The leading role of pathology in assessing the somatic molecular alterations of cancer: Position Paper of the European Society of Pathology

Abstract

Molecular pathology is an essential part of pathology complementing conventional morphological tools to obtain a correct integrated diagnosis with appropriate assessment of prognosis and prediction of response to therapy, particularly in cancer. There is a concern about the situation of molecular pathology in some areas of Europe, namely, regarding the central role of pathologists in assessing somatic genomic alterations in cancer. In some countries, there are attempts that other laboratory medicine specialists perform the molecular analysis of somatic alterations in cancer, particularly now when next generation sequencing (NGS) is incorporated into clinical practice. In this scenario, pathologists may play just the role of "tissue providers," and other specialists may take the lead in molecular analysis. Geneticists and laboratory medicine specialists have all background and skills to perform genetic analysis of germline alterations in hereditary disorders, including familial forms of cancers. However, interpretation of somatic alterations of cancer belongs to the specific scientific domain of pathology. Pathologists are necessary to guarantee the quality of the results, for several reasons: (1) The identified molecular alterations should be interpreted in the appropriate morphologic context, since most of them are context-specific; (2) pre-analytical issues must be taken into consideration; (3) it is crucial to check the proportion of tumor cells in the sample subjected to analysis and presence of inflammatory infiltrate and necrosis should be monitored; and 4) the role of pathologists is crucial to select the most appropriate methods and to control the turnaround time in which the molecular results are delivered in the context of an integrated diagnosis. Obviously, there is the possibility of having core facilities for NGS in a hospital to perform the sequence analysis that are open to other specialties (microbiologists, geneticists), but also in this scenario, pathologists should have the lead in assessing somatic alterations of cancer. In this article, we emphasize the importance of interpreting somatic molecular alterations of the tumors in the context of morphology. In this Position Paper of the European Society of Pathology, we strongly support a central role of pathology departments in the process of analysis and interpretation of somatic molecular alterations in cancer.

Genetic alterations associated with multiple primary malignancies

“…To evaluate whether the genomic profiles (CNA and LOH) for tumors from the same patient were similar, three different analyses (hierarchical clustering, Similarity Index (SI), and clonality testing) were performed using the OncoScan data. Hierarchical clustering and SI were concordant for tumor pairs from eight (patients 03, 11, 13, 18, 20, 22, 23, and 26) and four 03,13,18 and 26 patients, which were classified as genomically similar using the CNA and LOH data, respectively (Figure 3). In contrast, clonality testing was only concordant with clustering and SI for four (patients 11, 18, 22, and 26) and three (patients 13, 18, and 26) patients.…”

“…Guidelines for the clinical management of cancer patients frequently include testing for somatic mutations and histopathologic markers 24–26 . However, we still need to have a better understanding of genetic alterations contributing to the development of OPPMs before a BC diagnosis.…”

“…Guidelines for the clinical management of cancer patients frequently include testing for somatic mutations and histopathologic markers. 24 , 25 , 26 However, we still need to have a better understanding of genetic alterations contributing to the development of OPPMs before a BC diagnosis. In the present study, we performed genome‐wide screening of the BC and OPPMs for 26 young women (≤50 years at the time of the BC diagnosis) to identify common DNA copy number alterations and somatic mutations in the tumor pairs.…”

Impact of Endoscopic Ultrasound-Guided Tissue Acquisition on Decision-Making in Precision Medicine for Pancreatic Cancer: Beyond Diagnosis

“…Furthermore, FFPE samples allow the tissue architecture to be preserved and can be used for future ancillary studies. However, FFPE samples subjected to inappropriate fixation methods (i.e., inappropriate duration of fixation or concentration of fixative) may yield incorrect results [ 90 , 92 ]. Furthermore, DNA extracted from FFPE tissues is generally damaged, and long-term storage may also affect the DNA quality.…”

Endocervical Adenocarcinoma, Gross Examination, and Processing, Including Intraoperative Evaluation: Recommendations From the International Society of Gynecological Pathologists

“…Hysterectomy specimens should be opened immediately upon receipt in the pathology laboratory and prepared for formalin-fixation in order to mitigate tissue autolysis, which may impair microscopic examination and/or immunohistochemical and molecular testing 43 – 46 . Even if the hysterectomy is received by the laboratory already in formalin, the endocervical and endometrial lining, as well as any tumor, are the least likely parts of the specimen to be exposed to the formalin if the uterus was not opened.…”