J Oral Maxillofac Pathol 2014 Sep 18 Suppl 1 S2 S5 DOI 10410

J Oral Maxillofac Pathol 2014 Sep 18suppl 1 S2s5doi 1041030

J Oral Maxillofac Pathol 2014 Sep 18suppl 1 S2s5doi 1041030

Analyze the role of mitosis and its abnormalities in the context of oral pathology. Discuss the cell cycle phases, mechanisms regulating mitosis, and how abnormal mitotic figures contribute to oral neoplasms such as dysplasia and carcinoma. Incorporate recent advances in diagnostic techniques like immunohistochemistry, specifically anti-phosphohistone H3 antibodies, and examine their prognostic significance. Provide a comprehensive overview of the cellular mechanisms, pathological changes, and diagnostic implications related to mitosis in oral tissue pathology.

Paper For Above instruction

Introduction

Mitosis is a fundamental cellular process essential for growth, tissue repair, and maintenance of tissue homeostasis. Proper regulation of mitosis ensures accurate chromosome segregation, thereby preserving genetic stability. In oral pathology, abnormal mitosis plays a pivotal role in the development and progression of neoplastic lesions. This paper explores the cell cycle phases, the mechanisms regulating mitotic fidelity, and how mitotic abnormalities contribute to oral pre-malignant and malignant conditions. It further discusses the advances in diagnostic techniques, especially immunohistochemistry, that have enhanced our understanding of mitotic activity and its prognostic significance in oral lesions.

Cell Cycle and Mitosis

The cell cycle consists of interphase and mitosis. Interphase comprises G1, S, and G2 phases, during which the cell prepares for division by growing and duplicating genetic material (Sharma & Koul, 2011). The G1 phase ensures the cell is ready for DNA synthesis, and the G2 phase verifies the completeness of DNA replication before entering mitosis (Alberts et al., 2014). Mitosis, a highly regulated process, is subdivided into prophase, metaphase, anaphase, and telophase, leading to the formation of two genetically identical daughter cells (Fischer & Chen, 2010). Accurate execution of mitosis is governed by intricate checkpoints ensuring genomic integrity.

Mechanisms Regulating Mitosis

The progression through mitosis relies on spindle assembly, chromosome alignment, and segregation, orchestrated by the spindle assembly checkpoint (SAC) (Taylor & McGowan, 2010). The cyclin-dependent kinases (CDKs), especially CDK1 in association with Cyclin B, regulate the transition from G2 to M phase (Murray & Hunt, 1993). Spindle assembly, centromere function, and cohesion of sister chromatids are critical for precise chromosome segregation (Gadde & Heald, 2004). Any disruption in these regulatory mechanisms may result in aberrant mitosis, leading to aneuploidy and chromosomal instability—hallmarks of cancer (Funk & Kuppers, 2017).

Abnormal Mitosis in Oral Pathology

In pathological conditions, such as oral epithelial dysplasia and carcinoma, abnormal mitotic figures (MFs) are frequently observed (Regezi & Sciubba, 2012). These include multipolar mitoses, tripolar or tetrapolar divisions, and irregular chromosomal condensation, indicative of spindle defects, chromosome missegregation, or defective checkpoint control (Mendelsohn, 1935). Such abnormalities result in genomic instability, increased mutation rates, and tumor progression (Mugner et al., 2011). Histologically, these aberrant mitoses are vital criteria for grading dysplasia severity and malignancy potential (Lingen et al., 2002).

Diagnostic Techniques in Mitotic Abnormality Detection

The identification of mitotic figures traditionally involved hematoxylin and eosin (H&E) staining; however, it is often limited by interobserver variability and difficulty in discerning actual mitoses from apoptotic or degenerative cells (Ankle et al., 2007). Recent advances include immunohistochemical staining using anti-phosphohistone H3 (PHH3) antibodies, which specifically mark cells in mitosis by detecting phosphorylated histone H3 during cell division (Kim et al., 2007). This method provides a more accurate and objective measure of mitotic activity, aiding in prognosis and therapeutic decisions.

Prognostic Implications of Mitotic Abnormalities

High mitotic indices and the presence of atypical mitoses correlate with aggressive tumor behavior and poorer prognosis in oral squamous cell carcinoma (Gadde & Heald, 2004). The use of immunohistochemical markers like PHH3 enhances the assessment of mitotic activity, allowing for better stratification of malignant potential (Kim et al., 2007). Elevated mitotic rates reflect increased proliferative activity, while abnormal mitotic figures signify chromosomal instability, both serving as important prognostic indicators (Funk & Kuppers, 2017).

Role of Cancer Stem Cells and Asymmetric Cell Division

The cancer stem cell hypothesis suggests that a subset of tumor cells possesses self-renewal and differentiation capabilities (Reya et al., 2001). Asymmetric cell division, a process where a stem cell produces one identical stem cell and one differentiated progenitor, is crucial for tissue homeostasis (Sharma & Koul, 2011). Disruption of this balance can lead to excessive self-renewal and tumorigenesis (Shahriyari & Komarova, 2013). Aneuploidy and multipolar mitosis observed in tumors may result from defective asymmetric division, emphasizing the importance of proper mitotic control in preventing carcinogenesis.

Conclusion

Maintaining mitotic fidelity is vital for normal cellular function and tissue homeostasis. In oral pathology, abnormalities in mitosis contribute significantly to tumor initiation and progression through genomic instability and chromosomal aberrations. Advanced diagnostic techniques, especially immunohistochemistry targeting mitosis-specific proteins like PHH3, have enhanced our ability to assess proliferative activity and predict tumor behavior. Understanding the mechanisms underlying mitotic anomalies and their detection can inform targeted therapies and improve prognostication in oral neoplasms.

References

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