Expression Patterns of ER, PR, HER-2/neu and p53 in Association with Nottingham Tumour Grade in Breast Cancer Patients.

Objectives: Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade. Methods: In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53. Results: Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed. Conclusion: Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER-2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.

Understanding the Complex Milieu of Epithelial-Mesenchymal Transition in Cancer Metastasis: New Insight Into the Roles of Transcription Factors.

Epithelial-mesenchymal transition (EMT) is a physiological program during which polarised, immobile epithelial cells lose connection with their neighbours and are converted to migratory mesenchymal phenotype. Mechanistically, EMT occurs via a series of genetic and cellular events leading to the repression of epithelial-associated markers and upregulation of mesenchymal-associated markers. EMT is very crucial for many biological processes such as embryogenesis and ontogenesis during human development, and again it plays a significant role in wound healing during a programmed replacement of the damaged tissues. However, this process is often hijacked in pathological conditions such as tumour metastasis, which constitutes the most significant drawback in the fight against cancer, accounting for about 90% of cancer-associated mortality globally. Worse still, metastatic tumours are not only challenging to treat with the available conventional radiotherapy and surgical interventions but also resistant to several cytotoxic agents during treatment, owing to their anatomically diffuse localisation in the body system. As the quest to find an effective method of addressing metastasis in cancer intervention heightens, understanding the molecular interplay involving the signalling pathways, downstream effectors, and their interactions with the EMT would be an important requisite while the challenges of metastasis continue to punctuate. Unfortunately, the molecular underpinnings that govern this process remain to be completely illuminated. However, it is becoming increasingly clear that EMT, which initiates every episode of metastasis, significantly requires some master regulators called EMT transcription factors (EMT-TFs). Thus, this review critically examines the roles of TFs as drivers of molecular rewiring that lead to tumour initiation, progression, EMT, metastasis, and colonisation. In addition, it discusses the interaction of various signalling molecules and effector proteins with these factors. It also provides insight into promising therapeutic targets that may inhibit the metastatic process to overcome the limitation of "undruggable" cancer targets in therapeutic design and upturn the current spate of drug resistance. More so, it extends the discussion from the basic understanding of the EMT binary switch model, and ultimately unveiling the E/M cellular plasticity along a phenotypic spectrum via multiple trans-differentiations. It wraps up on how this knowledge update shapes the diagnostic and clinical approaches that may demand a potential shift in investigative paradigm using novel technologies such as single-cell analyses to improve overall patient survival.

Histological classification, grading, staging, and prognostic indexing of female breast cancer in an African population: A 10-year retrospective study.

BACKGROUND: Breast cancer (BC) is a heterogeneous disease characterized with diverse genetic and ethnic/racial variations that may influence tumor characteristics and prognosis. We studied different histological types of BC and their prognostic indicators in part of Southwestern Nigeria. MATERIALS AND METHODS: A 10-year retrospective study of archival tissue-paraffin blocks and records of surgical cases (documented as BCs) between January 2005 and December 2014 was done. Tumor classification was made after the World Health Organization guidelines. Modified Bloom-Richardson score and TNM staging system were used in grading and staging the tumors. Nottingham prognostic index was employed in scoring the prognosis. RESULTS: The mean age was 49.7 years (20-89 years). The age group from 50 to 59 years was most affected. Out of 343 total cases, the most common histological type was invasive ductal carcinoma of no special type (88.9%). The majority (51.9%) had tumor sizes ranging 2-5 cm (pT2) and some (39.1%) with >5 cm (pT3) were all at palpable stages. The tumors were mostly Grades II and III types. Observation for lymph node metastasis confirmed that 261 (76.1%) were pN0 (negative), 77 (22.4%) were pN1, and 5 (1.5%) were pN2. Prediction of a chance of survival showed moderate prognosis in the majority (48.7%) of the cases. CONCLUSION: Although early detection of BC in this region was considerably poor, there was a better outcome compared with some other black populations. Clinical presentation, histological type, and prognostic indices varied from existing reports in many ethnic/racial groups. Indexing of BC pattern on a regional standpoint may serve a new direction toward better management considering the associated geographic disparity.