Biomarkers accurately distinguish mesothelioma from non-cancerous tissue

Philadelphia, PA – Scientists have identified four biomarkers that may help resolve the difficult differential diagnosis between malignant pleural mesothelioma (MPM) and non-cancerous pleural tissue with reactive mesothelial proliferations (RMPs). This is a frequent differential diagnostic problem in pleural biopsy samples taken from patients with clinical suspicion of MPM. The ability to make more accurate diagnoses earlier may facilitate improved patient outcomes. This new study appears in the Journal of Molecular Diagnostics.

“Our goal was to identify microRNAs (miRNAs) that can aid in the differential diagnosis of MPM from RMPs,” says lead investigator Eric Santoni-Rugiu, MD, PhD, of the Laboratory of Molecular Pathology at the Department of Pathology of Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. miRNAs, which are small, non-coding RNA strands composed of approximately 22 nucleotides, have been shown to be potential diagnostic, prognostic, and predictive markers in other cancers.

Copenhagen University Hospital, Herlev

After screening 742 miRNAs, the investigators identified miR-126, miR-143, miR-145, and miR-652 as the best candidates to diagnose MPM. Using results from these four miRNAs, tissue samples from patients with known outcomes could be classified as MPM or non-cancerous with an accuracy of 0.94, sensitivity of 0.95, and specificity of 0.93. Further, an association between miRNA levels and patient survival could be made.

“The International Mesothelioma Interest Group (IMIG) recommends that a diagnostic marker of MPM have sensitivity/specificity of >0.80, and these criteria are fulfilled by our miRNA classifier,” comments Dr. Santoni-Rugiu. The authors suggest that diagnostic accuracy can be further improved by adding immunohistochemical testing of miRNA targets in biopsy tissue to their miRNA assay. This combined assay could enable analysis of samples with low tumor cell count.

MPM, which is linked to long-term asbestos exposure, is an aggressive cancer originating from the mesothelial cells that line the membrane surrounding each lung, known as the pleura. Distinguishing MPM from noncancerous abnormalities, such as reactive mesothelial hyperplasia or fibrous pleurisy (organizing pleuritis), can be challenging as there are no generally accepted diagnostic biomarkers for differentiating these two conditions. As a result, patients often present with the disease when they are already at an advanced stage, and less than 20% of patients can be successfully treated surgically.

The current study, however, suggests that miRNAs may provide new opportunities for improving the accuracy of the differential diagnosis between MPM and noncancerous pleural conditions. If further validated, the combination of ISH for miRNAs with immunohistocemical testing of miRNA targets may therefore have the potential to aid in the diagnosis, and thus outcome, of MPM.

- MFP News Services
- 7-25-14

HIV Researchers Dead in Ukraine Air Crash

By Ed Susman

MELBOURNE, Australia — When I started covering the AIDS epidemic in the 1980s, among the first researchers who would explain the efforts to beat the disease was Joep Lange, MD, professor of medicine at the Academic Medical Center, Amsterdam.

foto joep lange_width200px

He helped me comprehend the disease, how it spreads, how it could be controlled, and the need for passion and positive political action. That kind, compassionate voice was silenced Thursday when his plane was shot down by a missile over war-torn Ukraine. He was among the 298 people who were killed.

The Malaysian Airlines Flight 17 was flying at 33,000 feet over disputed territory when a missile brought down with such ferocity and suddenness that the flight crew could not muster a distress call.

International AIDS Society officials say they have confirmed that 6 people on the way to the conference were on MH17. Speculation about vast numbers of conference- bound attendees appears to have been over-stated.

Dr. Lange and the other HIV/AIDS researchers were en route to Melbourne for the 20th International AIDS Conference. Dr. Lange served as president of the International AIDS Society, which sponsors the conference, in 2004 when it was held in Bangkok, Thailand.
In an official statement, the IAS said:
“The International AIDS Society today expresses its sincere sadness at receiving news that a number of colleagues and friends en route to attend the 20th International AIDS Conference taking place in Melbourne, Australia, were on board the Malaysian Airlines MH17 flight that has crashed over Ukraine earlier today.
“At this incredibly sad and sensitive time the IAS stands with our international family and sends condolences to the loved ones of those who have been lost to this tragedy.”

Academic Medical Center - Amsterdam

Friends and colleagues of Dr. Lange went to social media to eulogize their lost colleague:
‘‘He was a kind man and a true humanitarian,’’ tweeted Seema Yasmin, MD, professor of public health at the University of Texas at Dallas. ‘‘How do we measure how much a person has done for humanity? People like Joep change the course of epidemics.’’
She said that Dr. Lange personally helped her make her decision to attend medical school. Dr. Lange was the father of 5 girls. Yasmin tweeted: “I asked him why he worked so much. He said “Do you know how much it costs to buy shoes for 5 girls?”
UN AIDS executive director Michael Sidibé tweeted: “My thoughts & prayers to families of those tragically lost on flight #MH17. Many passengers were en route to #AIDS2014 here in #Melbourne.” In addition to Dr. Lange and his partner, Jacqueline van Tongeren, and WHO representative Glenn Thomas, 3 AIDS actinides were also traveling on MH17: Lucie van Mens, Pim de Kuijer, and Maria Adriana de Schutter.

The tragedy recalls another airline catastrophe which took the life of prominent AIDS researcher Jonathan Mann. He was aboard Swissair 111 that plunged into Peggys Cove, off the coast of Nova Scotia on Sept. 2, 1998 – scarcely 6 weeks after another International AIDS Society meeting in Geneva, Switzerland.
Mann was an administrator for WHO and was returning to his office on the doomed aircraft. . In addition to Mann and his wife, Mary-Lou Clements-Mann, also an AIDS researcher, 227 other people lost their lives on Swissair 111. An uncontrolled on-board fire was determined to be the cause of the loss of the MD-11 aircraft.
Eerily, I had flown to Geneva on that same Swissair flight number 111 as did many other participants in that meeting in late July.

- MFP News Servies
- 7-18-14

Moles Linked to Possible Risk for Breast Cancer

Cutaneous nevi, commonly known as moles, may be a novel predictor of breast cancer, according to two studies recently published PLOS Medicine. Jiali Han and colleagues from Indiana University and Harvard University, United States, and Marina Kvaskoff and colleagues from INSERM, France, report that women with a greater number of nevi are more likely to develop breast cancer.

Indiana University

The researchers reached these conclusions by using data from two large prospective cohorts– the Nurses’ Health Study in the United States, including 74,523 female nurses followed for 24 years, and the E3N Teachers’ Study Cohort in France, including 89,902 women followed for 18 years.

In the Nurses’ Health Study, Han and colleagues asked study participants to report the number of nevi >3mm on their left arm at the initial assessment. They observed that women with 15 or more nevi were 35% more likely to be diagnosed with breast cancer than women who reported no nevi, corresponding to an absolute risk of developing breast cancer of 8.48% in women with no nevi and 11.4% for women with 15 or more nevi. In a subgroup of women, they observed that postmenopausal women with six or more nevi had higher blood levels of estrogen and testosterone than women with no nevi, and that the association between nevi and breast cancer risk disappeared after adjustment for hormone levels.

In the E3N Study, including mostly teachers, Kvaskoff and colleagues asked study participants to report whether they had no, a few, many, or very many moles. They observed that women with “very many” nevi had a 13% higher breast cancer risk than women reporting no nevi, although the association was no longer significant after adjusting for known breast cancer risk factors, especially benign breast disease or family history of breast cancer, which were themselves associated with nevi number.

These studies do not suggest that nevi cause breast cancer, but raise the possibility that nevi are affected by levels of sex hormones, which may be involved in the development of breast cancer. The findings do suggest that the number of nevi could be used as a marker of breast cancer risk, but it is unclear whether or how this information would improve risk estimation based on established risk factors. The accuracy of the findings is limited by the use of self-reported data on nevus numbers. Moreover, these findings may not apply to non-white women given that these studies involved mostly white participants.

In a linked Perspective, Barbara Fuhrman and Victor Cardenas discuss the potential implications of the findings from these studies. They say: “Additional studies should be carried out to investigate melanocytic nevi and other cutaneous features in association with the risks of breast cancer and other estrogen-related proliferative diseases. It is our hope that this research will provide etiologic insights and test practical uses of nevi and related phenotypes for their potential utility in breast cancer risk assessment.”

- MFP News Services
- 7-9-14