bims-mesote 2021-04-25 papers

Issue of 2021–04–25
five papers selected by
Laura Mannarino, Humanitas Research

Clin Lung Cancer. 2021 Mar 27. pii: S1525-7304(21)00065-6. [Epub ahead of print]

Three Decades of Malignant Pleural Mesothelioma: An Academic Center Experience.

Abdullah Nasser, Andrew Baird, Mathieu D Saint-Pierre, Kayvan Amjadi, Scott Laurie, Paul Wheatley-Price.

BACKGROUND: Malignant pleural mesothelioma (MPM) remains a challenging disease to manage. In the past few decades, extrapleural pneumonectomy (EPP), pemetrexed-based chemotherapy, and indwelling pleural catheters were introduced to MPM care with variable levels of efficacy and evidence.
PATIENTS AND METHODS: This was a retrospective review of patients diagnosed with MPM between January 1991 and March 2019. The primary outcome was overall survival (OS). Data were examined by decade to assess trends in MPM demographics, management, and OS. A subgroup analysis was then conducted to examine the impact of EPP, pemetrexed, and indwelling pleural catheters on OS.
RESULTS: The study included 337 patients; 309 patients had died at last follow-up (91.7%). Median age at diagnosis and the proportion of female patients increased from 65.8 years (interquartile range [IQR], 57.1-73.7) and 11.6% female from 1991 to 1999 to 75 years (IQR, 68.1-80.6) and 20.5% female from 2010 to 2019. Median OS was largely unchanged in the three study periods: 9.0 months (95% confidence interval [CI], 6.9-12.7) in the 1991-1999 cohort, 9.3 months (95% CI, 7.6-13.2) in the 2000-2009 cohort, and 10.1 months (95% CI, 7.9-13.6) in the 2010-2019 cohort. Controlling for a number of demographic and prognostic factors, EPP (hazard ratio [HR] = 0.50; 95% CI, 0.3-0.9; P = .02), pemetrexed-based chemotherapy (HR = 0.59; 95% CI, 0.40-0.87; P = .007), and indwelling pleural catheters (HR = 0.3; 95% CI, 0.13-0.71; P = .006) were each associated with improvements in OS.
CONCLUSION: Despite the small incremental improvements in survival shown by the three interventions we examined, prognosis remains guarded for MPM patients. Better modalities of management are needed.

Keywords: Catheters; Demographics; Pemetrexed; Pneumonectomy; Survival

DOI: https://doi.org/10.1016/j.cllc.2021.03.011

Mol Med Rep. 2021 Jun;pii: 467. [Epub ahead of print]23(6):

Transcriptomic alterations in malignant pleural mesothelioma cells in response to long‑term treatment with bullfrog sialic acid‑binding lectin.

Takeo Tatsuta, Arisu Nakasato, Shigeki Sugawara, Masahiro Hosono.

Malignant pleural mesothelioma (MPM) is a universally lethal type of cancer that is increasing in incidence worldwide; therefore, the development of new drugs for MPM is an urgent task. Bullfrog sialic acid‑binding lectin (cSBL) is a multifunctional protein that has carbohydrate‑binding and ribonuclease activities. cSBL exerts marked antitumor activity against numerous types of cancer cells, with low toxicity to normal cells. Although in vitro and in vivo studies revealed that cSBL was effective against MPM, the mechanism by which cSBL exerts antitumor effects is not fully understood. To further understand the mechanism of action of cSBL, the present study aimed to identify the key molecules whose expression was affected by cSBL. The present study established cSBL‑resistant MPM cells. Microarray analyses revealed that there were significant pleiotropic changes in the expression profiles of several genes, including multiple genes involved in metabolic pathways in cSBL‑resistant cells. Furthermore, the expression of some members of the aldo‑keto reductase family was revealed to be markedly downregulated in these cells. Among these, it was particularly interesting that cSBL action reduced the level of AKR1B10, which has been reported as a biomarker candidate for MPM prognosis. These findings revealed novel aspects of the effect of cSBL, which may contribute to the development of new therapeutic strategies for MPM.

DOI: https://doi.org/10.3892/mmr.2021.12106

Epidemiol Prev. 2021 Jan-Apr;45(1-2):45(1-2): 72-81

[BRIC-59 study: first results and considerations on the pathway on the access to health care for malignant pleural mesotheliomas].

Elisabetta Chellini, Martina Donzellini, Sara Ricciardi, Lucia Kundisova, Lucia Giovannetti, Francesca Battisti, Martina Giusti, Barbara Dallarti, Carolina Mensi.

OBJECTIVES: to define the most frequent health pathways of cases affected by malignant pleural mesothelioma according to those suggested and evaluated by the most recent specific guidelines.
DESIGN: epidemiological descriptive study.
SETTING AND PARTICIPANTS: 100 cases histologically or cytologically well defined during 2015-2017 are extracted from the archive of two Regional Mesothelioma Registries: in Tuscany Region (Central Italy) they are randomly extracted, while in Lombardy Region (Northern Italy) cases treated by a highly-specialized health centre are collected.
MAIN OUTCOME MEASURES: frequency of the diagnostic and therapeutic procedures; development and application of the checklist with evaluation of the duration of some phases of the predefined pathway.
RESULTS: all hospital medical records were collected only for 34 cases in Tuscany and 20 cases in Lombardy. The health examinations were supplied according to each case's health condition and it was not possible to define one or more structured and standardized pathways. The pre-diagnostic phase has a variable duration according to the initial health condition of the patient, also for his/her comorbidity, and to the hospital where he/she was hospitalized at first. The examinations in outpatient services (medical examinations, blood chemistry tests and radiological examinations) are several, but they are specially requested during the pre-diagnostic phase and during the period of chemotherapy. The checklist applied to a subset of Tuscan cases shows a large variation of the length of the pre-diagnostic phase (6-330 days), of the time interval between diagnosis and reporting to mesothelioma registry (1-200 days), and of the survival time (8 days - alive at 31.12.2019).
CONCLUSIONS: to obtain the best health pathways for malignant pleural mesotheliomas, it is necessary a strong network among the health regional services with a clinical multiprofessional coordination located in hospitals characterized by a long experience on these cases, and with an active regional monitoring on all clinical, psychological, epidemiological, and legal aspects of the pathway. The regional mesothelioma registries could give a high contribution thanks to their epidemiological skills which are necessary for the monitoring.

DOI: https://doi.org/10.19191/EP21.1-2.P072.041

Pediatr Dev Pathol. 2021 Apr 19. 10935266211008438

Metastatic Malignant Peritoneal Mesothelioma Mimicking an Autoinflammatory Syndrome in a 12-Year-Old Boy.

Gabriel Olmedilla, Clara Undaondo, Wenceslao Vasquez, Nuria Rodriguez.

A case of a malignant peritoneal mesothelioma mimicking an autoinflammatory syndrome in a 12-year-old boy is reported. The patient initially presented with lymphadenopathy and weight loss but without abdominal pain. Three things confounded the initial diagnosis: a positive test result for a gene related to cryopyrin-associated periodic syndrome, a positive response to the autoinflammatory syndrome treatment, and a lymph node biopsy which showed "hyperplastic mesothelial cells in the lymph sinuses." His symptoms relapsed several years later, and a peritoneal biopsy confirmed the final diagnosis. Complete morphological, immunohistochemical, and molecular diagnoses are described. A translocation in the TERT gene involving the truncation of the promoter was found in the mesothelioma. The translocation has never been described in mesotheliomas and is of an unknown significance.

Keywords: TERT promoter translocation; autoinflammatory syndrome; epithelioid; malignant mesothelioma; pediatric; peritoneum

DOI: https://doi.org/10.1177/10935266211008438

J Mol Diagn. 2021 Apr 19. pii: S1525-1578(21)00090-8. [Epub ahead of print]

DNA methylation profiling discriminates between malignant pleural mesothelioma and neoplastic or reactive histological mimics.

Luca Bertero, Luisella Righi, Giammarco Collemi, Christian Koelsche, Yanghao Hou, Damian Stichel, Daniel Schrimpf, Uta Flucke, Iver Petersen, Christian Vokuhl, Stefan Fröhling, Paolo Bironzo, Giorgio Vittorio Scagliotti, Paola Cassoni, Mauro Papotti, Andreas von Deimling.

Diagnosis of malignant pleural mesothelioma (MPM) is a challenging task because of its potential overlap with other neoplasms or even with reactive conditions. Recently, DNA methylation analysis proved to be an effective tool for tumor diagnosis. In the present study, this approach was tested for MPM diagnosis. A discovery (n=33) and an independent validation cohort (n=46) of MPM samples were subjected to array-based DNA methylation analyses and their DNA methylation patterns were compared to those of 202 cases representing malignant and benign diagnostic mimics. These comprised solitary fibrous tumor (n=20), synovial sarcoma (n=30), leiomyosarcoma (n=20), angiosarcoma (n=20), nodular fasciitis (n=10), desmoid-type fibromatosis (n=10), epithelioid sarcoma (n=20), lung adenocarcinoma (n=15), lung squamous cell carcinoma (n=15), melanoma (n=20), reactive mesothelial hyperplasia (n=12) and sclerosing fibrous pleuritis (n=10). Copy number variations (CNV) profiles were also inferred. By both unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analysis, MPM samples of the discovery cohort exhibited a distinct DNA methylation profile, different from that of other neoplastic and reactive mimics. These results were confirmed in the independent validation cohort and by in silico analysis of the MPM TCGA dataset. CNV profiles enabled to identify MPM molecular hallmarks including CDKN2A and NF2 deletions. Methylation profiling proved to be an effective tool for the MPM diagnostics, although caution is advised in samples with low tumor cell content.

DOI: https://doi.org/10.1016/j.jmoldx.2021.04.002