Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival.

PURPOSE: MMP9 is a matricellular protein associated with extracellular matrix (ECM) remodelling, that promotes tumour progression, and modulates the activity of cell adhesion molecules and cytokines. This study aims to assess the prognostic value of MMP9 and its association with cytoskeletal modulators in early-stage invasive breast cancer (BC). METHODS: MMP9 expression was evaluated by immunohistochemistry using a well-characterised series of primary BC patients with long-term clinical follow-up. Association with clinicopathological factors, patient outcome and ECM remodelling BC-biomarkers were investigated. METABRIC dataset, BC-GenExMiner v4.0 and TCGA were used for the external validation of MMP9 expression. GSEA gene enrichment analyses were used to evaluate MMP9 associated pathways. RESULTS: MMP9 immunopositivity was observed in the stroma and cytoplasm of BC cells. Elevated MMP9 protein levels were associated with high tumour grade, high Nottingham Prognostic Index, and hormonal receptor negativity. Elevated MMP9 protein expression correlated significantly with cytokeratin 17 (Ck17), Epidermal Growth Factor Receptor (EGFR), proliferation (Ki67) biomarkers, cell surface adhesion receptor (CD44) and cell division control protein 42 (CDC42). Cytoplasmic MMP9 expression was an independent prognostic factor associated with shorter BC-specific survival. In the external validation cohorts, MMP9 expression was also associated with poor patients' outcome. Transcriptomic analysis confirmed a positive association between MMP9 and ECM remodelling biomarkers. GSEA analysis supports MMP9 association with ECM and cytoskeletal pathways. CONCLUSION: This study provides evidence for the prognostic value of MMP9 in BC. Further functional studies to decipher the role of MMP9 and its association with cytoskeletal modulators in BC progression are warranted.

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer.

PURPOSE: The epithelial-mesenchymal transition (EMT) plays a key role in breast cancer progression and metastasis. Lipocalin 2 (LCN2) is involved in the regulation of EMT. The aim of this study was to investigate the clinicopathological significance of LCN2 expression in breast cancer. METHODS: The expression of LCN2 protein was immunohistochemically assessed in two well-characterised annotated cohorts of breast cancer (discovery cohort, n = 612; validation cohort, n = 1363). The relationship of LCN2 expression and subcellular location with the clinicopathological factors and outcomes of patients was analysed. RESULTS: Absent or reduced nuclear LCN2 expression was associated with features of aggressive behaviour, including high histological grade, high Nottingham Prognostic Index, high Ki67 labelling index, hormone receptor negativity and human epidermal growth factor receptor 2 positivity. The high cytoplasmic expression of LCN2 was correlated with lymph node positivity. The nuclear downregulation of LCN2 was correlated with the overexpression of EMT associated proteins (N-cadherin and Twist-related protein 2) and basal biomarkers (cytokeratin 5/6 and epidermal growth factor receptor). Unlike the cytoplasmic expression of LCN2, the loss of nuclear expression was a significant predictor of poor outcome. The combinatorial expression tumours with high cytoplasmic and low nuclear expression were associated with the worst prognosis. CONCLUSIONS: Tumour cell expression of LCN2 plays a role in breast cancer progression with loss of its nuclear expression which is associated with aggressive features and poor outcome. Further functional analysis is warranted to confirm the relationship between the subcellular localisation LCN2 and behaviour of breast cancer.

Synoptic Versus Narrative Reporting of Prostate Biopsies at a Tertiary Healthcare Institution: Challenges, successes and expectations.

OBJECTIVES: Cancer pathology reports are expected to contain all information required for patient management and disease surveillance. Moreover, reports for patients with prostate cancer have become increasingly complex with the addition of more pathological details. This study aimed to compare narrative and synoptic prostate cancer reports for core needle biopsies received at a tertiary hospital in Nigeria in order to determine which form was most complete according to international standards. METHODS: This study was conducted from January 2010 to December 2015 at the Lagos University Teaching Hospital, Lagos, Nigeria. All malignant prostate cancer histopathology reports received during this period were analysed for the presence of important clinicopathological parameters, including the numbers of cores taken and those involved by the tumour, percentage of tumour involvement, Gleason score and the presence of high-grade prostatic intraepithelial neoplasms (HGPINs) and perineural and lymphovascular invasion. RESULTS: A total of 83 reports were reviewed, of which 27 were in narrative and 56 in synoptic format. The documentation of clinicopathological characteristics in narrative reports was significantly incomplete compared to synoptic reports in recording the number of cores (33.3% versus 96.4%), number of cores involved by the tumour (11.1% versus 94.6%), percentage of cores involved by the tumour (3.7% versus 100.0%) and the presence of HGPINs (7.4% versus 100.0%) and perineural (59.3% versus 98.2%) and lymphovascular (48.1% versus 100.0%) invasion (P <0.001 each). CONCLUSION: Synoptic reports of malignant prostate cancer biopsies received at the Lagos University Teaching Hospital were found to contain more complete information than narrative reports.

Remote Teaching of Histopathology Using Scanned Slides via Skype Between the United Kingdom and Nigeria.

CONTEXT: -Web-based learning is a major component of distance education. OBJECTIVE: -To explore Web-based applications for pathology teaching in resource-limited sub-Saharan Africa. DESIGN: -The participants were consultant pathologists and trainees drawn from tertiary institutions in Nigeria. They viewed the digital slides via the Leeds virtual pathology Web site, after which, interactive lectures were given via Skype (Skype Communications, Luxembourg City, Luxembourg). Questionnaires were administered via SurveyMonkey (Palo Alto, California) to all participants of 12 sessions between 2014 and 2015. RESULTS: -Nine consultant pathologists and 33 trainees participated in this survey. Of all respondents, 29 (69%) thought it was fairly easy to navigate the system, 11 (26.2%) thought it was easy, whereas 2 (4.8%) felt it was difficult. In addition, 26 respondents (61.9%) found it fairly easy to make a make a diagnosis, 13 (31%) thought it was easy, and 3 (7.1%) noted that it was difficult. Twenty-four respondents (57.1%) had a fairly smooth user experience, 12 (28.6%) experienced occasional crashes, whereas 6 (14.3%) reported a smooth experience. Almost all (41 of 42; 97.6%) respondents felt the pathology teaching was beneficial to their local pathology practice, and all (100%) indicated the need for additional, similar sessions. CONCLUSION: -The beneficial applications of Internet-based lectures make them a viable, cheaper, and cost-effective alternative to face-to-face lectures in our environment.

Follicular lymphoma in situ presenting as dermatopathic lymphadenopathy.

Introduction. Follicular lymphoma in situ (FLIS) is a recently described entity with few cases recognized worldwide. To our knowledge, this is the first FLIS reported from West Africa. Case Presentation. We present the case of a 48-year-old civil servant with axillary lymphadenopathy discovered on routine mammography. On histology, a predominant reactive change with aggregates of melanophages was seen prompting a diagnosis of reactive lymphadenopathy. Immunohistochemistry done in our laboratory showed CD10 and Bcl-6 positive germinal centres with a small population of Bcl-2 positive germinal centre centre cells that were limited to some of the germinal centres. Conclusion. This highlights the use of immunohistochemistry in lymph node pathology-a resource which is very limited in our environment.