctDNA) in the improvements in diagnosis, treatment
blood with up to 1,000-fold more sensitivity selection, prognosis, treatment monitoring
than the methods currently in use. and relapse detection.” MS
Ståhlberg and his colleagues accomplish
this feat by adding a molecular barcoding References
step. “In molecular DNA barcoding, a 1. A Ståhlberg et al., “Simple multiplexed
unique sequence is added to each individual PCR-based barcoding of DNA for
DNA molecule that enables us to track all ultrasensitive mutation detection by
sequencing reads back to the original DNA next-generation sequencing”, Nat Protoc, 12,
molecule. By aligning reads with the same 664–682 (2017). PMID: 28253235.
barcode, it is then possible to differentiate 2. A Ståhlberg et al., “Simple, multiplexed,
between true mutations and those resulting PCR-based barcoding of DNA enables
from polymerase errors.” SiMSEn-Seq is sensitive mutation detection in liquid biopsies
not the only liquid biopsy method to use using sequencing”, Nucleic Acids Res, 44, e105
barcoding, but Ståhlberg says that each (2016). PMID: 27060140.
method carries its own limitations. “Our 3. “Translational Genomics Platform” (2017).
contribution is that we managed to develop Available at: http://bit.ly/2rMqmwi. Accessed
a cost-effective method that is simple to June 20, 2017.
Upfront 9
Minimalist
Monitoring
A new antibody-based
biosensor could facilitate
drug monitoring in resource-
poor areas
We are all well aware that patients in
developing countries urgently need access
to medications for chronic illnesses. But
a discussion we have far less frequently is
what happens once those patients receive
the treatments they need.
“Monitoring drug concentration in
patient blood is an important aspect
of medical treatment to improve the
efficiency of the drugs and decrease the
side effects,” says Lin Xue, a postdoctoral
scholar at École Polytechnique Fédérale
de Lausanne. But it’s easier said than
done; most monitoring calls for expensive
equipment and complex facilities that
may not be available in resource-poor
areas. Often, patients have to stay close
to the lab or hospital, infringing on their as drug concentrations increase, the What would such a sensor look
quality of life – and that’s if they’re able antibody preferentially binds to the like in the clinic? Ideally, as simple as
to access monitoring at all. Xue and drug, displacing the fluorescent ligand modern blood glucose meters, allowing
his colleagues recognized the need and causing the emission of a blue light patients to take a fingerprick sample
for affordable point-of-care detection instead. The result? A simple, measurable and use a handheld reader, perhaps in
of drug concentrations in blood and visual that indicates the amount of drug conjunction with a smartphone. In fact,
developed a biosensor molecule made present in a patient’s blood. Xue’s colleagues have already developed
up of three components (1): “The biosensors can be incorporated working prototypes of test strips and a
into paper-based point-of-care devices, reader, so the researchers are optimistic
1. An antibody fragment that can which are cheap, portable, time-saving that their device should be available in
bind the drug to be monitored, and easy to use. They could even be used the next few years. Ultimately, they’d
2. The light-producing enzyme by the non-experts, such as the patients also like to expand it; after all, says
luciferase, and themselves,” says Xue and emphasizes Xue, the need for monitoring doesn’t
3. A “tagging” molecule called that the system works with any antibody: stop at drug levels – he anticipates tests
SNAP-tag, which carries a “We can theoretically design antibody- for pathogens, hormones, vitamins, and
fluorescent ligand that the antibody based sensors towards an unlimited even biomarkers. MS
binds only when no drug is present. number of synthetic drugs.” And the
sensor’s performance was independent of Reference
In the absence of the drug, the antibody the antibody used – meaning that there’s 1. L Xue et al., “Bioluminescent antibodies for
and SNAP-tag bind, causing a reaction no costly, time-consuming optimization point-of-care diagnostics”, Angew Chem Int
called “bioluminescent resonance energy process needed to create a sensor for a Ed Engl, 56, 7112–7116 (2017). PMID:
transfer” that produces a red light. But new type of drug. 28510347.
www.thepathologist.com
10 Upfront
The ABCs of What do ABCs do?
“ABCs are present at high
Autoimmunity frequency in lupus-prone
mice,” says Rubtsova,
“and their appearance
A unique type of B cell
coincides with the
appears to play a role in the
onset of the disease
development of autoimmune
in these animals.”
disorders – and may explain the
The team also
disproportionate prevalence of
observed elevated
such diseases in women
ABCs in human
autoimmune disease
“It’s well-known that autoimmune patients – but at the
diseases mostly affect women – in fact, time, they weren’t sure
about 80 percent of all autoimmune whether the appearance
patients are women,” explains Kira of ABCs caused the
Rubtsova, a researcher and instructor development of disease
in biomedical science at National or merely coincided with it.
Jewish Health. “At the same time, In their recently published
the onset of autoimmunity usually study (2), Rubtsova’s team
happens during adulthood.” Why are generated mice that are predisposed
women so disproportionately affected to developing lupus-like autoimmunity,
by autoimmune issues? Rubtsova and but lack T-bet expression in B cells
her colleagues suspected that the female (meaning that they cannot generate development of novel therapies that
immune system undergoes changes ABCs). “We have followed the health could cure autoimmunity. Because our
with age that lead to the progression of conditions of these mice over time, results indicate that ABCs represent
autoimmunity – changes that the male comparing them with lupus-prone mice the pathogenic subset of cells, their
immune system does not experience. that can develop ABCs,” she says. In removal may lead to the amelioration
But precisely what are those changes? the absence of ABCs, the lupus-prone of disease.” One of her team’s next goals
In the quest to answer that question, mice were significantly less likely to is to develop a drug capable of depleting
Rubtsova’s research group discovered develop disease. “These data led us to or inactivating ABCs.
age-associated B cells (ABCs). the conclusion that ABCs drive the In the meantime, many questions
onset of autoimmunity.” remain. How do ABCs promote the
What are ABCs? development of autoimmunity? Why
“ABCs are a unique subset of B cells Could ABCs be diagnostically useful? is T-bet expression so critical for the
that can be distinguished from other “The presence of these cells can be used development of these cells? And why are
types by the expression of certain for diagnostic purposes,” Rubtsova says. females more predisposed to developing
molecules. In particular, ABCs express It’s possible that, one day, patients ABCs and autoimmune diseases? MS
the integrins CD11c and CD11b on suspected of autoimmune disorders could
their surfaces and contain high levels be tested for the presence of ABCs. And References
of transcription factor T-bet, none of if the cells participate in the disease 1. K Rubtsova et al., “Age-associated B cells: a
which is expressed by other types of process, it’s also possible that people at T-bet-dependent effector with roles in
B cells.” And when the researchers risk of developing such disorders might protective and pathogenic immunity”, J
compared the gene expression profiles even be screened using ABCs one day, Immunol, 195, 1933–1937 (2015). PMID:
of ABCs with those of other B cells, allowing doctors to spot autoimmune 26297793.
they found hundreds of differentially diseases before symptoms arise. 2. K Rubtsova et al., “B cells expressing the
expressed genes – indicating that ABCs But Rubtsova also wants to highlight transcription factor T-bet drive lupus-like
have a unique phenotype and likely a the therapeutic potential: “These autoimmunity”, J Clin Invest, 127, 1392–
unique function (1). cells can be used as targets for the 1404 (2017). PMID: 28240602.