How to Set Up a Molecular Pathology Lab: A Guide for Pathologists.

In today's pathology practice, pathologists combine molecular tests with conventional histopathological methods. Pathology laboratories should therefore be designed and operated in accordance with the requirements of molecular testing procedures. While the specifics of the requirements may vary depending on the spectrum of the tests that will be performed, there are several basic criteria that need to be fulfilled for standardization. Adequate space, appropriate equipment and qualified personnel are required to establish a molecular pathology laboratory. One of the most important points that should be taken into consideration while designing a molecular pathology laboratory is to create a plan to prevent contamination. As molecular diagnosis has a major role in treatment decisions, the management of the molecular pathology laboratory is of utmost importance. In this review, the criteria required to establish an optimal molecular pathology laboratory will be reviewed.

Responding to the Challenges of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Perspectives from the Association for Molecular Pathology Infectious Disease Subdivision Leadership.

Clinical molecular laboratory professionals are at the frontline of the response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing accurate, high-quality laboratory results to aid in diagnosis, treatment, and epidemiology. In this role, we have encountered numerous regulatory, reimbursement, supply-chain, logistical, and systems challenges that we have struggled to overcome to fulfill our calling to provide patient care. In this Perspective from the Association for Molecular Pathology Infectious Disease Subdivision Leadership team, we review how our members have risen to these challenges, provide recommendations for managing the current pandemic, and outline the steps we can take as a community to better prepare for future pandemics.

The Surveillance, Epidemiology, and End Results (SEER) Program and Pathology: Toward Strengthening the Critical Relationship.

The Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute collects data on cancer diagnoses, treatment, and survival for approximately 30% of the United States (US) population. To reflect advances in research and oncology practice, approaches to cancer control are evolving from simply enumerating the development of cancers by organ site in populations to including monitoring of cancer occurrence by histopathologic and molecular subtype, as defined by driver mutations and other alterations. SEER is an important population-based resource for understanding the implications of pathology diagnoses across demographic groups, geographic regions, and time and provides unique insights into the practice of oncology in the US that are not attainable from other sources. It provides incidence, survival, and mortality data for histopathologic cancer subtypes, and data by molecular subtyping are expanding. The program is developing systems to capture additional biomarker data, results from special populations, and expand biospecimen banking to enable cutting-edge cancer research and oncology practice. Pathology has always been central and critical to the effectiveness of SEER, and strengthening this relationship in this modern era of cancer diagnosis could be mutually beneficial. Achieving this goal requires close interactions between pathologists and the SEER program. This review provides a brief overview of SEER, focuses on facets relevant to pathology practice and research, and highlights the opportunities and challenges for pathologists to benefit from and enhance the value of SEER data.

Tumor del estroma gastrointestinal. Puesta al día / Gastrointestinal stromal tumor. An update

El tumor del estroma gastrointestinal (GIST) es la neoplasia mesenquimal gastrointestinal más frecuente. Desde el descubrimiento de la inmunoexpresión de c-KIT y la existencia de mutaciones en KIT y PDGFRA ha sido un ejemplo de terapia molecular dirigida que permitió la aplicación de un tratamiento, el mesilato de imatinib, altamente eficaz. Desde entonces hay evidencia de que en realidad el GIST constituye un grupo heterogéneo desde el punto de vista clínico, morfológico, inmunohistoquímico y molecular. Esta variabilidad puede implicar distintos acercamientos diagnósticos y terapéuticos para cada caso particular, por lo que se debe establecer cuando hay que realizar estudio molecular. Es también imprescindible valorar el riesgo de recurrencia y metástasis para establecer un correcto pronóstico y por la posibilidad de utilizar terapia adyuvante. En este artículo se revisan tanto las características clínicas, morfológicas, inmunohistoquímicas y moleculares del GIST atendiendo a su complejidad, como la correcta valoración del riesgo (AU)

Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal mesenchymal neoplasm. Since the discovery of c-KIT immunoexpression and the presence of KIT and PDGFRA mutations, it has represented an example of molecular targeted therapy that allowed the use of a highly effective treatment: imatinib mesylate. Since then there is evidence that GIST actually constitute a rather heterogeneous group from the clinical, morphological, immunohistochemical and molecular point of view. This variability may imply possible different diagnostic and therapeutic approaches for each specific case, making necessary to establish when molecular analyses must be performed. Is also mandatory to evaluate the risk of recurrence and metastases not only to know the prognosis but because adjuvant therapy may be used. n this paper the clinical, morphological, immunohistochemical and molecular features of GIST and the correct evaluation of risk are reviewed attending to its complexity (AU)

[Pathology- a new revival].

The field of pathology has undergone considerable change in recent years. The editor and editorial board of this journal are to be commended for their decision to devote a special issue to the field of pathology. Pathology deals with the characterization, investigation, and diagnosis of disease and disease processes and as such, has Long been considered one of the foundations of medicine. It is a rich and multi-faceted field which has retained its breadth of scope in the face of ever-increasing specialization and sub-specialization in medicine. In addition to its classic roles in autopsy, case description, and the diagnosis of pathoLogic processes, new and innovative spheres of activity are becoming integral to the field, especially in the realm of molecular pathology. Pathology is a Leading player in the new age of "personalized cancer therapy", where pathologists are responsible not only for diagnosing disease in the tissue, but also for conducting additional tests which may predict its response to specific drug therapies. In this context, moLecular pathology has become essential to the field both in the provision of cLinical service and research. To fully implement this trend, we are witness to the rise of tissue collection and tissue banking initiatives for both diagnostic and research purposes. A national tissue banking project in Israel has recently received considerable attention.

[Molecular pathology - aspects in KRAS mutation analysis in colon carcinoma].

Recent advances in understanding the molecular basis of cancer have led to the development of novel targeted therapies. The advantage of these therapies lies in their increased efficiency and reduced adverse events as compared to classicaL chemotherapy. One of these novel treatments is antibodies directed against Epidermal Growth Factor Receptor for colorectal carcinoma (CRC). Apparently, this treatment is only effective in patients whose tumor carries a wild-type copy of KRAS. Therefore, treatment decision in patients with CRC is based on molecular pathoLogical examination of the tumor tissue. Molecular testing for KRAS mutation in CRC carries new challenges. As opposed to germ-line mutations, which are present in all the cells, most of the mutations in cancer are somatic and present only in the tumor cells. This might make the diagnosis more difficult since the tumor tissue contains the tumor cells as well as stromal and inflammatory cells. Choosing an area that contains a smaller fraction of tumor cells might Lead to false negative results in the moLecular diagnosis. Identification of a tumor-rich area by a pathologist, who also determines the tumor cell fraction and chooses a test modality with the required sensitivity, will reduce the risk for such mistakes. Another issue that requires attention is intra-tumor heterogeneity. Recent reports have demonstrated that tumor cell population contains several sub-groups with differences in their mutational status. This phenomenon might affect the treatment choice and patients' response to therapy. However, recent reports in the literature indicate relative homogeneity for KRAS mutational status in CRC. In summary, molecular pathology is a new and rapidly evolving field chaLLenging pathologists involved in cancer diagnosis. It is crucial to make sure that the testing would be carried out in specialized centers that can address the molecular, as well as the histo-pathological aspects of the disease, to allow accurate diagnoses of high quality.

Forces driving change in medical diagnostics.

This article reviews the external forces that affect and shape the future of medical diagnostics. A PESTELI model is retrospectively used to highlight the factors that drive change at an operational and management level. The author describes the future picture of clinical laboratory diagnostics and proposes ways to overcome current and pending challenges on clinical laboratories and university curriculum. An international committee with broad expertise in clinical laboratory diagnostics is proposed to examine these changes and provide guidance.

Recomendaciones para la determinación de mutaciones de K-RAS en cáncer de colon / Guideliness for kras gene mutations testing in colorrectal cancer

Las determinaciones de mutaciones en el gen KRAS en el cáncer colorrectal en España se han venido realizando de manera sistemática en relativamente pocos centros, o bien se han realizado en un contexto de ensayo clínico. No obstante, gracias a la implementación de nuevas herramientas terapéuticas basadas en anticuerpos monoclonales frente al EGFR, el conocimiento del estado mutacional de KRAS es hoy en día un factor clave para la toma de decisiones terapéuticas debido a su valor predictivo negativo de respuesta al uso de dichos tratamientos. Este hecho ha potenciado la necesidad de la implementación de dichas determinaciones en la mayoría de los servicios de Anatomía Patológica de una manera estandarizada dentro de la práctica asistencial. Esta revisión propone una serie de recomendaciones generales con el fin de estandarizar la determinación de las mutaciones de KRAS, exponiendo los diferentes métodos técnicos disponibles, sus características y los aspectos clínicos relacionados, que serán de interés a la hora de incorporar dichas determinaciones en la rutina asistencial(AU)

Various centres in Spain systematically perform mutational status analyses of KRAS in colorectal cancer, some of which are related to various clinical trials. However, in the light of the use of anti-EGFR monoclonal antibodies in the treatment of colorectal cancer, the predictive value of KRAS has become a key factor in therapeutic decision making. Thus there is a growing necessity for the implantation of a standardized method of KRAS mutation analysis in the majority of pathology laboratories. The characteristics and associated clinical aspects of the different techniques available are reviewed and general recommendations for the standardization of KRAS mutation analysis are proposed(AU)

Consensus of the Spanish Society of Medical Oncology (SEOM) and Spanish Society of Pathology (SEAP) for HER2 testing in gastric carcinoma

The identification of HER2 alterations in advanced gastric carcinomas is of critical importance in daily clinical practice as such neoplasms require specific treatment with trastuzumab. For these reasons, pathologists and oncologists with expertise in gastric carcinomas and HER2 testing from both organisations (SEAP and SEOM) have endeavoured to discuss and agree on national guidelines for HER2 testing in gastric carcinomas. These guidelines are based on the experience of those who participated in the discussions and also on experience published internationally. These agreed guidelines give the minimum requirements that a pathological anatomy laboratory must fulfil in order to guarantee adequate HER2 testing in daily practice. Any laboratories which do not meet the minimum standards set out in the guidelines must make every effort to achieve compliance (AU)

Consensus of the Spanish Society of Medical Oncology (SEOM) and Spanish Society of Pathology (SEAP) for HER2 testing in gastric carcinoma.

The identification of HER2 alterations in advanced gastric carcinomas is of critical importance in daily clinical practice as such neoplasms require specific treatment with trastuzumab. For these reasons, pathologists and oncologists with expertise in gastric carcinomas and HER2 testing from both organisations (SEAP and SEOM) have endeavoured to discuss and agree on national guidelines for HER2 testing in gastric carcinomas. These guidelines are based on the experience of those who participated in the discussions and also on experience published internationally. These agreed guidelines give the minimum requirements that a pathological anatomy laboratory must fulfil in order to guarantee adequate HER2 testing in daily practice. Any laboratories which do not meet the minimum standards set out in the guidelines must make every effort to achieve compliance.

Establishment of the Australian in situ hybridization program for the assessment of HER2 amplification in breast cancer: a model for the introduction of new biomarkers into clinical practice.

In August 2006, the Australian government announced a decision to subsidize trastuzumab therapy for early breast cancer, to commence 6 weeks later. It was mandated that HER2 gene amplification, determined by in situ hybridization (ISH), be shown, and that the sponsor company, Roche Products Pty Ltd, should fund this testing. This announcement potentially required provision of ISH testing for HER2 for every newly diagnosed breast cancer, where previously HER2 testing had been performed by immunohistochemistry with support from a single fluorescence ISH (FISH) reference laboratory for indeterminate cases. The Australian HER2 Testing Advisory Board, an independent expert group, responded to the challenge of rapidly providing accurate nationwide ISH testing. Bright-field ISH was selected as the testing platform and a decentralized testing model, with support from a central FISH laboratory, was adopted. An implementation plan was developed addressing standards for training, accreditation, and quality assurance. Within 6 weeks, 8 pathology laboratories were accredited for ISH testing and by September 2008, 2 years after the announcement, 22 ISH testing laboratories were taking part in the national program and almost 20,000 ISH tests had been performed. This article describes the design and rapid implementation of a nationwide program of bright-field ISH as the first-line testing platform for HER2 status in early breast cancer. We believe that this model for the coordinated and large-scale implementation of a new biomarker test has wide application, given that accurate assessment of a range of novel biomarkers is being used increasingly to determine eligibility for new targeted treatment modalities.

Myelodysplastic syndromes: an update on molecular pathology

The myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterised by impaired peripheral blood cell production due to bone marrow dysplasia affecting one or more of the major myeloid cell lines. MDS are one of five major categories of myeloid neoplasms according to the World Health Organization (WHO) classification system for haematological cancers. Given their cytological and cytogenetic heterogeneity, these diseases probably constitute a group of molecularly distinct entities with variable degrees of ineffective haematopoiesis and susceptibility to leukaemic transformation. Recent studies provide some insights into the physiopathology of MDS. In the early stages, one mechanism contributing to hypercellular marrow and peripheral blood cytopenia is a significant increase in programmed cell death (apoptosis) in haematopoietic cells. Furthermore, altered responses in relation to cytokines, the immune system and bone marrow stroma also contribute to the disease phenotype. Deletions of chromosome 5q31-q32 are the most common recurring cytogenetic abnormalities detected in MDS. The 5q- syndrome is a new entity recognised in the WHO classification since 2001 and is associated with a good prognosis. Haploinsufficiency of multiple genes mapping to the common deleted region at 5q31-32 may contribute to the pathogenesis of 5q- syndrome and other MDS with 5q- deletion. Many studies have demonstrated that altered DNA methylation and histone acetylation can alter gene transcription. Abnormal methylation of transcription promoter sites is universal in patients with MDS, and the number of involved loci is increased in high-risk disease and secondary leukaemias. A better understanding of the pathogenesis of MDS can contribute to the development of new treatments such as hypomethylating drugs, immunomodulatory agents such as lenalidomide, and immunosuppressive drugs aimed at reversing the specific alteration that results in improvement in patients with MDS (AU)