The role of the pathologist in the design and conducting of biomarker-driven clinical trials in cancer: position paper of the European Society of Pathology.

Clinical trials in oncology are important tools to identify and establish new effective drugs for cancer treatment. Since the development of the concept of precision oncology, a huge number of multi-centric biomarker-driven clinical trials have been performed and promoted by either academic institutions or pharmaceutical companies. In this scenario, the role of pathologists is essential in multiple aspects, with new challenges that should be addressed.

Invasive micropapillary carcinoma of the breast and invasive breast carcinoma of no special type: a comparison of claudin proteins' expression and its impact on survival.

Invasive micropapillary carcinoma of the breast is characterized by clusters of cells presenting with inverted polarity. Although the apico-basal polarity is a fundamental property of the epithelium, the biological alterations leading to the inside-out pattern observed in invasive micropapillary carcinoma (IMPC) remain mostly unknown. The regulation of tight junctions in polarity formation and maintenance is acknowledged.

Digital Whole Slide Image Analysis of Elevated Stromal Content and Extracellular Matrix Protein Expression Predicts Adverse Prognosis in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and limited treatment options. This study evaluates the prognostic value of stromal markers in TNBC, focusing on the tumor-stroma ratio (TSR) and overall stroma ratio (OSR) in whole slide images (WSI), as well as the expression of type-I collagen, type-III collagen, and fibrillin-1 on tissue microarrays (TMAs), using both visual assessment and digital image analysis (DIA). A total of 101 female TNBC patients, primarily treated with surgery between 2005 and 2016, were included.

Revisiting surgical margins for invasive breast cancer patients treated with breast conservation therapy - Evidence for adopting a 1 mm negative width.

Clinical trials have demonstrated conclusively the non-inferiority of breast-conserving surgery followed by breast radiation therapy (BCT) compared with mastectomy for the treatment of early-stage invasive breast cancer (BC). The definition of the required surgical margin to ensure adequate removal of the cancer by BCT to obtain an acceptable low local recurrence (LR) rate remains controversial. Meta-analyses published by Houssami et al.

TRPS1 expression in breast angiosarcoma.

Angiosarcoma (AS) of the breast, a rare mesenchymal neoplasm, exhibits distinct forms based on etiological and genetic features. While cases with typical clinical presentation and morphology allow for a straightforward diagnosis, challenges arise when clinical data are scarce, diagnostic material is limited, or morphological characteristics overlap with other tumors, including undifferentiated carcinomas. The trichorhinophalangeal syndrome protein 1 (TRPS1), once regarded as highly specific for breast carcinomas, now faces doubts regarding its reliability.

Dataset for reporting of the invasive carcinoma of the breast: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Background And Objectives: Current national or regional guidelines for the pathology reporting on invasive breast cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with invasive cancer of the breast. The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organizations.

Microsatellite instability and mismatch repair protein deficiency: equal predictive markers?

Current clinical guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) tests as predictive markers of immunotherapies. Most of the pathological guidelines consider MMR protein IHC as the gold standard test to identify cancers with MMR deficiency and recommend molecular MSI tests only in special circumstances or to screen for Lynch syndrome. However, there are data in the literature which suggest that the two test types may not be equal.

Research autopsy programmes in oncology: shared experience from 14 centres across the world.

While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research.

A dedicated structured data set for reporting of invasive carcinoma of the breast in the setting of neoadjuvant therapy: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Aims: The International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations, is an initiative aimed at providing a unified international approach to reporting cancer. ICCR recently published new data sets for the reporting of invasive breast carcinoma, surgically removed lymph nodes for breast tumours and ductal carcinoma in situ, variants of lobular carcinoma in situ and low-grade lesions. The data set in this paper addresses the neoadjuvant setting.

Comparison of standard mismatch repair deficiency and microsatellite instability tests in a large cancer series.

Background: The tumor-agnostic indication of immune checkpoint inhibitors to treat cancers with mismatch repair deficiency (dMMR)/microsatellite instability (MSI) increased the demand for such tests beyond Lynch syndrome. International guideline recommendations accept immunohistochemistry (IHC) for dMMR or molecular techniques (PCR or NGS) for MSI status determinations considering the two tests are equal, although there are scattered reports contradicting to this presumption.

Materials And Methods: Here we have directly compared four protein MMR immunohistochemistry (IHC) to MSI Pentaplex PCR test in a large cancer patient cohort (n = 1306) of our diagnostic center where the two tests have been run parallel in 703 cases.

Histopathological growth patterns and tumor-infiltrating lymphocytes in breast cancer liver metastases.

Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM.

The Prediction Analysis of Microarray 50 (PAM50) Gene Expression Classifier Utilized in Indeterminate-Risk Breast Cancer Patients in Hungary: A Consecutive 5-Year Experience.

Background: Breast cancer has been categorized into molecular subtypes using immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH) since the early 2000s. However, recent research suggests that gene expression testing, specifically Prosigna Prediction Analysis of Microarray 50 (PAM50), provides more accurate classification methods. In this retrospective study, we compared the results of IHC/FISH and PAM50 testing.

Evaluation of the routine use of E-cadherin immunohistochemistry in the typing of breast carcinomas: results of a randomized diagnostic study.

Aims: Invasive lobular carcinoma (ILC) has distinct morphology and association with loss of E-cadherin function. It has special clinical and imaging features, and its proper recognition is important. Following a recent proposal, we tested the value of the routine use of E-cadherin immunohistochemistry (IHC) in recognizing ILC.

Third International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB).

[Molecular epidemiology of microsatellite instability/mismatch repair deficiency in our institute - methodical aspects].

Molecular epidemiology of mismatch repair deficiency (dMMR)/microsatellite instability (MSI) are different in various ethnic groups; accordingly, our aim was to test this in a large single-center Hungarian cancer patient cohort. We have found that dMMR/MSI incidence correlates well with TCGA data in case of colorectal, gastric and endometrial cancers. We have also observed that immunohistochemistry- based dMMR incidences are higher as compared to MSI.

Genomic Landscape of Normal and Breast Cancer Tissues in a Hungarian Pilot Cohort.

A limited number of studies have focused on the mutational landscape of breast cancer in different ethnic populations within Europe and compared the data with other ethnic groups and databases. We performed whole-genome sequencing of 63 samples from 29 Hungarian breast cancer patients. We validated a subset of the identified variants at the DNA level using the Illumina TruSight Oncology (TSO) 500 assay.

Tumour-stroma ratio (TSR) in breast cancer: comparison of scoring core biopsies versus resection specimens.

Purpose: Tumour-stroma ratio (TSR) is an important prognostic and predictive factor in several tumour types. The aim of this study is to determine whether TSR evaluated in breast cancer core biopsies is representative of the whole tumour.

Method: Different TSR scoring methods, their reproducibility, and the association of TSR with clinicopathological characteristics were investigated in 178 breast carcinoma core biopsies and corresponding resection specimens.

ONEST (Observers Needed to Evaluate Subjective Tests) Analysis of Stromal Tumour-Infiltrating Lymphocytes (sTILs) in Breast Cancer and Its Limitations.

Tumour-infiltrating lymphocytes (TILs) reflect antitumour immunity. Their evaluation of histopathology specimens is influenced by several factors and is subject to issues of reproducibility. ONEST (Observers Needed to Evaluate Subjective Tests) helps in determining the number of observers that would be sufficient for the reliable estimation of inter-observer agreement of TIL categorisation.

Application of Sensors for Incorrect Behavior Identification in a Transport System.

This article focuses on cranes that are moving on a fixed crane track. There are specific problems and malfunctions arising during the operation of these cranes caused mainly by the crane skewing phenomenon. Crane skewing induces undesirable additional forces as a result of force contact between the crane wheel flange and the head of the crane track rail.

Addition of Chromosome 17 Polysomy and Amplification Status Improves the Accuracy of Clinicopathological Factor-Based Progression Risk Stratification and Tumor Grading of Non-Muscle-Invasive Bladder Cancer.

Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) significantly worsens life expectancy. Its risk can be assessed by clinicopathological factors according to international guidelines. However, additional molecular markers are needed to refine and improve the prediction.

Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer.

Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer (BC), accounting for up to 15% of all invasive BC. Loss of cell adhesion due to functional inactivation of E-cadherin is the hallmark of ILC. Although the current world health organization (WHO) classification for diagnosing ILC requires the recognition of the dispersed or linear non-cohesive growth pattern, it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC).

Pathological Diagnosis, Work-Up and Reporting of Breast Cancer 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.

Deconstructing Immune Cell Infiltration in Human Colorectal Cancer: A Systematic Spatiotemporal Evaluation.

Cancer-related immunity has been identified as playing a key role in the outcome of colorectal cancer (CRC); however, the exact mechanisms are only partially understood. In this study, we evaluated a total of 242 surgical specimen of CRC patients using tissue microarrays and immunohistochemistry to evaluate tumor infiltrating immune cells (CD3, CD4, CD8, CD20, CD23, CD45 and CD56) and immune checkpoint markers (CTLA-4, PD-L1, PD-1) in systematically selected tumor regions and their corresponding lymph nodes, as well as in liver metastases. Additionally, an immune panel gene expression assay was performed on 12 primary tumors and 12 consecutive liver metastases.