Factors In Malignant Pleural Mesothelioma Research Articles

P2.21-01 Inflammatory Biomarkers as Prognostic Factors for Malignant Pleural Mesothelioma

P2.21-01 Inflammatory Biomarkers as Prognostic Factors for Malignant Pleural Mesothelioma

Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma.

To determine the mechanism of EPE in downregulating TYMS in MPM cancer. The TYMS mRNA expression with epithelial-to-mesenchymal transition biomarkers and nuclear factor SP1 was assessed using the GEO database in a data set of MPM patients (GSE51024). Invasive MPM cell lines were in vitro models for the investigation of TYMS expression after EPE treatment. The tyms promoter SP1 binding sequences were determined using Genomatix v 3.4 software Electrophoretic mobility shift and dual-luciferase reporter assays revealed specific SP1 motifs in the interaction of EPE and reference compounds. Chromatin immunoprecipitation and Re-ChIP were used for the co-occupancy study. In MPM patients, a positive correlation of overexpressed TYMS with mesenchymal TWIST1, FN1 and N-cadherin was observed. EPE and its major components, gallic and ellagic acid (GA and EA, respectively), downregulated TYMS in invasive MPM cells by interacting with particular SP1 motifs on the tyms promoter. The luciferase constructs confirmed the occupation of two SP1 regulatory regions critical for the promotion of TYMS expression. Both EPE and reference standards influenced SP1 translocation into the nucleus. EPE components reduced TYMS expression by occupation of SP1 motifs on the tyms promoter and reversed the EMT phenotype of invasive MPM cells. Further in-depth analysis of the molecular docking of polyphenol compounds with SP1 regulatory motifs is required.

Pleural Fluid-to-Blood BNP Ratio May Contribute to Prognosis in Malignant Pleural Mesothelioma.

Brain natriuretic peptide (BNP) seems to be produced from malignant mesothelial cells other than cardiomyocytes. We aimed to evaluate whether an increased pleural fluid-to-blood BNP ratio in patients with malignant pleural mesothelioma (MPM) could facilitate prognosis beyond diagnosis. Patients with MPM were included (observational study). One- and two-year survival and factors affecting it were tested. To evaluate the prognostic significance of the natriuretic peptide precursor B (NPPB) gene expression in MPM, we constructed a survival curve from data derived from The Cancer Genome Atlas. Nineteen consecutive patients with MPM were included (age: 67 (61, 80), male 78.9%). One- and two-year survival were 52.6% and 31.6%, respectively. Age, performance status, and the other variables tested did not differ between survivors and non-survivors. Non-survivors presented higher pleural fluid BNP in two years (699 (210, 5000) vs. 379.5 (5, 567), p = 0.036) and BNP ratios than survivors (1-year: 28.75 (4.05, 150.24) vs. 3.49 (0.3, 26) p = 0.001, 2-years: 22.8 (2.42, 150.24) vs. 3.49 (0.3, 7.76), p = 0.001). One- and two-year survival rates in patients with BNP ratios above/equal to the median value (8.82) were 20% and 0%, and 88.9% and 66.7%, respectively, in patients with BNP ratios below 8.82 (p = 0.006 and p = 0.002, respectively). MPM patients with low NPPB expression presented significantly higher survival rates compared to patients with higher expressions (p = 0.032). A high pleural fluid/blood BNP ratio, an easily performed in everyday practice, costless biomarker seems to predict poorer survival better than the commonly reported prognostic factors in MPM.

Prognostic risk assessment model for alternative splicing events and splicing factors in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and highly malignant thoracic tumor. Although alternative splicing (AS) is associated with tumor prognosis, the prognostic significance of AS in MPM is unknown. Transcriptomic data, clinical information, and splicing percentage values for MPM were obtained from The Cancer Genome Atlas (TCGA) and TCGA SpliceSeq databases. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analyses were performed to establish a model affecting the prognosis of MPM. Survival and ROC analyses were used to test the effects of the prognostic model. LASSO/multivariate Cox analysis was used to construct the MPM prognostic splicing factor (SF) model. The SF-AS interaction network was analyzed using Spearman correlation and visualized using Cytoscape. The association between the MPM prognostic SF model and drug sensitivity to chemotherapeutic agents such as cisplatin was analyzed using pRRophetic.R. The LASSO/multivariate Cox analysis identified 41 AS events and 2 SFs that were mostly associated with survival. Nine prognostic prediction models (i.e., seven types of AS model, total AS model, and SF model) were developed. An MPM prognostic SF-AS regulatory network was subsequently constructed with decreased drug sensitivity in the SF model high-risk group (p=0.025). This study provides the first comprehensive analysis of the prognostic value of AS events and SFs in MPM. The SF-AS regulatory network established in this study and our drug sensitivity analysis using the SF model may provide novel targets for pharmacological studies of MPM.

A multicentric analysis of prognostic factors in malignant pleural mesothelioma

Background: Malignant pleural mesothelioma is a rare entity with poor prognosis, linked to previous asbestos exposure. The main goal of this study was to analyse the impact of clinical factors on mesothelioma prognosis. Methods: Retrospective cohort study of patients with malignant pleural mesothelioma in three Portuguese institutions, from 1999 to 2020. Statistical analysis was performed with Kaplan–Meier method and Cox regression using IBM SPSS® v25. Results: 60 patients were included, with male predominance (70%) and a median age of 69 years old. At diagnosis, 61% had advanced TNM stage (TNM III-IV) and 18% had an ECOG-PS ≥ 2. Asbestos exposure was stated in 48%. Epithelioid mesothelioma was the most prevalent histological subtype (81%). The majority received first line chemotherapy, in 10% combined with surgery, and two patients received immunotherapy after progression. Median overall survival (OS) was 13 months and median progression free survival was 10 months. A lower OS was observed in patients with ECOG-PS ≥ 2, age ≥ 70 years, TNM stage III-IV, anaemia, and hypoalbuminemia. Applying the decision tree model proposed by Brims et al. in our population, a significant difference in median OS was observed between the risk groups. In a multivariate analysis using Cox regression, Brims risk group 4, older age and advanced TNM stage were identified as independent negative prognostic factors. Conclusion: Recognition of these prognostic factors at diagnosis and use of specific prognostic models can help guide malignant pleural mesothelioma management.

Bioinformatic Analysis of Potential Biomarker for hsa-miR-196b-5p in Mesothelioma.

Purpose: Malignant pleural mesothelioma is a rare neoplasia with a poor prognosis, and the majority of patients have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Materials and Methods: To determine the cytotoxicity of geldanamycin in mesothelioma H28 cells, the MTT assay was used. To determine changes in microRNA (miRNA) expression in geldanamycin-treated H28 cells, miRNA microarray analysis was performed. To determine the function of miR-196b-5p, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of miR-196b-5p targets predicted by miRwalk. Results: Our data showed that geldanamycin treatment reduced H28 cell viability in a dose-dependent manner. MicroRNA array analyses showed that expression of hsa-miR-196b-5p was downregulated in geldanamycin-treated H28 cells. Geldanamycin regulated miRNAs with roles in processes such as aging, angiogenesis, apoptosis, cell cycle, cell differentiation, cell proliferation, DNA repair, and secretion. Survival analysis showed that decreased expression of hsa-miR-196b-5p was significantly associated with a better outcome in mesothelioma patients. Expression of miR-196b-5p was also significantly associated with the developmental stages of mesothelioma. To narrow down the target genes of miR-196b-5p, we determined the overlap between the predicted target genes of miR-196b-5p and downregulated mRNAs in ovarian cancer based on the Gene Expression Omnibus dataset GSE12345. PDE1A, LAMA4, and PAPPA were identified as both miR-196b-5p targets and downregulated genes in GSE12345 and were thus considered targets of miR-196b-5p. Gene-miRNA expression correlation analysis showed that PDE1A, LAMA4, and PAPPA expression was negatively correlated with miR-196b-5p expression. Conclusions: We suggest that geldanamycin has potential for the treatment of mesothelioma via regulating miR-196b-5p. Furthermore, miR-196b-5p may be a potential biomarker for mesothelioma.

Survival of Korean Patients with Malignant Pleural Mesothelioma Compensated for the Asbestos Injury Relief

Background: The purpose of this study was to identify the epidemiologic characteristics and prognostic factors for malignant pleural mesothelioma in Korea, which are currently insufficient. The data were derived from malignant mesothelioma patients who registered under the Asbestos Injury Relief Act; Methods: A total of 728 patients received compensation from the Asbestos Injury Relief Act due to malignant mesothelioma between 2011 and 2015. Of these, 313 patients (43.0%) with malignant pleural mesothelioma were included in the study. The study variables were sex (male, female), age at diagnosis (<59, 60–69, ≥70), smoking history (yes, no), surgery (yes, no), chemotherapy (yes, no), occupational exposure to asbestos (yes, no), and histological subtype (epithelioid, nonepithelioid); Results: Median survival of mesothelioma was 8.0 months (95% confidence interval: 6.2 to 9.8). The 1-year, 2-year, and 5-year survival rates (%) were 43.5%, 23.6%, and 12.5%, respectively. In multivariate analysis of Cox’s proportional hazards model; sex, age, smoking history, occupational asbestos exposure, and histological subtype were not significant prognostic factors, but surgery and chemotherapy combined was a significant predictor; Conclusions: Although the representativeness of these data is limited, our study estimates the epidemiologic characteristics of malignant pleural mesothelioma. Non-occupational exposure had a similar prognosis to occupational asbestos exposure, and there was no sex difference. In addition, it was found that receiving a combination of surgery and chemotherapy affects the survival rate, but there is a limitation in that factors such as performance status, comorbidities, and stage that contribute to survival are not considered.

Prognostic factors for progression-free and overall survival in malignant pleural mesothelioma.

BackgroundMalignant pleural mesothelioma is an infrequent neoplasia with a poor prognosis and the majority of patients already have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years.MethodsThis was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, which compared histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact in the prognosis of overall survival (OS) and progression‐free survival (PFS).ResultsA total of 136 patients were included in the study. In the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). Median PFS was nine months (95% confidence interval [CI]: 8.4–9.5 months) and median OS was 12 months (95% CI: 11.3–12.6). The results indicated that the most determining prognostic factors for OS and PFS were cell differentiation measured by immunohistochemical biomarkers, the treatment chosen, and that RECIST was the most significant in the evaluation of patient response to treatment.ConclusionsMalignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. Our study revealed that the prognostic factors for OS and PS were cell differentiation, the treatment chosen and RECIST.

Impact of Detecting Occult Pathologic Nodal Disease During Resection for Malignant Pleural Mesothelioma

BackgroundLymph node (LN) involvement is a poor prognostic factor for malignant pleural mesothelioma (MPM). However, to our knowledge, postresection outcomes of node-negative (cN0/pN0), occult pathologic nodal disease (cN0/pN+), and clinical node-positive disease (cN+) have not been compared to date. Patients and MethodsThe National Cancer Data Base was queried for newly diagnosed, resected MPM with known clinical/pathologic LN information. Three cohorts were compared: cN0/pN0, cN+, and cN0/pN+. Multivariable logistic regression examined predictors of pathologic nodal upstaging. Kaplan-Meier analysis with propensity matching assessed overall survival (OS); multivariate Cox proportional hazards modeling examined predictors thereof. ResultsOf 1369 patients, 687 (50%) had cN0/pN0, 457 (33%) cN+, and 225 (16%) cN0/pN+ disease. Median follow-up was 29 months. In patients with cN0 disease, factors associated with pathologic nodal upstaging were younger age, greater number of examined LNs, and nonsarcomatoid histology (P < .05 for all). Relative to pN0 cases, occult LN involvement (65% being pN2) was associated with 51% higher hazard of mortality on multivariate analysis (P = .005). Following propensity matching, the OS of cN0/pN+ was similar to cN+ cases (P = .281). On multivariate analysis, the number of involved LNs (continuous variable, P = .013), but not nodal tumor, node, metastasis (TNM) classification or LN ratio (P > .05 for both), was associated with OS. ConclusionDetecting occult nodal disease during resection for cN0 MPM is associated with poorer prognosis, with similar survival as cN+ cases, underscoring the importance of routine preoperative pathologic nodal assessment for potentially resectable MPM. The number of involved LNs (rather than current location-based classification) may provide more robust prognostic stratification for future TNM staging.

The Prognostic Role of TNM Staging Compared With Tumor Volume and Number of Pleural Sites in Malignant Pleural Mesothelioma

BackgroundAge, sex, stage, histotype, and surgery are the most recognized prognostic factors for malignant pleural mesothelioma (MPM). Tumor volume (TV) was suggested as an alternative prognostic evaluation. We aimed to assess the prognostic role of Tumor, Node, Metastases (TNM) versus TV and number of pleural sites (NPS). Patients and MethodsInformation on stage, TV, and NPS was collected for 52 MPM patients (pts) at our institution from 2009 to 2012. Baseline computed tomography imaging was performed to define TNM, TV, and NPS. Pts were divided in 3 stage groups: early (I-II), III, and IV. A dedicated computer system calculated TV. Pts were divided in 2 groups according to mean baseline TV (483 cm3). NPS was defined on the basis of the NPS macroscopically involved by disease (1-3). The association between TNM, tumor size (T), TV, NPS, TV and NPS, and overall survival was assessed using Cox models adjusted for age, sex, histology, and treatment. ResultsMost pts were male; mean age was 62 years. We showed an association between TV, TNM, and T. Stage III (hazard ratio [HR], 4.71; P = .02) and IV (HR, 7.40; P < .01), T3 (HR, 5.07; P < .01) and T4 (HR, 5.09; P < .01), TV > 483 cm3 (HR, 3.47; P < .01) and NPS 2 (HR, 3.00; P = .08) and 3 (HR, 6.05; P < .01) were predictive of worse survival. However, the TV and NPS combination performed better than TV, NPS, and TNM alone as a prognostic classifier. ConclusionWe showed that TV is related to TNM staging and T, in particular. Improved prognostic performance might be achievable using quantitative clinical staging combining TV and NPS.

Yield of pleural fluid cytology in those with risk factors for malignant pleural mesothelioma

Yield of pleural fluid cytology in those with risk factors for malignant pleural mesothelioma

The Role of Micronucleus Assay to Detect Genetic Instability in Respiratory Cancer Patients.

Asbestos represents the main risk factor for malignant pleural mesothelioma (PM) even if only a minority of exposed people develop this tumor, suggesting a significant role for genetic susceptibility. This study aims to evaluate micronuclei (MN) frequency as a biomarker of genome instability in peripheral blood lymphocytes of PM and lung cancer (LC) patients when compared with healthy controls (HCs) and patients with nonneoplastic respiratory diseases (RDs). Lymphocyte cytokinesis-block MN assay was carried out on 317 subjects. Mutagen sensitivity, measured by quantifying MN frequency after an in vitro challenge with ionizing radiation, was evaluated in 252 subjects. A significant increase in MN frequency was observed in cancer patients compared to HCs, with a mean ratio (MR) of 1.35 and 1.36 at baseline and 1.43 and 1.38 after irradiation in PM and LC patients, respectively. A positive (synergistic) interaction between asbestos exposure and disease status was observed for MN frequency after irradiation in PM patients with possible exposure to asbestos (MR = 1.62). The evidence of increased genetic damage in cancer cases confirms lymphocyte cytokinesis-block MN assay as a sensitive predictor of the role of genetic instability in carcinogenic processes.

Pleural thickness after neoadjuvant chemotherapy is a prognostic factor in malignant pleural mesothelioma

ObjectivesDefinitive diagnosis of the T-component is sometimes challenging in malignant pleural mesothelioma (MPM). Pleural thickness has been reported to be a prognostic factor for MPM and is a potential T-component. MethodsWe conducted a historical cohort study of patients who underwent neoadjuvant chemotherapy (NAC) and curative-intent surgery as a multimodal treatment for MPM from January 2007 to June 2016. The maximum measurement of pleural thickness among 3 levels and the sum at each level determined using axial computed tomography imaging before and after NAC were termed as “max” and “sum,” respectively. We assessed the association between pleural thickness and the primary and secondary end points of overall survival and recurrence-free survival. Survival was analyzed using the Kaplan–Meier curve, log rank test, and multivariate Cox regression model. ResultsWe enrolled 105 patients. We excluded 1 because of missing data; thus, the sample size was 104. The median follow-up period was 29.1 months with recurrence in 78 patients (70.3%) and death in 67 (60.4%). Max and sum ranged from pre (before NAC) values of 0 to 35 (median, 6.05) and 0 to 97 (median, 12.9) to post (after NAC) values of 0 to 30.8 (median, 4.25) and 0 to 67.0 (median, 9.25), respectively. Post values max and sum were associated with overall survival and recurrence-free survival. Post sum values were associated with recurrence (adjusted hazard ratio, 2.59; 95% confidence interval, 1.42-3.83) and death (adjusted hazard ratio, 2.13; 95% confidence interval, 1.16-4.52), respectively. ConclusionsPleural thickness after NAC was an independent prognostic factor in patients who underwent multimodal treatment.

Prognostic factors affecting survival in malignant pleural mesothelioma: analysis of 125 subjects

Determining the pre-treatment prognostic factors in malignant pleural mesothelioma is important in terms of estimating the course of the disease and selecting patients who are candidate for multimodal therapy. The aim of the study was to determine the prognostic factors affecting survival in patients with malignant pleural mesothelioma. One hundred and twenty-five patients who had been diagnosed histologically as having malignant pleural mesothelioma over the past 5 years were evaluated retrospectively. Relationships of survival of the patients with their age, gender, exposure to asbestos, smoking history, platelet, hemoglobin, leukocyte (WBC) and serum LDH values, histology, performance score and stage of disease were examined. Advanced clinical stage, N2 nodal involvement and the presence of distant metastasis were found to be related to survival. Sarcomatous histology was found to be a poor prognostic factor independently of other factors. We showed that histological subtype and stage of disease were the most important parameters in planning the treatment, especially in determining the patients who were candidate for multimodal treatment and in estimating the prognosis.

No implication of Simian virus 40 in pathogenesis of malignant pleural mesothelioma in Slovenia.

Malignant mesothelioma is predominantly caused by asbestos exposure, although the association of Simian virus 40 in its pathogenesis is currently still under debate. Simian virus 40, a DNA rhesus monkey virus with oncogenic properties, accidentally contaminated early batches of polio vaccine in the 1960s. In the 1990s, viral sequences and proteins were discovered in several human tumors, which triggered research to find a link between Simian virus 40 and human cancers, especially malignant mesothelioma. The aim of our study was to establish an effective laboratory procedure for Simian virus 40 detection and to investigate the presence of Simian virus 40 DNA and small t antigen in mesothelioma samples from Slovenian patients. Paraffin-embedded malignant pleural mesothelioma specimens from 103 Slovenian patients were collected and used for total DNA isolation and real-time polymerase chain reaction for Simian virus 40 small t and large T DNA analysis. Special attention was devoted to primer design, good laboratory practice and polymerase chain reaction contamination prevention. Polymerase chain reaction products were sequenced and BLAST aligned. One 5 microm thick paraffin section from each patient's tissue block was stained with hematoxylin and eosin for histological typing and one for immunohistochemical detection of Simian virus 40 small t antigen using a monoclonal antibody against Simian virus 40 (Pab280). SV40-expressing Wi-38 cells were used as positive control in both PCR and immunohistochemistry. In real-time polymerase chain reaction analyses, only 4 samples gave products with primer pairs amplifying small t antigen and were inconsistent and poorly reproducible. BLAST alignment showed no homology with any deposited SV40 sequences. No immunopositive staining for SV40 small t antigen was found in any of the samples. We found no evidence of SV40 presence in tissue samples from 103 Slovenian patients with malignant pleural mesothelioma. Asbestos exposure remains the main risk factor for malignant pleural mesothelioma in Slovenia.

PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma.

There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome. Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as>1% membranous staining regardless of intensity. Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR=2.02; 95% CI, 1.005-4.057; P-value=0.0484). Our analysis found a higher percentage of MPM patients with positive PD-L1 (>1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time.

P2.09-004 PD-L1 Protein Expression Is Negative Prognostic Factor in Malignant Pleural Mesothelioma in Central Europe

P2.09-004 PD-L1 Protein Expression Is Negative Prognostic Factor in Malignant Pleural Mesothelioma in Central Europe

LEUKOCYTOSIS AS A SIGNIFICANT POOR PROGNOSTIC FACTOR IN MALIGNANT PLEURAL MESOTHELIOMA PRODUCING GRANULOCYTE‐COLONY STIMULATING FACTOR: TWO CASE REPORTS AND LITERATURE REVIEW

RespirologyVolume 22, Issue S3 p. 192-192 APSR Poster Abstracts LEUKOCYTOSIS AS A SIGNIFICANT POOR PROGNOSTIC FACTOR IN MALIGNANT PLEURAL MESOTHELIOMA PRODUCING GRANULOCYTE-COLONY STIMULATING FACTOR: TWO CASE REPORTS AND LITERATURE REVIEW First published: 23 November 2017 https://doi.org/10.1111/resp.13207_271Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 192-192 RelatedInformation

P1.09-009 Evaluation of a Combined MicroRNA-Clinical Score as Prognostic Factor for Malignant Pleural Mesothelioma

P1.09-009 Evaluation of a Combined MicroRNA-Clinical Score as Prognostic Factor for Malignant Pleural Mesothelioma

Reproducibility for histologic parameters in peritoneal mesothelioma

Histologic subtype is recognized as a prognostic factor in malignant pleural mesothelioma. Specifically, epithelial morphology is associated with a better prognosis than other subtypes, and the same association is observed in peritoneal malignant mesothelioma. Recently, prognostic differences based on morphologic subtypes of epithelial peritoneal malignant mesothelioma were reported. Herein, we report the interobserver variability across four pathologists at three institutions. The authors independently reviewed 67 cases of malignant peritoneal epithelioid mesotheliomas and subclassified them according to their epithelial subtype: papillary, tubulopapillary, trabecular, micropapillary, solid and/or pleomorphic. The cases were also evaluated by each author for several other histopathologic parameters including depth of invasion, nuclear grade, lymphocytic host response, mitotic count/index, presence of lymphovascular invasion, and stromal desmoplasia. The interobserver agreement for histopathologic parameters was highest for mitotic rate (κ=0.36) and primary epithelial subtype (κ=0.32). The interobserver variability for solid subtype pattern was moderate (κ=0.49). We found that the interobserver variability for most histopathologic parameters is poor.