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Wednesday 19 June 2013

Marker for NSCLC Chemo Response Doesn't Hold Up (CME/CE)

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By Crystal Phend, Senior Staff Writer, MedPage Today Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse PlannerA DNA repair biomarker thought to predict benefit from platinum-based chemotherapy in non-small cell lung cancer (NSCLC) doesn't actually do that good a job.Point out that the problem appeared to be both technical and due to the inability of the assay to distinguish the key form of the protein for DNA repair.

A DNA repair biomarker thought to predict benefit from platinum-based chemotherapy in non-small cell lung cancer (NSCLC) doesn't actually do that good a job, a validation study showed.

The ERCC1 protein expression level didn't predict a boost in overall survival (OS) from adjuvant cisplatin (Platinol)-based chemotherapy compared with observation alone in two clinical trials (P=0.23 for interaction), Jean-Charles Soria, MD, PhD, of Institut Gustave-Roussy in Villejuif, France, and colleagues found.

In fact, any hint of utility in distinguishing chemotherapy response actually came from the ERCC1-positive group, rather than the ERCC1-negative group as suggested in the initial trial proposing the protein as a predictive biomarker.

The problem appeared to be both technical and due to the inability of the assay to distinguish the key form of the protein for DNA repair, the group reported in the March 21 issue of the New England Journal of Medicine.

"Currently available antibodies do not have adequate discrimination for therapeutic decision making regarding cisplatin-containing treatment in patients with NSCLC, which requires the specific detection of the unique functional isoform of ERCC1 -- ERCC1-202," they wrote.

The other three isoforms of ERCC1 (excision repair cross-complementation group 1) protein aren't as critical in fighting the cytotoxic effect of platinum chemotherapy.

However, the isoforms are so similar in shape that manufacturing a specific antibody that could pick out only ERCC1-202 would be a daunting challenge, Grace Dy, MD, of Roswell Park Cancer Institute in Buffalo, N.Y., explained in an interview.

"That does not mean that ERCC1 itself is totally useless," she told MedPage Today. But "it is a reminder to us that getting a biomarker validated and tested is a tortuous and difficult path."

The researchers agreed that another route may have to be found to make use of ERCC1 as a biomarker for platinum chemotherapy response.

Most trials looking at ERCC1 expression in NSCLC, since the initial demonstration of its predictive value in a subanalysis of the International Adjuvant Lung Cancer Trial (IALT), has used immunohistochemistry with a mouse monoclonal antibody.

But no consensus has been reached for the best was to evaluate ERCC1 expression, Soria's group noted.

"Functional assays may be required to detect an authentic prognostic influence of DNA repair proteins," they concluded.

They dug into the specifics of the immunohistochemistry method by analyzing a validation set of samples from 494 patients in two independent phase III trials -- the National Cancer Institute of Canada Clinical Trials Group JBR.10 and the Cancer and Leukemia Group B 9633 trial from the Lung Adjuvant Cisplatin Evaluation Biology project.

Those trials did not confirm any OS advantage from adjuvant platin-based chemotherapy versus no chemotherapy controls among tumors that stained negative for ERCC1, with a mortality hazard ratio of 1.16 that wasn't even close to statistical significance (P=0.62).

Also contrary to what would have been expected from the IALT results, there was some hint of chemotherapy benefit within the ERCC1-positive group. The HR of death from any cause was 0.78 versus controls, although still not a statistically significant trend (P=0.09).

To see what might be behind these differences, the researchers re-analyzed the original IALT Biology subanalysis.

Repeat staining of the entire set of tumor-block samples indicated a big shift in ERCC1 status, with 78% scoring positive compared with the reported 44%.

That changed the results too, with ERCC1 no longer a predictive biomarker for OS benefit from chemotherapy (P=0.53 for interaction).

The validation study used a different batch of the mouse antibody than used in 2006 in the original study.

But different cutoffs for positivity didn't improve prediction, the researchers noted.

Testing 14 other commercially-available monoclonal antibodies for ERCC1 detection indicated that none were specific for only one isoform; all responded the same to at least three of the four isoforms.

Quantitative real time-PCR analysis of mRNA levels of ERCC1 could distinguish response to two isoforms -- the key 202 isoform plus 204 -- but didn't prove to be any more predictive of platin chemotherapy response.

The researchers suggested this as one explanation for their results because "such cross-reactivity could introduce unexpected variability in staining in validation studies" and "lead to potential artifacts, with discrepant results."

The study was supported by an unrestricted grant from Eli Lilly and by grants from Institut National du Cancer Programme National d'Excellence Spécialisé and Programme Hospitalier de Recherche Clinique; by La Ligue Nationale contre le Cancer and an unrestricted grant from sanofi-aventis; by a contract from the European Union Seventh Framework Program under a grant agreement; and by a translational research fellowship from Roche.

Soria reported grants to his institution from Eli Lilly and sanofi-aventis and being named on a patent regarding ERCC1 expression in predicting response for cancer chemotherapy, although without any revenues to him or his institution.

Crystal Phend

Staff Writer

Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical Post, Oncology Times, Doctor's Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.

Less Invasive Autopsy Works Nearly as Well (CME/CE)

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By Todd Neale, Senior Staff Writer, MedPage Today Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse PlannerA minimally invasive approach using postmortem MRI may represent a viable alternative to a conventional autopsy in fetuses, children, and teens.Note that the concordance between whole-body MRI and postmortem exam was greatest in fetuses and declined with increasing age among the children.

A minimally invasive approach using postmortem MRI may represent a viable alternative to a conventional autopsy in fetuses, children, and teens, researchers found.

In fetuses and individuals 16 and younger, a minimally invasive autopsy that included MRI identified the same cause of death or major pathological abnormality that a conventional autopsy did in 89.3% of cases, according to Sudhin Thayyil, PhD, of University College London, and colleagues.

The concordance was greatest in fetuses and declined with increasing age among the children, the researchers reported online in The Lancet.

"Thus, minimally invasive autopsy could be a suitable alternative to conventional autopsy for detection of cause of death or major pathological lesions in selected cases for which an invasive postmortem examination is unacceptable," they wrote.

It is important to closely involve parents in the process of establishing a minimally invasive autopsy program, "and contrary to popular belief, bereaved parents often view this involvement positively," they added. "Future studies should examine the clinical, psychological, epidemiological, and economic effect of minimally invasive autopsy."

In recent years, rates of autopsy have fallen in developed countries for a variety of reasons, including objection by the families of the deceased.

Some studies have evaluated postmortem MRI as a more acceptable alternative to conventional autopsy, but there is limited evidence regarding its accuracy.

In the current prospective study performed at two London centers, Thayyil and colleagues compared autopsy performed using postmortem, whole-body MRI with or without other minimally invasive tools with that performed by conventional means for 400 cases -- 69% were fetuses and 31% were children 16 or younger.

The average time from death or delivery and the postmortem MRI was 4.5 days. The images were interpreted by pediatric radiologists -- one each for the nervous, cardiovascular, pulmonary and abdominal, and musculoskeletal body systems for each case.

Compared with conventional autopsy, the accuracy of the minimally invasive approach for identifying the cause of death or a major pathological change varied according to the age of the cases: 94.6% for fetuses at 24 weeks of gestation or less95.7% for fetuses at more than 24 weeks of gestation81% for newborns 1 month or younger84.9% for infants age 1 month to 1 year53.6% for children older than 1 year

"The lower concordance in children than fetuses was mainly due to undetected pneumonia and myocarditis," the researchers noted.

"This finding is expected, and is almost certainly related to the changing pattern of underlying pathological changes associated with autopsy across this age range, from mostly structural anomalies in fetuses to mostly infective causes in infancy and older children," they wrote.

A radiologist and a pathologist who did not know the results of the autopsy used a set of predefined criteria to determine whether the minimally invasive approach would have been sufficient for each case; they determined that a full autopsy might not have been necessary in 41% of cases. The minimally invasive and conventional approaches yielded similar findings in 99.4% of those cases.

The authors acknowledged some limitations of the analysis, including the uncertain applicability to less specialized settings, the inclusion of only those cases for which consent for conventional autopsy was obtained, and the lack of information on the economic aspects of postmortem MRI.

"Although minimally invasive autopsy can be less expensive than conventional autopsy, the overall cost of postmortem services might rise because parents who decide against autopsy might want a minimally invasive autopsy, which paradoxically increases the workload for both pathologists and radiologists," Thayyil and colleagues wrote.

Despite those limitations, however, the researchers "have presented a starting point for development of a robust system for postmortem diagnosis using various modalities (i.e., pathology, radiology, laboratory testing) and a system of interdisciplinary consultation and collaborative diagnosis, mimicking systems for optimum diagnostic assessment of living patients," according to Corinne Fligner, MD, and Manjiri Dighe, MD, both of the University of Washington in Seattle.

"Some deaths could be assessed with minimally invasive autopsy," they wrote in an accompanying editorial, "but some investigations will mandate use of conventional autopsy."

The paper is an independent report commissioned and funded by the Policy Research Program in the U.K. Department of Health. The study was also supported by grants from the British Heart Foundation, Wellbeing of Women and Stillbirth and Neonatal Death charities, and Foundation for the Study of Infant Deaths.

Thayyil has received a Clinician Scientist Award from the National Institute for Health Research. His co-authors reported support from the National Institute for Health Research, the Foundation Leducq, the Higher Education Funding Council for England, and the Great Ormond Street Hospital for Children NHS Foundation Trust Charity.

The study authors and the editorialists reported that they had no conflicts of interest.

Todd Neale

Senior Staff Writer

Todd Neale, MedPage Today Staff Writer, got his start in journalism at Audubon Magazine and made a stop in directory publishing before landing at MedPage Today. He received a B.S. in biology from the University of Massachusetts Amherst and an M.A. in journalism from the Science, Health, and Environmental Reporting program at New York University.

Gene Studies Suggest New Tx for Endometrial Cancer (CME/CE)

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By Charles Bankhead, Staff Writer, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse PlannerEndometrial cancers have been broadly classified into two groups: Type I endometrioid tumors with favorable prognosis and type II, primarily serous, tumors that have a worse outcome and different treatment approaches.This study proposes a reclassification of endometrial carcinoma which may affect therapy.

A comprehensive molecular analysis separated endometrial cancers into four distinct subtypes that have the potential to influence decision making about adjuvant therapy, investigators reported.

The analysis allowed scientists to categorize the cancers as microsatellite instability hypermutated, copy-number low, copy-number high, and a previously unrecognized subset of high-grade endometrioid tumors -- POLE ultramutated -- that have a molecular phenotype similar to that of uterine serous carcinomas.

Given that early serous-type uterine cancers are usually treated by chemotherapy and early endometrioid cancers by radiotherapy, the reclassification resulting from the analysis suggests a need to rethink treatment and clinical trial strategies, the researchers wrote online in Nature.

"The compelling similarities between this subset of endometrioid tumors and uterine serous carcinomas suggest that genomic-based classification may lead to improved management of these patients," Douglas A. Levine, MD, of Memorial Sloan-Kettering Cancer Center in New York City, and co-authors concluded.

"Clinicians should carefully consider treating copy-number-altered endometrioid patients with chemotherapy rather than adjuvant radiotherapy and formally test such hypotheses in prospective clinical trials. Furthermore, the marked molecular differences between endometrioid and serous-like tumors suggest that the tumors warrant separate clinical trials to develop the independent treatment paradigms that have improved outcomes in other tumor types, such as breast cancer."

Historically, endometrial cancer has been divided into two classifications: type I endometrioid and type II serous. The former is associated with estrogen excess, obesity, hormone-receptor positivity, and more favorable prognosis. Type II cancers occur more often in older, non-obese women and are associated with worse prognosis.

Recent studies have identified new characteristics that might further distinguish type I and type II tumors, the authors noted in their introduction. Most of the observations have come from studies of type I cancers and include early occurrence of PTEN mutations, co-occurrence with other mutations in the PI3K/AKT pathway, and microsatellite instability in about one third of the tumors.

Studies of type II tumors have show that microsatellite instability is an infrequent occurrence and that mutations in TP53, PIK3CA, and PPP2R1A occur frequently.

Previous studies have been limited to DNA sequencing of heterogeneous samples. Levine and colleagues in the Cancer Genome Atlas Research Network performed a more comprehensive, multiplatform analysis of low- and high-grade endometrioid tumors and serous uterine carcinoma designed to provide more insight into molecular basis of uterine cancer.

The analysis involved specimens and germline DNA from 373 patients: 307 with endometrioid tumors, 53 with serous tumors, and 13 with mixed histology.

The investigators performed multiples tests on varying fractions of the specimens/DNA, including somatic copy number alterations; exome sequence analysis; subtype classification via expression of messenger RNA, protein, and microRNA, and DNA methylation; somatic chromosomal (structural) aberrations; and pathway alterations. They also compared clinical/pathologic features of uterine serous carcinoma to those of serous ovarian and basal-like breast cancers.

Broadly speaking, the analysis showed that serous tumors and about one fourth of high-grade endometrioid tumors had extensive copy number alterations, few DNA methylation changes, low estrogen/progesterone receptor levels, and frequent TP53 mutations.

Most of the remaining endometrioid tumors had few copy number alterations or TP53 mutations, but frequently harbored mutations in PTEN, CTNNB1, PIK3CA, ARID1A, and KRAS. Investigators also found novel mutations in the SWI/SNF chromatin remodeling-gene ARID5B.

A subset of endometrioid tumors frequently harbored transversion mutations and newly identified hotspot mutations in POLE, which were associated with worse prognosis.

Levine and colleagues found that uterine serous carcinoma shared many molecular features with high-grade serous ovarian carcinoma and basal-like breast carcinoma, despite having more mutations. The observation suggests opportunities for overlapping treatment strategies, they said.

The results make a compelling argument in favor of broadening the classification system for uterine cancer to improve diagnostic precision and to guide selection of treatment for uterine cancer, according to Thanh Dellinger, MD, of City of Hope in Duarte, Calif.

“We have been treating uterine cancers based essentially on histopathologic criteria. This model is really outdated. This kind of two-tier classification really has not helped us out,” she said. “We need to predict who should receive radiation and who should receive chemotherapy. We really need a new, more personalized approach of molecular assays to identify genetic aberrations to predict who will do well, who will live longer, what type of therapy they should receive.”

The findings derived from the Cancer Genome Atlas Research Network are an important first step “in the right direction,” Dellinger added.

UPDATE: This article, originally published May 2, 2013 at 8:07 a.m. was updated with new material at 1:01 p.m.

The Cancer Genome Atlas Research Network is supported by the National Institutes of Health.

The authors reported no competing interests.

Charles Bankhead

Staff Writer

Working from Houston, home to one of the world's largest medical complexes, Charles Bankhead has more than 20 years of experience as a medical writer and editor. His career began as a science and medical writer at an academic medical center. He later spent almost a decade as a writer and editor for Medical World News, one of the leading medical trade magazines of its era. His byline has appeared in medical publications that have included Cardio, Cosmetic Surgery Times, Dermatology Times, Diagnostic Imaging, Family Practice, Journal of the National Cancer Institute, Medscape, Oncology News International, Oncology Times, Ophthalmology Times, Patient Care, Renal and Urology News, The Medical Post, Urology Times, and the International Medical News Group newspapers. He has a BA in journalism and MA in mass communications, both from Texas Tech University.

New Immune Disease Cripples White Cells (CME/CE)

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By Crystal Phend, Senior Staff Writer, MedPage Today Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse PlannerA newly-described immunodeficiency syndrome of neutrophil defects, bone marrow fibrosis, nephromegaly, and life-threatening infections arises from a genetic mutation that impairs movement of proteins within cells.Note that although the disorder is rare, the findings may have some broader implications by revealing more about the inner workings of the immune system.

A newly-described immunodeficiency syndrome of neutrophil defects, bone marrow fibrosis, nephromegaly, and life-threatening infections arises from a genetic mutation that impairs movement of proteins within cells, researchers found.

All seven affected children studied had homozygous mutations in VPS45, which encodes for a protein that regulates intracellular traffic of proteins through the endosomal system, Raz Somech, MD, PhD, of Israel's Tel Aviv University, and colleagues reported online in the New England Journal of Medicine.

Putting normal VPS45 genetic material into patient cells ex vivo fixed the migration defect and cut down on neutrophil apoptosis.

"VPS45 deficiency should be considered in patients with neutropenia, bone marrow fibrosis, nephromegaly, migration defects, and severe bacterial and fungal infections," the group wrote.

While the disorder is rare, the findings may have some broader implications by revealing more about the inner workings of the immune system, Somech and colleagues suggested.

Neutrophils play a particularly important role in fighting bacterial and fungal infections, in part by secreting proteins stored in specialized vesicles and fusing membrane compartments to kill ingested microbes.

A variety of other immunodeficiencies involving defective neutrophils have been described, with a range of mechanisms.

"The cellular defects in this new disease suggest that other immunodeficiency disorders may also result from impaired vesicle trafficking," Somech's group noted.

They studied seven children from five Palestinian families of common ancestry who presented in infancy with poor weight gain, enlarged livers and spleens, and severe infections or deep-seated abscesses.

The children also had neutropenia that didn't respond to high-dose recombinant granulocyte colony-stimulating factor and bone marrow fibrosis.

Two siblings in one of the families also had delayed neurologic development, hearing loss, and cortical blindness, but it wasn't clear whether those problems related to the VPS45 mutation or some other genetic abnormality.

Two of the children died from infection after failed hematopoietic stem-cell transplantation; three died before the procedure could be done.

Parents and unaffected siblings were healthy with normal blood counts and neutrophil function.

A search for the causative gene using homozygosity mapping with single-nucleotide polymorphism arrays, whole-exome sequencing, immunoblotting, immunofluorescence, electron microscopy, a real-time quantitative polymerase-chain-reaction assay, immunohistochemistry, flow cytometry, fibroblast motility assays, and measurements of apoptosis turned up the following: Homozygous mutation on VPS45 in Thr224Asn or Glu238LysReduced levels of VPS45 protein and its binding partners rabenosyn-5 and syntaxin-16Lower ß1 integrin levels on the surface of VPS45-deficient neutrophils and fibroblastsImpaired motility and increased apoptosis in VPS45-deficient fibroblasts

The mutations weren't found in 250 ethnically-matched controls or in normal genome and exome databases.

"The absence of dysmorphic features such as albinism or short stature distinguishes this syndrome from other known syndromes associated with neutropenia, such as the Chédiak–Higashi syndrome, Griscelli's syndrome type 2, the Hermansky-Pudlak syndrome type 2, and p14 deficiency," the researchers noted.

The study was supported by the National Human Genome Research Institute, an advanced grant (EXPLORE) from the European Research Council, the Gottfried-Wilhelm-Leibniz Program of the Deutsche Forschungsgemeinschaft, the Care-for-Rare Foundation, and the German Network on Primary Immunodeficiency Diseases.

Somech reported grants from the Israeli Ministry of Health, Israeli Science Foundation, and Jeffrey Modell Foundation.

Crystal Phend

Staff Writer

Study Shows ID Errors in Prostate Biopsies (CME/CE)

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By Charles Bankhead, Staff Writer, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse PlannerThis study prospectively evaluated in routine clinical practice, the frequency of occult type 1 provenance errors (complete transposition between patients) and type 2 provenance errors (contamination of the target patient's tissue with that of one or more unrelated patients) among a number of urology practices and surgical pathology laboratories.Note that the study suggests that prospective DNA testing to confirm the identity of prostate biopsies that show adenocarcinoma may be useful for preventing treatment errors stemming from misidentification.

As many as 3.5% of prostate biopsy specimens were contaminated or inadvertently switched with that of another patient, according to a review of 13,000 samples from 54 laboratories.

The overall error rate was less than 1%, but rates among different types of labs ranged as high as 3.51%. No laboratory included in the study had an error-free performance record.

Institutional approval for the study required investigators to remove all identifying information from the specimens. Consequently, the impact of the laboratory errors could not be assessed, as reported online in the American Journal of Clinical Pathology.

"It is possible that in a subset of cases, the adenocarcinoma from the foreign patient that was the source of the extraneous tissue exhibited sufficiently similar characteristics of the target patient such that either patient's diagnosis would have resulted in the same course of therapy," John D. Pfeifer, MD, PhD, and Jingxia Liu, PhD, of Washington University in St. Louis, wrote of their findings.

"Regardless of the portion of cases in which patients may have, by chance, received the correct treatment despite the specimen identity error, the fact remains that ... a diagnosis was assigned to the wrong patient with no knowledge or even suspicion of the error that had occurred."

The study examined the frequency of occult "specimen provenance complications" (SPCs), errors that occur without any indication of a problem. SPCs arise when specimens are matched to the wrong patients (type 1 error) or when one patient's specimen is contaminated by tissue from one or more other patients (type 2 error).

SPCs have obvious implications for patient safety and medicolegal actions, the authors noted in their introduction. However, the frequency with which these errors occur has remained unclear.

To describe the rates of both types of SPCs, Pfeifer and Liu analyzed data for 13,000 prostate biopsy specimens obtained in routine clinical practice. The specimens were processed by a variety of surgical pathology and urology group practice laboratories.

Data for the study came from Strand Analytical Laboratories, an Indianapolis company that has developed a DNA-based test for occult SPCs. The test employs short tandem repeat (STR) analysis, originally developed by the FBI.

"STR analysis has been shown to be particularly useful in identifying occult specimen identity errors," the authors noted in their introduction.

The investigators grouped the 54 laboratories into five categories based on work flow, location, and management structure: physician-owned labs within a group-practice setting, independent reference labs, hospital labs, nonphysician owned labs located in facilities shared with group practices, and labs that have the technical histopathology and professional pathology in separate facilities, necessitating transport of specimen slides.

The error rate for all labs combined was low: 0.26% for type 1 errors and 0.67% for type 2 errors. However, the authors pointed out, each SPC involved at least two patients, "the target patient and the foreign patient (or patients) whose tissue was misidentified as originating from the target patient."

Reference laboratories had the highest rate of SPCs: 0.37% for type 1 and 3.14% for type 2, resulting in an overall error rate of 3.51%.

Only one clinical trial has attempted to document SPCs, according to the authors. The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial took steps to measure the rate of SPCs after three cases of occult biopsy specimen misidentification occurred during the first 2 years.

The rate of type 1 errors was 0.4% during the first 2 years of the REDUCE trial and declined to 0.02% in the final 2 years, after investigators implemented changes in specimen-handling procedures. A type 1 error rate of 0.5% persisted throughout the trial for blood samples that served as reference specimens.

Based on their study, the authors suggested that prospective DNA testing to confirm the identity of prostate biopsies that show adenocarcinoma may be useful for preventing treatment errors stemming from misidentification.

Strand Analytical Laboratories, which developed a test for STR analysis, provided the data for the study.

The authors had no relevant disclosures.

Charles Bankhead

Staff Writer

Gene Patents Spark Debate in High Court

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By David Pittman, Washington Correspondent, MedPage Today

WASHINGTON -- Supreme Court justices lobbed hard questions Monday about whether a company could patent isolated human genes in a case that looms large in the personalized medicine arena.

During arguments before the court, several justices expressed doubt that Myriad Genetics could rightfully patent segments of human genes BRCA1 and BRCA2, genes in which mutations are indications of increased risk of breast and ovarian cancer.

Products of nature aren't patentable. Only inventions are, but Salt Lake City-based Myriad argued that because the genes have been isolated from the body, they are no longer a product of nature and can be patented.

"Now, yes, you can have a patent on the process of extracting that small part, but I don't understand how a small part of something bigger isn't obvious," Chief Justice John Roberts said.

Meanwhile, Myriad can stop others from making, using, selling, and offering to sell genetic testing to determine if an individual has such a genetic mutation.

A number of organizations including those led by physicians, researchers, clinicians, and other health professions were initially involved in the case.

"There might be a million things you can do with the BRCA genes, but nobody but Myriad is allowed to look at it and that's impeding science rather than advancing it," Christopher Hansen, who argued against Myriad, said.

A district court in 2010 ruled the patents invalid because they were products of nature. The Court of Appeals for the Federal Circuit in 2011 disagreed, setting up the case for the Supreme Court.

The Federal Circuit likened Myriad's case to that of a baseball bat. A tree isn't patent eligible, but a bat -- once extracted from the tree and carved -- is eligible.

Roberts disagreed with that analogy. "The baseball bat is quite different," Roberts said. "You don't look at a tree and say, 'well, I've cut the branch here and cut it here and all of a sudden I've got a baseball bat.' You have to invent it, if you will."

Justices repeatedly turned to the analogy of extracting a molecule from a tree leaf that is known for medicinal use. The leaf itself is a product of nature and not patentable, but the extracted molecule may be, Justice Samuel Alito said, seeming to support Myriad.

"The isolated DNA has a very different function than the DNA as it exists in your body," he added, just like the extracted molecule and the leaf. "And although the chemical composition may not be different, it certainly is in a different form."

Justice Sonia Sotomayor took a different tact and said the genes might be obvious -- not novel -- and therefore not patentable, which is a different argument from saying the genes are found in nature and not patent eligible.

Justice Stephen Breyer said he supported allowing companies like Myriad to be able to patent the process by which they find and extract certain gene segments -- just not genes themselves.

"It's important to keep products of nature free of the restrictions that patents there are," Breyer said.

The U.S. Patent and Trademark Office has issued thousand of patents similar to that of Myriad's BRCA1 and BRCA2 and the company argued that a ruling against it could mean less investment in the field if they and others can't protect their work -- an argument justices questioned.

"What does Myriad get out of this deal? Why shouldn't we worry that Myriad or companies like it will just say, well, you know, we're not going to do this work anymore?" Justice Elena Kagan asked.

The High Court could rule in the case -- Association for Molecular Pathology v. Myriad Genetics -- before its current term ends in late June.

David Pittman

David Pittman is MedPage Today’s Washington Correspondent, following the intersection of policy and healthcare. He covers Congress, FDA, and other health agencies in Washington, as well as major healthcare events. David holds bachelors’ degrees in journalism and chemistry from the University of Georgia and previously worked at the Amarillo Globe-News in Texas, Chemical & Engineering News and most recently FDAnews.

Wednesday 19 June 2013

Marker for NSCLC Chemo Response Doesn&apos;t Hold Up (CME/CE)

Less Invasive Autopsy Works Nearly as Well (CME/CE)

Gene Studies Suggest New Tx for Endometrial Cancer (CME/CE)

New Immune Disease Cripples White Cells (CME/CE)

Study Shows ID Errors in Prostate Biopsies (CME/CE)

Gene Patents Spark Debate in High Court

Marker for NSCLC Chemo Response Doesn't Hold Up (CME/CE)