Morphological and Molecular Classification of Human Cancer

2017 ◽  
Author(s):  
Mark E. Sherman ◽  
Melissa A. Troester ◽  
Katherine A. Hoadley ◽  
William F. Anderson
Keyword(s):  
Human Cancer ◽  
Molecular Classification ◽  
Tumor Stage ◽  
Cancer Surveillance ◽  
Molecular Profile ◽  
Malignant Neoplasms ◽  
Anatomic Site ◽  
Molecular Events ◽  
Classification Of Tumors

Accurate and reproducible classification of tumors is essential for clinical management, cancer surveillance, and studies of pathogenesis and etiology. Tumor classification has historically been based on the primary anatomic site or organ in which the tumor occurs and on its morphologic and histologic phenotype. While pathologic criteria are useful in predicting the average behavior of a group of tumors, histopathology alone cannot accurately predict the prognosis and treatment response of individual cancers. Traditional measures such as tumor stage and grade do not take into account molecular events that influence tumor aggressiveness or changes in the tumor composition during treatment. This chapter provides a primer on approaches that use pathology and molecular biology to classify and subclassify cancers. It describes the features of carcinomas, sarcomas, and malignant neoplasms of the immune system and blood, as well as various high-throughput genomic platforms that characterize the molecular profile of tumors.

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.

Toward a Molecular Classification of Melanoma

2007 ◽  
Vol 25 (12) ◽  
pp. 1606-1620 ◽  
Author(s):  
Leslie A. Fecher ◽  
Staci D. Cummings ◽  
Megan J. Keefe ◽  
Rhoda M. Alani
Keyword(s):  
Disease Onset ◽  
Molecular Classification ◽  
The United States ◽  
Genetic Studies ◽  
Activating Mutations ◽  
Molecular Events ◽  
Advanced Stages ◽  
Systemic Therapies

The incidence of melanoma is increasing at one of the highest rates of any form of cancer in the United States, with the current lifetime risk being one in 68. At present, there are limited systemic therapies to treat advanced stages of melanoma, and the key to improved survival remains early detection. Recent discoveries have allowed for a clearer picture of the molecular events leading to melanoma development and progression. Since identifying prevalent activating mutations of the BRAF kinase in melanomas, there has been a flood of additional molecular studies to further clarify the role of this pathway and others in melanomagenesis. In particular, recent genetic studies have demonstrated specific genotype-phenotype correlations that provide the first major insights into the molecular subclassification of melanoma and the heterogeneous nature of this malignancy. In this article, we review the most up-to-date molecular discoveries in melanoma biology and provide a framework for understanding their significance in melanoma development and progression. We also provide details on the development of novel therapies based on these recent molecular discoveries and insight into current and planned clinical trials. It is expected that these latest studies in melanoma will help define the critical molecular events involved in disease onset and progression and allow us to move rapidly toward a true molecular classification. We eagerly anticipate rationally designed melanoma therapies based on such a classification scheme and the associated improvements in patient outcomes.

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 Advanced MR techniques in glioblastoma imaging—upcoming challenges and how to face them

2021 ◽  
Author(s):  
Timo A. Auer
Keyword(s):  
Therapy Monitoring ◽  
Multiparametric Mri ◽  
Imaging Biomarkers ◽  
Molecular Profile ◽  
Key Points ◽  
The Central Nervous System ◽  
Classification Of Tumors ◽  
Noninvasive Characterization

Key Points• The management of gliomas has changed dramatically since the presentation of the revised WHO Classification of Tumors of the Central Nervous System in 2016 emphasizing the tumor heterogeneity based on their molecular profile.• The need for a more noninvasive characterization of glioblastomas (GBM) by establishing reliable imaging biomarkers to predict patient outcome and improve therapy monitoring is bigger than ever.• Multiparametric MRI, including promising newer techniques like electrical property tomography and mapping, may have the potential to provide enough information for intelligent imaging postprocessing algorithms to face the challenge by decoding GBM heterogeneity noninvasively.

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.

scholarly journals Colorectal carcinoma under microscopy: Patohistology or much more?

2012 ◽  
Vol 59 (2) ◽  
pp. 31-38
Author(s):  
Slavica Knezevic-Usaj ◽  
Tatjana Ivkovic-Kapicl ◽  
Milana Panjkovic ◽  
Istvan Klem ◽  
Zivka Eri
Keyword(s):  
Colorectal Carcinoma ◽  
Molecular Classification ◽  
Colorectal Carcinogenesis ◽  
Braf Mutations ◽  
Diagnosis And Prognosis ◽  
Predictive Parameters ◽  
Molecular Events ◽  
Methylator Phenotype

Today the role of pathologists is increasingly focused on finding more accurate prognostic and predictive parameters that will be necessary for targeted treatment of patients. Improving understanding of colorectal carcinogenesis allow us to consider incorporation of these new knowledges in molecular classification of colorectal cancer. There are different ways of molecular classification, but most of them are based on: 1. type of genetic instability; 2. methylator phenotype and 3. single molecular events such are KRAS and BRAF mutations. This review considers a new molecular classification of colorectal carcinoma proposed by J. Jass in 2007 which is based on the correlation of molecular and morphological features. We would also like to point out to the new role of pathologists in the era of personalized medicine in diagnosis and prognosis of colorectal carcinomas as well as in selection of patients for some modalities of targeted therapy.

Molecular Classification of 5-Amino-2-Aroylquinolines and 4-Aroyl-6,7,8-Trimethoxyquinolines as Highly Potent Tubulin Polymerization Inhibitors

2013 ◽  
Vol 3 (2) ◽  
pp. 1-26 ◽  
Author(s):  
Francisco Torrens ◽  
Gloria Castellano
Keyword(s):  
Cancer Cell ◽  
Information Entropy ◽  
Human Cancer ◽  
Selection Criterion ◽  
Chemical Properties ◽  
Cancer Cell Line ◽  
Molecular Classification ◽  
Human Cancer Cell Lines ◽  
Anti Cancer

Algorithms for classification and taxonomy are proposed based on criteria as information entropy and its production. It is classified a series of 5-amino-2-aroylquinolines (AAQs) and 4-aroyl-6,7,8-trimethoxyquinolines (TMQs) combretastatin analogues for anti-cancer activity. 5-Amino-6-methoxy-2-aroylquinoline AAQ showed anti-proliferative activity more potent as compared to combretastatin A-4 (CA4), against various human cancer cell lines and a multidrug resistance (MDR) cancer cell line. On the basis of AAQ/TMQ structure–activity relationship new derivatives are designed. The AAQs/TMQs are classified using nine characteristic chemical properties in molecules. Many classification algorithms are based on information entropy. When applying the procedures to sets of moderate size, an excessive number of results appear compatible with data and suffer a combinatorial explosion. However, after equipartition conjecture, one has a selection criterion between different variants resulting from classification between hierarchical trees. A classification of anti-cancer agents is obtained. The features denote positions R2–8 on the quinoline bicycle.

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