Background: Flat epithelial atypia (FEA) is defined as an intraductal proliferation of 3-5 layers of mildly atypical cells¹. It is classified as a B3 lesion on biopsy². Inter-observer variability in diagnosis exists and surgical/radiological management remains controversial due to lack of clarity on upgrade rates³ ⁴.
Purpose: To review all pure FEA lesions diagnosed on breast biopsy to identify upgrade rates and long-term outcomes.
Methods: 28,875 breast biopsy diagnoses were reviewed between 2010-2022. Cases of pure FEA in patients with no previous history of breast in situ or invasive carcinoma were re-reviewed by 2 specialised breast pathologists (PM, MVW; both members of UK NCCBP). Age of patient, imaging findings, excision findings, and long term radiological outcomes were recorded.
Results: 413 cases of FEA were diagnosed on biopsy in patients with no prior history of breast malignancy (1.4%). Of these, 195 (47.2%) were pure FEA without associated ADH, DCIS or in situ lobular neoplasia. Overall mean age at diagnosis: 51.9 years. Over 90% of these were associated with mammographic microcalcification; other imaging findings included textural changes or mass lesions. 74/195(37.9%) were managed by radiological follow up. Excision findings were: 56(28.7%) downgraded - benign; 55(28.2%) residual atypia; 10(5.13%) upgraded (3 IDC; 6 DCIS; 1 pleomorphic LCIS). 4/10 upgrades (40%) were associated with microcalcification only (size >9mm;/multifocality); 6/10 (60%) were associated with radiological textural changes/asymmetric density (ASD) +/- mass lesions/nipple discharge.
Conclusions: Pure FEA is a rare diagnosis (0.67%) on biopsy, of which 94.8% do not progress on surgical excision or radiological follow-up. Those that do progress are associated with radiological microcalcification size >9mm; multifocality; textural changes/ASD or clinical symptoms. We propose that all cases of pure FEA with microcalcification only and radiological/pathological concordance, lacking other clinical/radiological risk features should be managed conservatively.
 

Background: Altered cancer metabolism and genomic instability are two key cancer hallmarks. Cancer cells reprogram their metabolic pathways to meet their necessary energy and cellular block demands. Changes in DNA repair protein expression can cause genomic instability through increased DNA damage caused by endogenous and exogenous factors, such as reactive oxygen species. An association between the glutamine metabolism protein solute carrier family 7 member 5 (SLC7A5) and the DNA repair protein flap structure-specific endonuclease (FEN1) was previously investigated in a large series of breast cancer (BC) using immunohistochemistry.

Purpose: This study aims to explore the potential association between glutamine metabolism and DNA repair in BC using in vitro models.

Methods: Western blot was used to assess SLC7A5 and FEN1 protein in BC cell lines previously transfected via siRNA to knockdown either SLC7A5 or FEN1. Co-immunoprecipitation (Co-IP) was used to investigate the protein-protein interactions involved between SLC7A5 and FEN1.

Results: SLC7A5 protein was decreased in BC cell lines with FEN1 knockdown and similarly FEN1 was decreased with SLC7A5 knockdown (p<0.05), as this was seen in both luminal A cell line MCF-7 and triple-negative cell line MDA-MB-436. using Co-IP and mass spectrometry co-partners were determined between SLC7A5 and FEN1 in both MCF-7 and MDA-MB-436 cell lines.

Conclusion: This study provides evidence that shows by investigating the relation between SLC7A5 and FEN1 there is an association between glutamine metabolism and DNA repair in BC which could have therapeutic implications.

Keywords: breast cancer, glutamine metabolism, DNA repair, SLC7A5, FEN1
 

The contribution of co-localisation of Solute Carriers in Breast Cancer
Busra Erkan1, Ali Fakroun1, Ian O Ellis1, Emad A Rakha1, Andrew R Green1
1Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham
Background:
Breast cancer (BC) is a heterogeneous disease with a wide range of clinical outcomes. Glutamine is a key nutrient for tumour growth and progression in several BC subtypes. The expression of solute carriers associated with glutamine: SLC1A5, SLC3A2, and SLC7A5, in BC has been shown to predict poor prognosis.
Purpose:
To confirm the co-localisation and intra-tumoural heterogeneity of SLC1A5, SLC3A2, and SLC7A5 expression in BC, while also investigating their relationships with clinicopathological parameters.
Methods:
Multiplex immunohistochemistry (mIHC) was utilised to determine co-expression of SLC1A5, SLC3A2, and SLC7A5 in full-face BC sections (n=30). Homogeneity of SLC expression was assessed by analysing slides scanned at 40x magnification using the Nano-Zoomer Digital Scanner and subjected to quantitative digital image analysis employing Qu-Path version 0.5.0, an open-source digital pathology software. The annotations were generated to delineate regions of interest, facilitating the quantification of co-expression and spatial distribution. These findings were correlated with clinicopathological parameters.
Results:
In the invasive BC cells, there were variations in the homogenous staining of SLC1A5/SLC7A5 and SLC7A5/SLC3A2 ranging from 3.7-59.8%. The staining revealed areas of no expression, single expression, and dual expression. There were no regions showing co-expression of SLC1A5/SLC3A2. The co-expression of SLCs were associated with larger tumour size, poor NPI, age and TNBC.
Conclusion:
The co-expression of SLCs in BC correlates with some aggressive tumour features. This suggests their spatial distribution and co-expression potential role as indicators of tumour aggressiveness and may warrant further investigation as potential therapeutic targets.
 

Background: Encapsulated papillary carcinoma (EPC) of the breast is a rare form of breast carcinoma, comprising only 0.5%-1% of all breast cancers (Tan et al., 2023). Its lack of a distinct myoepithelial cell layer surrounding the lesion has caused speculation about its invasive nature.

Purpose: To retrospectively investigate whether variables such as patient age and tumour characteristics have effects on EPC invasion.

Methods: 35 patient cases of EPC from Lincoln County Hospital were examined, retrospectively, reviewing data from January 2019 to December 2022. Basic demographic data was collected and examined using Microsoft Excel version 16.79.2. For statistical analysis, SPSS Version 29.0.1.0 was used, employing Descriptive statistics, Spearmen’s Rank Correlation Coefficient, and an independent samples T-test. These aided in investigating associations between whole tumour size (WTS), patient age and invasive tumour components.

Results: Of the 35 cases the median tumour size was 18mm with an interquartile range of 19mm. One focally invasive case was identified, however, 42.86% (n=15) presented alongside an adjacent invasive carcinoma. Those with an associated invasive carcinoma had a significantly larger WTS in comparison to pure EPC (p=0.003). There was no statistically significant association between WTS and patient age (p=0.388) or size of invasive components (p=0.861).

Conclusions: EPC is an indolent neoplasm that often culminates in good clinical prognosis. Despite its architectural similarities to more invasive carcinomas, its biological behaviour aligns with in situ breast tumours. Clinical management should remain in line with current guidance. More comprehensive classification may enhance surveillance and understanding of rarer subtypes, necessitating respect for these lesions to be recognised as a distinct entity with specific subclassification. While no statistically significant associations have been identified regarding tumour behaviour, oestrogen receptor positivity is thought to play a role. Further research is required to confirm this.
 

Background:
Ovarian cancer is a leading cause of death in gynaecological cancers . Evidence suggests that complete macroscopic resection of cancer, or as close to as possible, confers a survival benefit. However, the intraoperative assessment of residual cancer volume is subjective as there is no existing objective tool for this assessment.

Purpose:
In this work we evaluate the viability of Raman spectroscopy for assessment of ovarian cancer and thus, consideration as the answer to this important clinical need.

Methods:
Raman spectroscopy measurements were taken from ex vivo ovarian and peritoneal tissue from seventy-three participants (n=20 benign, n=11 borderline and n=42 cancer). The spectra were analysed using a multivariate analysis model and compared to histology of consecutive frozen sections from the same tissue block. Classification and leave one out cross validation performance were recorded.

Result:
In ovarian tissue this model achieved 94% sensitivity and 98% specificity for prediction of cancer from benign (AUC 0.97) and 98% sensitivity and 89% specificity for prediction of cancer from borderline (AUC 0.99). In peritoneal tissue, the model achieved 78% sensitivity and 84% specificity for prediction of cancer from benign in participants who had primary surgery (AUC 0.86) and 68% sensitivity and 81% specificity in participant who had post chemotherapy surgery (AUC 0.79).

Conclusions
It is unclear whether the difference in the primary and post chemotherapy group performance infers an effect of chemotherapy, and this needs further study. Raman spectroscopy was able to classify cancer from non-cancer with high cross-validation accuracies and to our knowledge, this is the first time borderline ovarian tumours have been assessed using Raman spectroscopy.
Raman spectroscopy is a viable technique for the assessment of ovarian cancer.
 

Background and purpose:
Placental pathology comprises a substantial portion of histopathology workload in the UK. Due to increasing accessions and limited consultant reporting time, our department implemented the Royal College of Pathologists' placental tissue pathway for selective examination. This study evaluates the impact of this approach in a District General Hospital in Essex, UK.

Methods:
We audited placenta specimens received in 2020 and retrospectively assessed their triage status using RCPath guidelines. Implementation occurred in January 2023 to streamline reporting and processing time. We analyzed the workload, including consultant reporting time, registrar bench time, and laboratory processing time, as well as cost implications.

Results:
Results showed a 200% increase in placenta specimens from 2019 to 2020. Applying RCPath guidelines in 2020 would have reduced the number of specimens requiring full examination by over half. From January 2023 to February 2024, 332 placentas were received, with 104 not examined, 79 macroscopically examined only, and 149 fully examined including histology. Turnaround time for fully examined placentas decreased from 42 to 12 days, with 90% reported within 12 days. Placentas not examined or macroscopically examined had a report turnaround time of 8 days on average. No clinical requests were made for further examination of triaged placentas during the audited period.

Conclusion:
In conclusion, implementing RCPath guidelines effectively rationalized reporting and processing time for placental pathology, resulting in cost savings and improved efficiency in our department.