World Health Organization Classification of Tumours

MicroRNA (miRNA ) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.

MicroRNA signatures in human cancers

MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.

I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.

Oncomirs : microRNAs with a role in cancer

MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer

/pdf/oncomirs-micrornas-with-a-role-in-cancer-4ryo1mpf3s.pdf

Oncomirs — microRNAs with a role in cancer

To the Editor: The histogenesis of extramammary Paget disease (EMPD) has long been a subject of debate and controversy. Nowadays, it is generally agreed that at least two forms of the disease can be delineated, namely primary and secondary, with the latter representing secondary involvement from an underlying carcinoma originating most commonly in the lower gastrointestinal or urinary tract. As for the primary disease, skin adnexa (eccrine or apocrine glands), ectopic mammary glands, or pluripotential germinative cells in the epidermis and other structures have been implicated as a possible source of neoplastic cells. The recent description of vulvar Toker cells in the Journal by Drs. Willman, Golitz, and Fitzpatrick offers an attractive analogy with the breast, where a similar condition is referred to as mammary Paget disease (MPD). In this location, over 95% of cases of MPD are associated with an underlying ductal carcinoma, and the rest is thought to arise from Toker cells described in 1970. The same seems to be true for rare cases of Paget disease involving ectopic breast adjacent to a supernumerary nipple. We wonder why the same approach could not be applied for the anogenital area and the vulva in particular. This anatomic site contains structures that were originally variously called ectopic breast tissue, supernumerary breast tissue, and most recently, interpreted as anogenital mammary-like glands (MLG). These have been shown to be a normal constituent of this area, and lesions involving these structures have been demonstrated to manifest a striking homology with those seen in the breast. In this regard, the following question arises: why should EMPD differ from MPD histogenetically, if all anatomic conditions are so similar? Below are some lines to support the analogy. It is known that primary EMPD (without underlying carcinoma of internal organs) affects most often vulvar and perianal areas, where anogenital MLG are found in highest concentrations. There have been several documented cases of EMPD with an underlying ductal carcinoma involving anogenital MLG, and this is also in accordance with our experience (Fig. 1). EMPD has a notorious propensity for recurrences, and this can be partly explained by the presence of neoplastic cells residing in anogenital

Vulvar Toker Cells: The Long-awaited Missing Link: A Proposal for an Origin-based Histogenetic Classification of Extramammary Paget Disease

Myxoinflammatory fibroblastic sarcoma: a tumor not restricted to acral sites.

Multilocular thymic cysts with pseudoepitheliomatous hyperplasia.

Thymoma classification has remained for many years a troubled and contentious field. In recent years, the World Health Organization (WHO) presented a proposal for the histopathologic classification of thymic epithelial neoplasms that has been adopted as the standard by many pathologists throughout the world. Yet, controversy still exists regarding its validity, accuracy, usefulness, and reproducibility in routine clinical practice. This article reviews the basic criteria of the current WHO classification of thymoma, along with its weaknesses and limitations, and presents alternate proposals for the histopathologic approach to the classification of thymic epithelial neoplasms.

https://www.hemonc.theclinics.com/article/S0889-8588(08)00030-0/pdf

Histologic Classification of Thymoma: The World Health Organization and Beyond

In search of tumor suppressor genes in papillary thyroid carcinoma (PTC), we previously used gene expression profiling to identify genes underexpressed in tumor compared with paired unaffected tissue. While searching for loss of heterozygosity (LOH) in genomic regions harboring candidate tumor suppressor genes, we detected LOH in a approximately 20 kb region around marker D9S176. Several ESTs flanking D9S176 were underexpressed in PTC tumors, and for one of the ESTs, downregulation was highly associated with the activating BRAF mutation V600E, the most common genetic lesion in PTC. A novel gene, NAMA, (noncoding RNA associated with MAP kinase pathway and growth arrest) containing the affected EST was cloned and characterized. NAMA is weakly expressed in several human tissues, and the spliced forms are primarily detected in testis. Several characteristics of NAMA suggest that it is a nonprotein coding but functional RNA; it has no long open reading frames (ORFs); the exons exhibit low sequence identity in the evolutionarily conserved regions; it is inducible by knockdown of BRAF, inhibition of the MAP kinase pathway, growth arrest and DNA damage in cancer cell lines. We suggest that NAMA is a noncoding RNA associated with growth arrest.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.22701

Identification of a novel noncoding RNA gene, NAMA, that is downregulated in papillary thyroid carcinoma with BRAF mutation and associated with growth arrest.

Saul Suster

Papers

Vulvar Toker Cells: The Long-awaited Missing Link: A Proposal for an Origin-based Histogenetic Classification of Extramammary Paget Disease

Myxoinflammatory fibroblastic sarcoma: a tumor not restricted to acral sites.

Multilocular thymic cysts with pseudoepitheliomatous hyperplasia.

Histologic Classification of Thymoma: The World Health Organization and Beyond

Identification of a novel noncoding RNA gene, NAMA, that is downregulated in papillary thyroid carcinoma with BRAF mutation and associated with growth arrest.