Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival

Paajanen, Juuso; Laaksonen, Sanna; Kettunen, Eeva; Ilonen, Ilkka; Vehmas, Tapio; Salo, Jarmo A.; Räsänen, Jari; Sutinen, Eva; Ollila, Hely; Mäyränpää, Mikko I.; Myllärniemi, Marjukka; Wolff, Henrik

doi:10.1016/j.humpath.2020.02.007

Cited by 12 publications

(17 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study sample consisted of 74 patients from a Finnish national MPM population diagnosed during 2000–2012 [ 1 ]. From the national MPM tissue sample cohort, subgroups of long‐term MPM survivors (LTS, survival >60 months) [ 2 , 17 ], epithelioid MPM patients (EMPM, median survival 14 months) [ 2 , 17 ], extended pleurectomy MPM patients (PD), and biphasic MPM patients (BMPM) with histological samples in the Helsinki Biobank were included for constructing tissue microarrays (TMAs). The TMAs were constructed in collaboration with the Helsinki Biobank.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma

Ollila

Paajanen

Wolff

et al. 2021

The Journal of Pathology CR

Self Cite

View full text Add to dashboard Cite

Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location‐specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all‐cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet‐derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p < 0.001). A multivariable survival analysis adjusted for clinical parameters and stromal mfIHC markers revealed that tumor cell PDGFRB and stromal SPARC remained independently associated with survival (HR = 1.01, 95% confidence interval [CI] = 1.00–1.03 and HR = 1.05, 95% CI = 1.00–1.11, respectively). The prognostic effect of PDGFRB was validated with an artificial intelligence‐based analysis method and further externally validated in another cohort of 117 MPM patients. In external validation, high tumor cell PDGFRB expression associated with shorter survival, especially in the epithelioid subtype. Our findings suggest PDGFRB and SPARC as potential markers for risk stratification and as targets for therapy.

show abstract

Section: Methodsmentioning

confidence: 99%

“…The main cause of MPM is exposure to asbestos and curative treatment is usually limited. Factors associated with long‐term survival (>60 months) in MPM patients remain unidentified [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma

Ollila

Paajanen

Wolff

et al. 2021

The Journal of Pathology CR

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the AB1 and AC29 there was indeed a deletion in the murine homologous region; however in cell line AB22 this region was duplicated (Additional file 1). For other tumor suppressor genes BAP1, NF2 and TP53 thought to play important roles in human MMs [10][11][12][13][14][15][16], there is even less or no concordance in the copy number variant regions of the three cell lines (Additional file 1).…”

Section: Discussionmentioning

confidence: 99%

“…These include numerical and structural chromosomal aberrations and molecular genetically detectable alterations in the cellular signal transduction pathways, among others caused by activation of oncogenes or loss of tumor suppressor genes [5]. In human the genes cyclin-dependent kinase inhibitor 2A (CDKN2A), neurofibromatosis type 2 (NF2), the breast cancer associated gene 1 (BRCA1) associated protein 1 (BAP1) and tumorsuppressorprotein 53 (TP53) genes seem to be major players in MM-pathogenesis and -progression [7][8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Histomorphologically and according to their growth parameters, MM can be divided into the following, most frequently observed subtypes: (1) biphasic, (2) epithelioid and (3) sarcomatoid. Different median survival times were attributed to each subtype; the best prognosis has the epithelioid, while the worst one has the sarcomatoid subtype [13,17].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cytogenomic characterization of three murine malignant mesothelioma tumor cell lines

et al. 2020

View full text Add to dashboard Cite

Background Malignant mesothelioma (MM) is a rare aggressive cancer primary located in pleura and lung. MMs can be divided into biphasic, epithelioid and sarcomatoid subtypes. In majority of cases MMs are induced by asbestos fiber exposure. As latency period after asbestos exposure ranges between ~ 10 and 60 years MMs are mainly observed in elder people. Human MM, being a rare tumor type, lacks detailed cytogenetic data, while molecular genetic studies have been undertaken more frequently. However, murine MM cell lines are also regularly applied to get more insight into MM biology and to test new therapy strategies. Results Here the murine MM cell lines AB1, AB22 and AC29 were studied by molecular cytogenetics and molecular karyotyping. Interestingly, yet there were no genetic or genomic studies undertaken for these already in 1992 established cell lines. The obtained data on genomic imbalances in these murine cell lines was translated into the human genome as previously reported based on human and murine genomic browsers. Conclusions It turned out that all three cell lines showed high similarities in copy number variants as observed typically in human MM. Also, all three cell lines were most similar to human epithelioid MMs, and should be used as models therefore.

show abstract

Reliability of assessing morphologic features with prognostic significance in cytology specimens of epithelioid diffuse pleural mesothelioma and implications for cytopathology reporting

Salama

Baine

et al. 2023

Cancer Cytopathology

View full text Add to dashboard Cite

Background The World Health Organization incorporates morphologic features with prognostic significance in the 2021 classification of epithelioid diffuse pleural mesothelioma (E‐DPM). Although cytology specimens are often the first and occasionally the only specimen available for patients with DPM, these features have not yet been investigated in cytology. Methods Nuclear atypia, pleomorphic features, necrosis, and architectural patterns were retrospectively assessed in 35 paired cytology and concurrent/consecutive surgical pathology specimens of E‐DPM. Agreement between pairs was determined via unweighted κ scores. Discordant cases were re‐reviewed to determine the reasons for disagreement. Results Interpretation of nuclear atypia in cytology was concordant with histology in all cases (κ = 1.000; p < .001). The presence of pleomorphic features and necrosis was concordant in 97.1% (κ = 0.842; p < .001) and 85.7% (κ = 0.481; p = .001) of paired cases, respectively. Assessment of architectural patterns in cytology showed only slight agreement with histology (κ = 0.127; p = .037). In cytology cases (n = 23) with cell block material available, assessment of nuclear atypia and the presence of pleomorphic features showed perfect agreement (κ = 1.000; p < .001, each), the presence of necrosis showed moderate agreement (κ = 0.465; p = .008), and assessment of architectural patterns showed slight agreement (κ = 0.162; p = .15) in paired specimens. Most disagreements were due to sampling differences between cytology and histology specimens. Conclusions Although complete nuclear grading of E‐DPM is not possible given the unreliability of mitotic counts in cytology, assessment of nuclear atypia in cytology specimens is shown to be reliable. Identification of pleomorphic features and necrosis is also reliable despite occasional sampling issues. Assessment of architectural patterns is more limited in cytology.

show abstract

Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival

Cited by 12 publications

References 30 publications

High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma

High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma

Cytogenomic characterization of three murine malignant mesothelioma tumor cell lines

Reliability of assessing morphologic features with prognostic significance in cytology specimens of epithelioid diffuse pleural mesothelioma and implications for cytopathology reporting

Contact Info

Product

Resources

About