Kinan Drak Alsibai

By Kinan Drak Alsibai and Didier Meseure

Tumors appear as heterogeneous tissues that consist of tumor cells surrounding by a tumor microenvironment (TME). TME is a complex network composed of extracellular matrix (ECM), stromal cells, and immune/inflammatory cells that drive cancer cells fate from invasion to intravasation and metastasis. The stromal-inflammatory interface represents a dynamic space, in which exchange of numerous molecular information is associated with the transition into tumorigenic microenvironment. Recruitment, activation, and reprogramming of stromal and immune/inflammatory cells in the extracellular space are the consequences of a reciprocal interaction between TME and cancer cells. Recent data suggest that cancer development is influenced by TME and controlled by the host’s immune system, underlying the importance of TME components and immune biomarkers in the determination of prognosis and response to therapy. The immune classification has prognostic value and may be a useful supplement to the histopathological, molecular, and TNM classifications. Nevertheless, the complexity of quantitative immunohistochemistry and the variable assay protocols, stromal and immune cell types analyzed underscore the need to harmonize the quantified methods. It is therefore important to incorporate TME and immune scoring in determinations of cancer prognosis and to make sure they become a routine part of the histopathological diagnostic and prognostic assessment of patients.

Part of the book: Histopathology

By Didier Meseure and Kinan Drak Alsibai

Epigenetic abnormalities are early events in carcinogenesis and associate heterogeneity of DNA methylation, modifications of histones, and deregulation of noncoding RNAs. Aberrant expressions of PIWI proteins and piRNAs were recently observed in numerous subtypes of malignant tumors and were implicated in occurrence of most cancer hallmarks such as cell proliferation, genomic stability, apoptosis inhibition, invasion, and metastatic spread. However, this pathway is a new emerging research field, and further investigations are necessary to elucidate their oncogenic or tumor-suppressing status. Since the aberrant expression of this pathway may induce stemness, analysis of relationship between PIWI proteins, piRNAs, and cancer stem cells may open new avenues in cancer research. The objective of this review is to provide a broad overview of the emerging implication of PIWI proteins and piRNAs in carcinogenesis and their potential clinical interest as diagnostic and prognostic biomarkers and therapeutic tools.

Part of the book: Chromatin and Epigenetics

By Didier Meseure and Kinan Drak Alsibai

PiRNAs [P-element-induced wimpy testis (PIWI)-interacting RNAs] represent the most frequent but the least well-investigated subtype of small ncRNAs and are characterized by their interaction with PIWI proteins, a subclass of the Argonaute family. PiRNAs and PIWI proteins maintain integrity of the genomic structure and regulate gene expression in germline and somatic cells. The PIWI-piRNA pathway primarily constitutes a conserved immune-like surveillance process that recognizes self and nonself. This axis controls genome integrity of germline cells and nonaging somatic cells by silencing and suppressing propagation of transposable elements through epigenetic and posttranscriptional mechanisms. However, mounting evidences indicate that the PIWI-piRNA pathway has broader implications in both germinal and somatic cells in various physiological and pathological processes. It modulates mRNAs levels of expression, stability, turnover, and translation and interacts directly with many transcription factors and signaling pathways molecules. PIWI proteins and piRNAs play pivotal roles in germline stem cell maintenance and self-renewal, fertilization and development, genes and proteins expression, genome rearrangement, and homeostasis.

Part of the book: Chromatin and Epigenetics