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.

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.

Clinical utility of kallikrein-related peptidases (KLK) in urogenital malignancies

2013 ◽  
Vol 110 (09) ◽  
pp. 408-422 ◽  
Author(s):  
Julia Dorn ◽  
Jane Bayani ◽  
George M. Yousef ◽  
Feng Yang ◽  
Viktor Magdolen ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Clinical Utility ◽  
Molecular Classification ◽  
Urogenital Tract ◽  
Proteolytic System ◽  
Prediction Of Response ◽  
Normal Prostate ◽  
Diagnosis And Prognosis ◽  
Malignant State

SummaryKallikrein-related peptidases (KLK), which represent a major tissue-associated proteolytic system, stand for a rich source of biomarkers that may allow molecular classification, early diagnosis and prognosis of human malignancies as well as prediction of response or failure to cancer-directed drugs. International research points to an important role of certain KLKs in female and male urogenital tract malignancies, in addition to cancers of the lung, brain, skin, head and neck, and the gastrointestinal tract. Regarding the female/male urogenital tract, remarkably, all of the KLKs are expressed in the normal prostate, testis, and kidney whereas the uterus, the ovary, and the urinary bladder are expressing a limited number of KLKs only. Most of the information regarding KLK expression in tumour-affected organs is available for ovarian cancer; all of the 12 KLKs tested so far were found to be elevated in the malignant state, depicting them as valuable biomarkers to distinguish between the normal and the cancerous phenotype. In contrast, for kidney cancer, a series of KLKs was found to be downregulated, while other KLKs were not expressed. Evidently, depending on the type of cancer or cancer stage, individual KLKs may show characteristics of a Janus-faced behaviour, by either expanding or inhibiting cancer progression and metastasis.

scholarly journals Automated Analysis of Proliferating Cells Spatial Organisation Predicts Prognosis in Lung Neuroendocrine Neoplasms

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4875
Author(s):  
Matteo Bulloni ◽  
Giada Sandrini ◽  
Irene Stacchiotti ◽  
Massimo Barberis ◽  
Fiorella Calabrese ◽  
...  
Keyword(s):  
Automated Analysis ◽  
Labelling Index ◽  
Neuroendocrine Neoplasms ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Learning Framework ◽  
Diagnosis And Prognosis ◽  
Tumour Prognosis

Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome. Subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. Here, we propose a machine learning framework for tumour prognosis assessment based on a quantitative, automated and repeatable evaluation of the spatial distribution of cells immunohistochemically positive for the proliferation marker Ki-67, performed on the entire extent of high-resolution whole slide images. Combining features from the fields of graph theory, fractality analysis, stochastic geometry and information theory, we describe the topology of replicating cells and predict prognosis in a histology-independent way. We demonstrate how our approach outperforms the well-recognised prognostic role of Ki-67 Labelling Index on a multi-centre dataset comprising the most controversial lung NENs. Moreover, we show that our system identifies arrangement patterns in the cells positive for Ki-67 that appear independently of tumour subtyping. Strikingly, the subset of these features whose presence is also independent of the value of the Labelling Index and the density of Ki-67-positive cells prove to be especially relevant in discerning prognostic classes. These findings disclose a possible path for the future of grading and classification of NENs.

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.

Clinicopathologic Characteristics, CpG Island Methylator Phenotype, and BRAF Mutations in Microsatellite-Stable Colorectal Cancers Without Chromosomal Instability

2008 ◽  
Vol 132 (6) ◽  
pp. 958-964
Author(s):  
Sanjay Kakar ◽  
Guoren Deng ◽  
Vaibhav Sahai ◽  
Koji Matsuzaki ◽  
Hirofumi Tanaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Braf Mutation ◽  
Chromosomal Instability ◽  
Cpg Island ◽  
Adverse Outcomes ◽  
Colorectal Carcinogenesis ◽  
Cpg Island Methylator Phenotype ◽  
Braf Mutations ◽  
Methylator Phenotype

Abstract Context.—The 2 chief pathways implicated in colorectal carcinogenesis, microsatellite instability and chromosomal instability, are not present in 20% to 37% of cases. Objective.—To determine whether the CpG island methylator phenotype (CIMP) pathway, characterized by simultaneous methylation of several known tumor suppressor genes, is the principal underlying mechanism in cases without chromosomal or microsatellite instability, and to determine the significance of CIMP pathway and BRAF mutations in microsatellite-stable (MSS) cases. Design.—Clinicopathologic features and chromosomal instability status by loss of heterozygosity analysis were determined in 83 cases of colorectal cancer in which microsatellite instability, CIMP status, BRAF mutations, and KRAS mutations were previously known. Results.—Microsatellite instability was present in 14 cases (17%). Of the 69 MSS cases (83%), chromosomal instability manifested by LOH involving at least one locus was observed in 53 cases (64%). Hence, 16 (19%) of 83 colorectal cancer cases showed neither microsatellite instability nor chromosomal instability. These cases had a low incidence of CIMP (3/16; 19%) and BRAF mutation (1/16; 6%). The 5-year survival in these cases was significantly better compared with MSS cases with chromosomal instability (80% vs 54%, P = .02). BRAF mutations were identified in 10 MSS cases (15%). BRAF mutation in MSS cases correlated significantly with high-level chromosomal instability (P = .009) and poor 5-year survival (0% vs 70%, P < .001). Conclusions.—CIMP does not appear to play a key role in colorectal cancer without microsatellite instability and chromosomal instability. These cases have a better survival, probably related to absence of significant chromosomal instability. BRAF mutations in MSS cases are associated with high levels of chromosomal instability that are likely responsible for the adverse outcomes in these cases.

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