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TROP2 immunoreactivity in pulmonary large cell neuroendocrine carcinoma
Michael Minkley1, Kashif Ravasia2, Thi Nghiem3
1Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Introduction:
TROP2 antibody-drug conjugates have shown promising anti-tumour activity, but neither the activity of these agents nor TROP2 expression has been well studied in pulmonary large cell neuroendocrine carcinoma (LCNEC), a rare and aggressive cancer type. We aimed to (i) determine the prevalence of TROP2 immunoreactivity in LCNEC; (ii) assess whether TROP2 immunoreactivity in LCNEC is related to RB1 loss on IHC or to the presence of NSCLC or SCLC components and (iii) determine whether TROP2 immunoreactivity in LCNEC has prognostic significance.
Methods:
TROP2 immunohistochemistry was performed on 58 pure LCNECs and 25 areas of LCNEC that were combined with other carcinomas, in tissue microarray format. TROP2 was scored for the percent of tumour cells staining, and with evaluation of cytoplasmic versus membranous staining, approximating a previously published predictive scoring method.
Results:
TROP2 staining in ≥1% and ≥50% of LCNEC cells was present in 60% and 26% of pure LCNEC tumours, respectively. Cytoplasmic-type staining, previously implicated in greater antibody-drug conjugate response, was present in 48% of pure LCNEC cases. Positive TROP2 staining was less frequent in pure LCNEC than in the LCNEC component of tumours that also contained a NSCLC component (≥1%: P = 0.0087; ≥50%: P = 0.011), and ≥50% TROP2 staining in pure LCNEC was associated with retained RB1 staining on immunohistochemistry (P = 0.032). TROP2 staining was not associated with recurrence-free survival or disease-specific survival outcomes.
Conclusion:
Frequently positive TROP2 IHC suggests that TROP2 antibody-drug conjugates may be potential treatments for LCNEC.
Insights
TROP2 expression is common in large cell neuroendocrine carcinoma (LCNEC), suggesting TROP2 antibody-drug conjugates could be a potential treatment for this rare cancer. Further research is needed to confirm efficacy.
Area of Science:
- Oncology
- Translational Research
Background:
- Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive cancer.
- TROP2 expression and the efficacy of TROP2 antibody-drug conjugates are not well-established in LCNEC.
Purpose of the Study:
- Determine TROP2 expression prevalence in LCNEC.
- Investigate the relationship between TROP2 expression, RB1 loss, and mixed NSCLC/SCLC components.
- Assess the prognostic significance of TROP2 expression in LCNEC.
Main Methods:
- TROP2 immunohistochemistry (IHC) performed on 58 pure LCNECs and 25 mixed LCNEC cases.
- Scored TROP2 for percentage of positive tumor cells and staining pattern (cytoplasmic vs. membranous).
- Correlated TROP2 expression with RB1 loss and clinical outcomes.
Main Results:
- TROP2 staining in ≥1% and ≥50% of tumor cells observed in 60% and 26% of pure LCNEC, respectively.
- Cytoplasmic TROP2 staining, linked to better ADC response, found in 48% of pure LCNEC.
- Positive TROP2 staining was less frequent in pure LCNEC compared to LCNEC with NSCLC components.
- ≥50% TROP2 staining in pure LCNEC was associated with retained RB1 expression.
- TROP2 expression did not correlate with recurrence-free or disease-specific survival.
Conclusions:
- Frequent TROP2 expression in LCNEC indicates potential for TROP2 antibody-drug conjugate therapy.
- TROP2 IHC is a valuable tool for assessing treatment potential in LCNEC.
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