ABSTRACT
As pathology moves towards digitisation, biomarker profiling through automated image analysis provides potentially objective and time-efficient means of assessment. This study set out to determine how a complex membranous immunostain, E-cadherin, assessed using an automated digital platform fares in comparison to manual evaluation in terms of clinical correlations and prognostication. Tissue microarrays containing 1000 colorectal cancer samples, stained with clinical E-cadherin antibodies were assessed through both manual scoring and automated image analysis. Both manual and automated scores were correlated to clinicopathological and survival data. E-cadherin data generated through digital image analysis was superior to manual evaluation when investigating for clinicopathological correlations in colorectal cancer. Loss of membranous E-cadherin, assessed on automated platforms, correlated with: right sided tumours (p = <0.001), higher T-stage (p = <0.001), higher grade (p = <0.001), N2 nodal stage (p = <0.001), intramural lymphovascular invasion (p = 0.006), perineural invasion (p = 0.028), infiltrative tumour edge (p = 0.001) high tumour budding score (p = 0.038), distant metastasis (p = 0.035), and poorer 5-year (p= 0.042) survival status. Manual assessment was only correlated with higher grade tumours, though other correlations become apparent only when assessed for morphological expression pattern (circumferential, basolateral, parallel) irrespective of intensity. Digital assessment of E-cadherin is effective for prognostication of colorectal cancer and may potentially offer benefits of improved objectivity, accuracy, and economy of time. Incorporating tools to assess patterns of staining may further improve such digital assessment in the future.
ABSTRACT
PURPOSE: This study investigates natrium iodide symporter (NIS) expression in three breast cancer subtypes to predict radioiodine response. MATERIALS AND METHODS: Frozen breast tissues from triple negative (TN), human epidermal receptor 2 (HER2+), and luminal A cancers were used in this research. NIS protein expression in each subtype was analyzed using immunohistochemistry (IHC) and western blot (WB). Secondary data such as age, subtypes, and Ki 67 index were drawn from the surgical oncologist database. Breast cancer cell lines were used to investigate the effect of radioiodine by measuring cell proliferation. RESULTS: The forty-one breast cancer samples were analyzed consisted of the following subtypes: TN, HER2+, and luminal A were 58%, 22%, and 20% respectively. The stages of disease were 2A to 4A. Most of samples were at 3B. Ki 67 index of TN, HER2+, and luminal A were 21 ± 12, 19 ± 5, and 7 ± 3 respectively. The NIS expression was detected in 95% of samples in cytoplasm and/or cell membrane; 93% of samples were invasive breast carcinomas. Only 20% of the samples showed NIS expression at cell membrane; four samples were HER2+, and other four were TN subtypes. NIS membrane score was significantly positively correlated with Ki67 index, p = 0.04. NIS protein expression was detected at sizes 88 kDa, 50 kDa, and 27 kDa. Cell proliferation rate means of MDA-MB 231, SKBR3, and MCF7 cells were 81.6 ± 4, 10.6 ± 5, and 15.4 ± 13 respectively (p = 0.009). CONCLUSION: NIS protein expression is detectable in breast cancer cells to varying degrees. HER2+ is the most likely to express NIS in the cell membrane followed by TN subtypes. This indicates that radioiodine could be used as a novel adjuvant treatment in breast cancer.
