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Published on: November 5, 2019
Comparison of Cytoplasmic and Nuclear MTAP Loss in Pleural Effusion Cytology: Correlation With Homozygous p16/CDKN2A
Nazli Sena Şeker1, Emel Yaldir1, Osman Furkan Mulkem1
1Department of Medical Pathology, Eskişehir Osmangazi University Faculty of Medicine, Meşelik, Turkey.
Objective:
Pleural mesothelioma (PM) is an aggressive malignancy in which pleural effusion cytology is often the first diagnostic material. MTAP immunohistochemistry, while not a stand-alone diagnostic tool, may serve as a useful adjunct when combined with other markers in the evaluation of pleural mesothelioma. However, the diagnostic relevance of nuclear versus cytoplasmic MTAP loss in cytology specimens remains unclear.
Methods:
We retrospectively analysed pleural effusion cytology samples from 48 histologically confirmed PM cases (2017-2022). Dual-colour fluorescence in situ hybridization (FISH) was performed for p16/CDKN2A, while MTAP immunohistochemistry (Proteintech 2B1G6 clone) was assessed for nuclear and cytoplasmic loss, further subclassified as focal or diffuse. Associations between MTAP loss and p16/CDKN2A deletion were evaluated using Fisher's exact test.
Results:
MTAP loss was observed in 21 cases (43.8%), while homozygous p16/CDKN2A deletion was detected in 33 cases (68.8%). Concurrent MTAP loss and p16/CDKN2A deletion occurred in 15 cases (31.3%). Nuclear and cytoplasmic MTAP loss were perfectly concordant in terms of presence (p < 0.001), although their staining patterns differed: diffuse nuclear loss often corresponded to focal rather than diffuse cytoplasmic loss. No significant association was observed between MTAP staining patterns and p16/CDKN2A deletion (p > 0.05).
Conclusions:
Our findings demonstrate that while nuclear and cytoplasmic MTAP loss are concordant in presence, staining patterns and antibody clone selection affect correlation with p16/CDKN2A deletion. Given that pleural effusion cytology is often the initial diagnostic step in PM, standardised MTAP testing protocols are needed to ensure reproducibility and minimise false-negative interpretations, rather than implying improved diagnostic accuracy.
Insights
Methylthioadenosine phosphorylase (MTAP) loss in pleural mesothelioma cytology is concordant between nuclear and cytoplasmic staining. However, staining patterns and antibody selection impact correlation with p16/CDKN2A deletion, necessitating standardized protocols.
Area of Science:
- Oncology
- Cytopathology
- Molecular Pathology
Background:
- Pleural mesothelioma (PM) is an aggressive cancer often initially diagnosed via pleural effusion cytology.
- Immunohistochemistry for MTAP (methylthioadenosine phosphorylase) can aid PM diagnosis but its utility, particularly nuclear vs. cytoplasmic loss, requires clarification.
- Understanding MTAP loss patterns is crucial for refining diagnostic adjuncts in PM evaluation.
Purpose of the Study:
- To investigate the diagnostic relevance of nuclear versus cytoplasmic MTAP loss in pleural mesothelioma cytology specimens.
- To assess the concordance between MTAP loss and p16/CDKN2A deletion in PM.
- To evaluate the impact of staining patterns and antibody clone on MTAP assessment.
Main Methods:
- Retrospective analysis of 48 histologically confirmed PM pleural effusion cytology samples.
- Dual-color fluorescence in situ hybridization (FISH) for p16/CDKN2A.
- MTAP immunohistochemistry assessed for nuclear and cytoplasmic loss (focal/diffuse).
Main Results:
- MTAP loss observed in 43.8% of cases; homozygous p16/CDKN2A deletion in 68.8%.
- Nuclear and cytoplasmic MTAP loss were concordant in presence (p < 0.001).
- No significant association found between MTAP staining patterns and p16/CDKN2A deletion (p > 0.05).
Conclusions:
- Nuclear and cytoplasmic MTAP loss are concordant but staining patterns affect correlation with p16/CDKN2A deletion.
- Standardized MTAP testing protocols are essential for reproducible results in pleural effusion cytology.
- Refined protocols can minimize false-negative interpretations in PM diagnosis.
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