Publications

@article{Sculthorpe2025-jm,

title = {High α-SMA expression in the tumor stroma is associated  with adverse clinical parameters in mismatch repair-proficient  colorectal cancers only},

author = {Declan J Sculthorpe and Amy Denton and Wakkas Fadhil and Dewi Rusnita and Mohammad Ilyas and Abhik Mukherjee},

doi = {10.1093/ajcp/aqae145},

year  = {2025},

date = {2025-03-01},

urldate = {2025-03-01},

journal = {Am. J. Clin. Pathol.},

volume = {163},

number = {3},

pages = {464\textendash472},

publisher = {Oxford University Press (OUP)},

abstract = {OBJECTIVES: As mismatch repair status confers differential 

 prognosis in colorectal cancers, this study aimed to determine 

 associations of α-smooth muscle actin (α-SMA) 

 protein expression in mismatch repair-proficient (pMMR) and 

 mismatch repair-deficient (dMMR) colorectal tumors with 

 clinicopathologic and prognostic features. METHODS: Tissue 

 microarrays from patients with colorectal cancer, immunostained 

 with α-SMA, were assessed through digital image analysis. Total (n = 962), pMMR (n = 782), and dMMR (n = 156) stromal 

 H-scores were assessed for associations with clinicopathologic 

 and survival data. RESULTS: Higher α-SMA expression was correlated with pMMR status (P = 5.2223 $times$ 10-8). In the 

 pMMR subgroup, higher α-SMA stromal expression at the tumor periphery was correlated with higher T stage (P = .002), perineural invasion (P = .038), infiltrative tumor edge (P = .01), involved nodal status (P = .036), metastases (P = .013), synchronous metastases (P = .007), recurrence (P = .004), and both 3-year and 5-year survival (P = .018). dMMR tumors showed 

 no significant correlations with α-SMA staining. 

 CONCLUSIONS: The findings highlight that immunostaining with 

 α-SMA in pMMR colorectal tumors, especially at the tumor 

 periphery, has the potential to identify patients with adverse 

 prognostic features. Digital assessment of α-SMA may 

 offer improved objectivity, accuracy, economy of time, and risk 

 stratification for management.},

keywords = {biomarker analysis, colorectal cancer, digital image analysis, DNA mismatch repair, immunohistochemistry, α-SMA},

pubstate = {published},

tppubtype = {article}

}

@article{Sculthorpe2024-ie,

title = {Advantages of automated immunostain analyses for complex  membranous immunostains: An exemplar investigating loss of  E-cadherin expression in colorectal cancer},

author = {Declan Sculthorpe and Amy Denton and Dewi Rusnita and Wakkas Fadhil and Mohammad Ilyas and Abhik Mukherjee},

doi = {10.1016/j.prp.2024.155470},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Pathol. Res. Pract.},

volume = {260},

number = {155470},

pages = {155470},

publisher = {Elsevier BV},

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.},

keywords = {biomarker analysis, colorectal cancer, Digital pathology, Image   analysis, immunohistochemistry},

pubstate = {published},

tppubtype = {article}

}