Molecular testing in endometrial carcinoma – joint recommendation of Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists

2021 ◽  
Vol 86 (4) ◽  
pp. 264-272
Author(s):  
Pavel Dundr ◽  
◽  
David Cibula ◽  
Martin Doležel ◽  
Pavel Fabián ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
European Society ◽  
Radiation Oncology ◽  
Molecular Classification ◽  
World Health ◽  
Molecular Testing ◽  
Therapeutic Implications ◽  
Health Organization ◽  
Endometrial Carcinomas

Summary: Molecular classification of endometrial carcinoma is becoming an important part of the dia gnostic process with direct therapeutic implications. Recent international guidelines, including the joint recommendation of the European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology and the European Society of Pathology include the molecular classification into standard diagnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th edition) of the World Health Organization classification of female genital tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of the Czech Medical Association of J. E. Purkyně (the Czech Oncological Society, the Oncogynecological Section of the Czech Gynecological and Obstetrical Society, the Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. Recommendation for molecular testing of endometrial carcinoma in routine dia gnostic practice in the Czech Republic.

Diagnostic utility and prognostic performance of a 92-gene cancer classifier to molecularly profile periampullary adenocarcinomas.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 197-197 ◽  
Author(s):  
Michael J. Overman ◽  
Huamin Wang ◽  
Catherine A. Schnabel ◽  
Jeff Anderson ◽  
Mark G. Erlander ◽  
...  
Keyword(s):  
Molecular Classification ◽  
Good Prognosis ◽  
Molecular Profile ◽  
Molecular Testing ◽  
Diagnostic Utility ◽  
Prognostic Performance ◽  
Therapeutic Implications ◽  
Rna Profiling ◽  
Gene Assay

197 Background: Due to the small anatomic size, multiplicity of epitheliums, and suboptimal diagnostics determining the site of origin of periampullary adenocarcinomas (PAA) is a challenge. We investigated the ability of a 92-gene RT-PCR assay (CancerTYPE ID) to categorize PAA and to prognostically stratify ampullary adenocarcinomas. Methods: 45 PAA patients who underwent pancreaticoduodenectomies were included; samples were histopathologically verified for tumor subtype determination (pancreatic, extrahepatic biliary, ampullary, or duodenal). Blinded FFPE tumor sections underwent molecular testing and were compared for concordance to histopathological tumor types and prognostic performance. 28 of these samples had previously undergone whole-genome RNA profiling (Overman et al. GI ASCO 2011 a161). Results: Molecular classification of 43 (96%) evaluable samples (13 ampullary, 10 pancreatic, 10 biliary, 10 duodenal) showed 91% concordance: ampullary [5 intestinal (int), 7 pancreaticobiliary (pb)], pancreatic [10 pb], duodenal [3 int, 7 gastroesophageal (ge)], biliary [7 pb]. The 92-gene assay was prognostic with a median OS of 70 m for ge/int cases vs. 32 m for pb cases, P=0.05. Discordant classifications were ge for 1 ampullary and 2 biliary samples, and ovary for 1 biliary case. Previous unsupervised RNA hierarchical clustering of all 13 ampullary cases had identified two prognostic groups (a good-prognosis int-like and a poor-prognosis pb-like), which were identical to the 92-gene classification for 12 cases (5 int and 7 pb). These two ampullary subgroups were prognostic with median OS of 63 vs. 24 m, P=0.07, respectively. Conclusions: The 92-gene assay demonstrated diagnostic utility for molecular site-of-origin classification of PAA. These results support exploration of this approach for the management of metastatic PAA (in which pathologic review of a primary resection specimen is not an option). Molecular classification of ampullary adenocarcinomas into intestinal and pancreaticobiliary subgroups is prognostically relevant; these and the gastric-like molecular profile of duodenal adenocarcinomas may have therapeutic implications.

scholarly journals Reproducibility of Malignant Pleural Mesothelioma Histopathologic Subtyping

2018 ◽  
Vol 142 (6) ◽  
pp. 747-752 ◽  
Author(s):  
Luka Brcic ◽  
Gregor Vlacic ◽  
Franz Quehenberger ◽  
Izidor Kern
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Interobserver Agreement ◽  
World Health ◽  
Pleural Mesothelioma ◽  
Therapeutic Implications ◽  
Histologic Pattern ◽  
Histologic Differentiation ◽  
Health Organization ◽  
Hematoxylin Eosin

Context.— Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis. Several studies have analyzed potential prognostic markers, but histologic type remains the single most important prognostic factor. Histologic subtypes of epithelioid MPM seem to have prognostic and therapeutic implications. Interobserver agreement in histologic pattern classification should be high. Objective.— To assess interobserver and intraobserver reproducibility in histologic differentiation between the main types of MPMs, and in further subtyping of epithelioid-type mesothelioma. Design.— One representative hematoxylin-eosin–stained slide was selected from the archive for each of 200 patients with MPM. They were reviewed independently by 3 pathologists and classified according to the current World Health Organization classification of pleural tumors. After the first round of evaluations, a consensus meeting was organized where problems were addressed and representative images for each histologic category were selected. Two months later, cases were reevaluated by all 3 pathologists. Results.— After the first round, overall interobserver agreement for histologic subtyping of mesothelioma was fair (κ, 0.36). The agreement was increased to substantial (κ, 0.63) in the second round. Improvement was found in interobserver agreement for all types of MPM and for most epithelioid subtypes. Conclusions.— Moderate to substantial agreement in histologic typing and subtyping of MPM can be achieved. However, training with additional clarification of diagnostic criteria, their strict application, and help from consensus-based illustrative images is needed.

scholarly journals Molecular Classification of Soft Tissue and Bone Tumors

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2326
Author(s):  
David Creytens
Keyword(s):  
Soft Tissue ◽  
World Health Organization ◽  
Bone Tumors ◽  
Who Classification ◽  
Molecular Classification ◽  
World Health ◽  
The World ◽  
Classification Of Tumors ◽  
Health Organization

Soft tissue and bone tumors constitute a large and heterogeneous group of tumors comprising >100 distinct histological types and subtypes, which are diagnosed and classified using criteria from the World Health Organization (WHO) Classification of Tumors [...]

scholarly journals What is New in 2019 World Health Organization (WHO) Classification of Tumors of the Digestive System: Review of Selected Updates on Neuroendocrine Neoplasms, Appendiceal Tumors, and Molecular Testing

2020 ◽  
Author(s):  
Naziheh Assarzadegan ◽  
Elizabeth Montgomery
Keyword(s):  
World Health Organization ◽  
Digestive System ◽  
English Literature ◽  
World Health ◽  
Response To Treatment ◽  
Neuroendocrine Neoplasms ◽  
Molecular Testing ◽  
Classification Of Tumors ◽  
Health Organization

Context.— The 5th edition of the World Health Organization classification of digestive system tumors discusses several advancements and developments in understanding the etiology, pathogenesis, and diagnosis of several digestive tract tumors. Objective.— To provide a summary of the updates with a focus on neuroendocrine neoplasms, appendiceal tumors, and the molecular advances in tumors of the digestive system. Data Sources.— English literature and personal experiences. Conclusions.— Some of the particularly important updates in the 5th edition are the alterations made in the classification of neuroendocrine neoplasms, understanding of pathogenesis of appendiceal tumors and their precursor lesions, and the expanded role of molecular pathology in establishing an accurate diagnosis or predicting prognosis and response to treatment.

Diagnostic utility and prognostic performance of a 92-gene cancer classifier to molecularly profile periampullary adenocarcinomas (PAA).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4133-4133
Author(s):  
Michael J. Overman ◽  
Huamin Wang ◽  
Catherine A. Schnabel ◽  
Jeffrey Anderson ◽  
Mark G. Erlander ◽  
...  
Keyword(s):  
Molecular Classification ◽  
Good Prognosis ◽  
Molecular Profile ◽  
Molecular Testing ◽  
Diagnostic Utility ◽  
Prognostic Performance ◽  
Therapeutic Implications ◽  
Gene Assay ◽  
Ffpe Tumor

4133 Background: Due to the small anatomic size, multiplicity of epitheliums, and suboptimal diagnostics determining the site of origin of PAA is a challenge. We investigated the ability of a 92-gene RT-PCR assay (CancerTYPE ID) to categorize PAA and to prognostically stratify ampullary adenocarcinomas. Methods: 171 PAA patients who underwent pancreaticoduodenectomies were included; samples were histopathologically verified for tumor subtype determination: pancreatic (PAN), extrahepatic biliary (EB), ampullary (AMP), or duodenal (DOUD). Blinded FFPE tumor sections underwent molecular testing. Analytical sets were an initial 45 PAA set evaluating concordance to histopathological tumor types and prognostic performance, and a second set of 126 AMP and DOUD adenocarcinoma for validation of prognostic performance. Results: Of the initial 45 patient cohort, molecular classification of 43 (96%) evaluable samples (13 AMP, 10 PAN, 10 EB, 10 DOUD) showed 91% concordance: AMP [5 intestinal (int), 7 pancreaticobiliary (pb)], PAN [10 pb], DOUD [3 int, 7 gastroesophageal (ge)], EB [7 pb]. The 92-gene assay was prognostic with a median OS of 70 m for ge/int cases vs. 32 m for pb cases, P=0.05. Discordant classifications were ge for 1 AMP and 2 EB samples, and ovary for 1 EB case. Previous unsupervised RNA hierarchical clustering (Overman GI ASCO 2011 a161) of all 13 AMP cases had identified two prognostic groups (a good-prognosis int-like and a poor-prognosis pb-like), which were identical to the 92-gene classification for 12 of the 13 cases. Conclusions: In the initial cohort of 45 patients, the 92-gene assay demonstrated diagnostic utility for molecular site-of-origin classification of PAA; evaluation of the remaining 126 ampullary and duodenal cases will be presented. Results support exploration of this approach for the management of metastatic PAA (in which pathologic review of a primary resection specimen is not an option). Molecular classification of ampullary adenocarcinomas into intestinal and pancreaticobiliary subgroups is prognostically relevant; these and the gastric-like molecular profile of duodenal adenocarcinomas may have therapeutic implications.

Molecular Genetics of Endometrial Carcinoma

2019 ◽  
Vol 14 (1) ◽  
pp. 339-367 ◽  
Author(s):  
Daphne W. Bell ◽  
Lora Hedrick Ellenson
Keyword(s):  
Endometrial Carcinoma ◽  
Copy Number ◽  
Clear Cell ◽  
Genomic Analysis ◽  
Molecular Classification ◽  
The United States ◽  
The Cancer Genome Atlas ◽  
Therapeutic Implications ◽  
Molecular Features ◽  
Endometrial Carcinomas

Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Endometrioid endometrial carcinomas constitute approximately 85% of newly diagnosed cases; serous carcinomas represent approximately 3–10% of diagnoses; clear cell carcinoma accounts for <5% of diagnoses; and uterine carcinosarcomas are rare, biphasic tumors. Longstanding molecular observations implicate PTEN inactivation as a major driver of endometrioid carcinomas; TP53 inactivation as a major driver of most serous carcinomas, some high-grade endometrioid carcinomas, and many uterine carcinosarcomas; and inactivation of either gene as drivers of some clear cell carcinomas. In the past decade, targeted gene and exome sequencing have uncovered additional pathogenic aberrations in each histotype. Moreover, an integrated genomic analysis by The Cancer Genome Atlas (TCGA) resulted in the molecular classification of endometrioid and serous carcinomas into four distinct subgroups, POLE (ultramutated), microsatellite instability (hypermutated), copy number low (endometrioid), and copy number high (serous-like). In this review, we provide an overview of the major molecular features of the aforementioned histopathological subtypes and TCGA subgroups and discuss potential prognostic and therapeutic implications for endometrial carcinoma.

scholarly journals Practical Applications in Immunohistochemistry: An Immunophenotypic Approach to the Spleen

2019 ◽  
Vol 143 (9) ◽  
pp. 1093-1105
Author(s):  
William R. Borch ◽  
Nadine S. Aguilera ◽  
Mark D. Brissette ◽  
Dennis P. O'Malley ◽  
Aaron Auerbach
Keyword(s):  
English Language ◽  
World Health ◽  
Molecular Testing ◽  
Splenic Marginal Zone Lymphoma ◽  
Littoral Cell ◽  
Practical Applications ◽  
Normal Spleen ◽  
Health Organization ◽  
Hematoxylin Eosin

Context.— Even though immunohistochemistry is routinely used by pathologists, evaluation of immunohistochemistry in splenic lesions remains difficult for many. Classification of benign and splenic lesions often requires a combination of hematoxylin-eosin evaluation, immunophenotyping, and sometimes molecular testing. Immunohistochemical staining is essential in evaluating many splenic lesions, and requires an understanding of the normal compartments of the spleen. Objective.— To address different immunohistochemical features used for identification and subclassification of different lesions of the spleen, as well as in the normal compartments of the spleen. Data Sources.— The information outlined in this review article is based on our experiences with a variety of spleen cases, on the current World Health Organization classification of hematopoietic and lymphoid tumors, and on a review of English-language articles published during 2018. Conclusions.— Features for phenotyping normal spleen as well as a variety of splenic lesions, including littoral cell angioma and splenic marginal zone lymphoma, are discussed. Suggested immunopanels are provided to assist in the diagnosis of different lesions of the spleen.

Diffuse Leptomeningeal Glioneuronal Tumor in a 4.5-year-old Girl: A Case Report and Review of the Literature

2020 ◽  
Author(s):  
Anna Gabryś ◽  
Julia Kuzaj ◽  
Dominika Pawełczak ◽  
Katarzyna Seliga ◽  
Agnieszka Jelińska ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
World Health ◽  
Glioneuronal Tumor ◽  
Molecular Testing ◽  
Diffuse Leptomeningeal Glioneuronal Tumor ◽  
History Of ◽  
The Central Nervous System ◽  
Classification Of Tumors ◽  
Health Organization

AbstractDiffuse leptomeningeal glioneuronal tumor (DLGNT) is an entity introduced in 2016 World Health Organization classification of tumors of the central nervous system. The tumor occurs very rarely. Due to the lack of specific clinical and radiological features, biopsy is necessary to be performed and histological and immunohistochemical testing is essential to reach the diagnosis. A 4.5-year-old girl presented with a history of headache, vomiting, and right eye convergent squint. Imaging revealed multiple enhancing lesions located supra- and infratentorially and intramedullary. Histopathological examination demonstrated diffused growth of neoplastic cells. Molecular testing revealed KIAA1549-BRAF fusion and the diagnosis of DLGNT was stated.

Identification of TP53 mutated group using a molecular and immunohistochemical classification of endometrial carcinoma to improve prognostic evaluation for adjuvant treatments

2020 ◽  
Vol 30 (5) ◽  
pp. 640-647
Author(s):  
Guillaume Beinse ◽  
Bastien Rance ◽  
Pierre-Alexandre Just ◽  
Brigitte Izac ◽  
Franck Letourneur ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Endometrial Carcinoma ◽  
Mismatch Repair ◽  
European Society ◽  
Molecular Classification ◽  
Next Generation ◽  
Clinical Risk ◽  
Generation Sequencing ◽  
Risk Of Relapse

IntroductionMolecular classification of endometrial carcinoma has been proposed to predict survival. However, its role in patient management remains to be determined. We aimed to identify whether a molecular and immunohistochemical classification of endometrial carcinoma could improve decision-making for adjuvant therapy.MethodsAll consecutive patients treated for endometrial carcinoma between 2010 and 2017 at Cochin University Hospital were included. Clinical risk of relapse was based on European Society for Medical Oncology-European Society of Gynaecological Oncology-European SocieTy for Radiotherapy & Oncology (ESMO-ESGO-ESTRO) consensus. The clinical event of interest was event-free survival. Formalin-fixed paraffin-embedded tissue samples were processed for histopathological analysis and DNA extraction. The nuclear expression of mismatch repair and TP53 proteins was analyzed by immunohistochemistry. Next-generation sequencing of a panel of 15 genes including TP53 and POLE was performed using Ampliseq panels on Ion Torrent PGM (ThermoFisher). Tumors were allocated into four molecular groups using a sequential method based on next-generation sequencing and immunohistochemistry data: (1) POLE/ultramutated-like; (2) MSI/hypermutated-like (mismatch repair-deficient); (3) TP53-mutated (without POLE mutations or mismatch repair deficiency); (4) not otherwise specified (the remaining tumors).Results159 patients were included; 125 tumors were available for molecular characterization and distributed as follows: (1) POLE/ultramutated-like: n=4 (3%); (2) MSI/hypermutated-like: n=35 (30%); (3) TP53-mutated: n=30 (25%); and (4) not otherwise specified: n=49 (42%). Assessing the TP53 status by immunohistochemistry only rather than next-generation sequencing would have misclassified 6 tumors (5%). TP53-mutated tumors were associated with poor prognosis, independently of International Federation of Gynecology and Obstetrics (FIGO) stage and histological grade (Cox-based adjusted hazard ratio (aHR) 5.54, 95% CI 2.30 to 13.4), and independently of clinical risk of relapse (aHR 3.92, 95% CI 1.59 to 9.64). Among patients with FIGO stage I–II tumors, 6 (38%) TP53-mutated tumors had low/intermediate clinical risk of relapse and did not receive adjuvant chemotherapy or radiotherapy.ConclusionEndometrial carcinoma molecular classification identified potentially under-treated patients with poor molecular prognosis despite being at low/intermediate clinical risk of relapse. Consideration of molecular classification in adjuvant therapeutic decisions should be evaluated in prospective trials.

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