Comparison of Cytoplasmic and Nuclear MTAP Loss in Pleural Effusion Cytology: Correlation With Homozygous p16/ CDKN2A Deletion

OpenAlex İngilizce

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.