Comparison of immunohistochemical mesothelial biomarkers in paired biopsies and effusion cytology cell blocks from pleural mesothelioma.

Objective: Traditionally, the diagnosis of pleural mesothelioma is based on histological material. Minimally invasive effusion cytology specimens are an alternative that, like biopsies, require ancillary analyses. Validation of immunohistochemical (IHC) analyses on cytology, including the surrogate markers for molecular alterations BAP1 and MTAP, is of interest.

PD-L1 Expression in Non-Small Cell Lung Cancer Specimens: Association with Clinicopathological Factors and Molecular Alterations.

Immune checkpoint inhibitors (ICI) targeting programmed cell death-1 or its ligand (PD-L1) have improved outcomes in non-small cell lung cancer (NSCLC). High tumor PD-L1 expression, detected by immunohistochemistry (IHC) typically on formalin-fixed paraffin-embedded (FFPE) histological specimens, is linked to better response. Following our previous investigation on PD-L1 in cytological samples, the aim of this study was to further explore the potential impacts of various clinicopathological and molecular factors on PD-L1 expression.

Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer.

PD-L1 expression assessed by immunohistochemical staining is used for the selection of immunotherapy in non-small cell lung cancer (NSCLC). Appropriate validation of PD-L1 expression in cytology specimens is important as cytology is often the only diagnostic material in NSCLC. In a previous study comprising two different cohorts of paired biopsies and cytological specimens, we found a fairly good cyto-histological correlation of PD-L1 expression in one, whereas only a moderate correlation was found in the other cohort.

PD-L1 Testing in Cytological Non-Small Cell Lung Cancer Specimens: A Comparison with Biopsies and Review of the Literature.

Introduction: Programmed death-ligand 1 (PD-L1) expression is used for treatment prediction in non-small cell lung cancer (NSCLC). While cytology may be the only available material in the routine clinical setting, testing in clinical trials has mainly been based on biopsies.

Methods: We included 2 retrospective cohorts of paired, concurrently sampled, cytological specimens and biopsies.

Higher concordance of PD-L1 expression between biopsies and effusions in epithelioid than in nonepithelioid pleural mesothelioma.

Background: Malignant mesothelioma (MM) is a therapy-resistant tumor, often causing an effusion. Drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have shown promising results, but assessment of PD-L1 expression to select patients for therapy has mainly been performed on histologic tissue samples. In a previous study, we showed that MM effusions are suitable for PD-L1 assessment with results comparable to those reported in histologic studies, but no studies have compared PD-L1 expression in histologic and cytologic samples.

Immune effector monocyte-neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer.

Metastatic behavior varies significantly among breast cancers. Mechanisms explaining why the majority of breast cancer patients never develop metastatic outgrowth are largely lacking but could underlie the development of novel immunotherapeutic target molecules. Here we show interplay between nonmetastatic primary breast cancer and innate immune response, acting together to control metastatic progression.

Determination of PD-L1 expression in effusions from mesothelioma by immuno-cytochemical staining.

Background: Malignant mesothelioma (MM) is an aggressive, fatal tumor. Current therapeutic options only marginally improve survival. Programmed cell death ligand 1 (PD-L1) is a dominant mediator of immunosuppression, binding to programmed cell death 1 (PD-1).

Guidelines for cytopathologic diagnosis of epithelioid and mixed type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.

To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks.

Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.

Objective: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma.

Data Sources: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks.

Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.

Objective: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma.

Data Sources: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks.

Telomerase activity analyzed with TRAP in situ provides additional information in effusions remaining equivocal after immunocytochemistry and hyaluronan analysis.

Cytology is central in the diagnosis of malignancy in effusions. Ancillary techniques, mainly immunocytochemistry, have considerably improved the sensitivity but some 10% of all cases remain equivocal and require the addition of new diagnostic modalities. We have previously shown that strong nuclear telomerase activity determined with Telomere Repeat Amplification Protocol (TRAP) in situ is specific for malignant cells and could be a candidate for an additional test.

Liquid-based cytology using CytoRich Red/Tripath is diagnostically equivalent to conventional smears for bronchial washings and brushings and reduces the cost.

A split sample study was performed on 109 bronchial brushings and washings and evaluated from conventional slides (CS) and CytoRich Red/Tripath preparations (CRR/Tripath). Unassessable bronchial washings were significantly more frequent in CS (5 vs. 0), but as all brushings were assessable with both methods, no overall diagnostic advantage was found.

Preparation of DNA from cytological material: effects of fixation, staining, and mounting medium on DNA yield and quality.

Background: Personalized oncology requires molecular analysis of tumor cells. Several studies have demonstrated that cytological material is suitable for DNA analysis, but to the authors' knowledge there are no systematic studies comparing how the yield and quality of extracted DNA is affected by the various techniques used for the preparation of cytological material.

Methods: DNA yield and quality were compared using cultured human lung cancer cells subjected to different preparation techniques used in routine cytology, including fixation, mounting medium, and staining.

Possibility of mixed progenitor cells in sea star arm regeneration.

In contrast to most vertebrates, invertebrate deuterostome echinoderms, such as the sea star Asterias rubens, undergo regeneration of lost body parts. The current hypothesis suggests that differentiated cells are the main source for regenerating arm in sea stars, but there is little information regarding the origin and identity of these cells. Here, we show that several organs distant to the regenerating arm responded by proliferation, most significantly in the coelomic epithelium and larger cells of the pyloric caeca.

Podoplanin is a useful marker for identifying mesothelioma in malignant effusions.

The diagnosis of malignant mesothelioma in serosal effusions continues to be a major challenge because some of its cytomorphological features closely resemble adenocarcinomas. Immunohistochemistry is a valuable tool in the differentiation of epithelioid mesothelioma from metastatic adenocarcinomas. However, no single antibody has demonstrated absolute sensitivity or specificity.

Telomerase activity in effusions: a comparison between telomere repeat amplification protocol in situ and conventional telomere repeat amplification protocol assay.

Context: We previously found telomere repeat amplification protocol (TRAP) in situ helpful in the diagnosis of malignancy in effusions, whereas varying sensitivities and specificities for malignancy were reported by investigators using extract-based TRAP.

Objective: To compare the 2 methods and to elucidate the discrepancies between them.

Design: Twenty-three effusions were analyzed.

CK5/6 in effusions: no difference between mesothelioma and pulmonary and nonpulmonary adenocarcinoma.

Objective: To test the performance of CK5/6 for the differentiation between mesothelioma, adenocarcinoma and benign mesothelia/proliferations in effusion cytology.

Study Design: CKS/6 immunocytochemistry was applied to ethanol-fixed cytospin preparations from 74 benign and malignant effusions.

Results: Reactivity was seen in 7 of 8 mesotheliomas and in 9 of 11 benign mesothelial proliferations but also in 11 of l7 pulmonary adenocarcinomas and in 12 of 31 adenocarcinomas of nonpulmonary origin.

No detection of SV40 DNA in mesothelioma tissues from a high incidence area in Sweden.

Simian virus 40 (SV40), a polyoma virus of the rhesus macaque was discovered in 1960 as a contaminant of human polio vaccines produced in monkey cells. A number of studies have reported the detection of SV40 nucleotide sequences in human tumors, mainly mesotheliomas, but the reports have not been consistent. The presence of SV40 in 26 consecutive cases of malignant mesothelioma of biphasic type was investigated using a SV40 quantitative real time polymerase chain reaction (PCR) with a sensitivity of 10 copies of viral DNA per sample.

Comparison of NCL-hTERT antibody reactivity and telomere repeat amplification protocol in situ in effusions.

Objective: To compare the performances of 2 methods, telomerase repeat amplification protocol (TRAP) in situ and antibodies to the hTERT protein, in assessing telomerase activity.

Study Design: TRAP in situ and immunohistochemistry with a commercial antibody (NCL-hTERT) was performed on 54 body cavity effusions. The results were compared and correlated to diagnosis.

Lower proliferation rate in metastatic effusion mesothelial cells than in benign effusions.

Objective: To determine the proliferation rates of mesothelial cells in metastatic and benign effusions.

Study Design: Immunohistochemistry was performed on formalin-fixed pellets from 16 malignant and 9 benign clinical effusions. Dual staining with antibodies against Ki-67 (MIB-1) and desmin was applied to all effusions to differentiate between benign mesothelial cells and malignant cells, and the proportions of desmin+/Ki-67+ and desmin+/Ki-67- cells were calculated.

Napsin A (TA02) is a useful alternative to thyroid transcription factor-1 (TTF-1) for the identification of pulmonary adenocarcinoma cells in pleural effusions.

The purpose of this study was to test napsin A as a diagnostic marker of metastatic lung adenocarcinoma in pleural effusions, and to compare its performance with TTF-1. Napsin A and TTF-1 reactivities were determined immunohistochemically on formalin-fixed paraffin embedded cell blocks from 50 pleural effusion (5 mesotheliomas, 10 mesothelial proliferations, 12 pulmonary, and 23 nonpulmonary metastases). The results were evaluated separately, and correlated to the final diagnoses.

Weak telomerase activity in malignant cells in metastatic serous effusions: correlation to short survival time.

Objective: The purpose of this study was to evaluate whether the intensity of telomerase activity measured on the cellular level in effusions correlates to survival time in cases of metastatic spread to the serous cavities.

Study Design: Telomere repeat amplification protocol (TRAP) in situ was applied to 46 effusions containing metastatic cancer cells.

Results: Weak telomerase activity in tumor cells was seen in 7 cases, and moderate or strong activity in 39 cases.

The reactivity to CK5/6 antibody in tumor cells from non-small cell lung cancers shed into pleural effusions predicts survival.

Lung cancer, especially adenocarcinoma and large cell carcinoma, tends to spread to the pleural cavities. Once an effusion develops, the prognosis is generally dismal. Immunocytochemistry is frequently applied to effusions for diagnostic purposes, but the prognostic value of markers in malignant effusions have thus far attracted less attention.

Wnt-5a protein expression in primary dukes B colon cancers identifies a subgroup of patients with good prognosis.

Oncogenic Wnt/beta-catenin signaling occurs in a majority of colorectal cancers. In contrast, very little is known about the role of the nontransforming Wnt protein family member Wnt-5a in those tumors. In the most common of the three colon cancer stages, Dukes B or lymph node-negative, the outcome is the hardest to predict.