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result(s) for
"Schmolze, Dan"
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Building pathology capacity in sub-Saharan Africa to improve breast cancer diagnosis and treatment: training laboratory technicians in high-quality manual immunohistochemistry
by
Setiawan, Linda
,
Graef, Katy
,
Schmolze, Dan
in
Africa South of the Sahara
,
Automation
,
Biomarkers
2024
Background
To address the need for a skilled workforce in breast cancer (BC) pathology in sub-Saharan Africa (SSA), we implemented an education program to train laboratory technicians in manual immunohistochemistry (IHC).
Methods
A quality improvement education project was developed. Interactive webinars were held every six months with didactics and presentations from African experts with experience in IHC. We conducted knowledge assessments and surveys on current practice, equipment, and human resources. A digital mentorship platform (DMP) was created for discussions, sharing SOPs, and networking. For one year (2022–2023), we followed developments in pathology capacity, practice changes, and educational needs. A paired t-test was used to calculate the significance of changes in knowledge immediately after the webinar and comfort level with topics 35 days after the webinar.
Results
Two hundred and sixty six participants from 10 SSA countries attended the first webinar, a series of six lectures on IHC theory, methods, and practice. Ninety-five participants from nine SSA countries provided a baseline assessment of pathology capacity and feedback. Mean knowledge increased by 17.4% immediately after the webinar (from 41.8% pre-webinar to 59.2% post,
p
= < 0.0001). Self-reported comfort level in topics 35 days after the webinar increased by 11.3%, but this was not statistically significant (mean 3.36 pre- to 3.74 post,
p
= 0.1). Over six months, recordings were accessed 412 times. After six months, the second webinar had 93 participants from eight SSA countries. Membership in the DMP increased from 64 to 172; recordings were viewed 412 times in six months; and 113 participants from nine SSA countries completed surveys. Among 74 respondents who perform IHC, 43.5% reported moderate or significant positive practice changes such as improved antigen retrieval techniques and optimization of preanalytical variables. Over half (52.7%,
n
= 39) reported the quality of slides had moderately or significantly improved. After one year, a third webinar had 98 participants from eight SSA countries. Thirty-eight completed surveys, DMP membership increased to 199, and 1 reported launching IHC in a lab in Nigeria.
Conclusions
Our program 1) reached hundreds of participants and provided a baseline assessment of pathology capacity across nine SSA countries; 2) created a novel mechanism to build pathology capacity and assess progress with this cohort; and 3) improved practices and the preparation of slides for over half performing manual IHC. After one year, interest was sustained. Tracking impact on diagnosis and treatment of BC in the region is needed long-term.
Journal Article
Gene expression associated with endocrine therapy resistance in estrogen receptor-positive breast cancer
2025
Despite endocrine therapy (ET), approximately 20–40% of Stage I–III estrogen receptor-positive breast cancer (ER + BC) patients experience recurrence. Recurrence while on ET is indicative of ET resistance. This study aimed to identify differentially expressed genes (DEGs) associated with recurrence during ET (ET resistance) and to explore gene expression differences across PAM50 molecular subtypes. Eighty tumor specimens from 79 patients treated at the City of Hope Comprehensive Cancer Center (2012–2016) were analyzed using NanoString technology. Fourteen patients (17.7%) experienced recurrence over a median follow-up of 68 months (range 35–104 months). Key upregulated DEGs in the recurrence group included
EZH2
(log2 fold change[log2FC]: 0.67,
p
= 0.0017),
WNT11
(log2FC: 1.08,
p
= 0.0088),
ITGB6
(log2FC: 0.80,
p
= 0.0312), and
TOP2A
(log2FC: 0.79,
p
= 0.0381). Downregulated DEGs included
SNAI2
(log2FC: − 0.63,
p
= 0.0055),
ITPR1
(log2FC: − 0.75,
p
= 0.0083),
CD10
(log2FC: − 0.70,
p
= 0.0092),
PTEN
(log2FC: − 0.29,
p
= 0.0163),
VRD
(log2FC: − 0.46,
p
= 0.0184), and
WNT5A
(log2FC: − 0.76,
p
= 0.0272).
EZH2
and
TOP2A
were positively correlated with proliferation scores, while
WNT11
and
ITGB6
emerged as potential biomarkers independently associated with recurrence. These findings suggest novel biomarker candidates that could help overcome ET resistance, reduce recurrence, and improve outcomes in ER + BC.
Journal Article