BackgroundWell-differentiated neuroendocrine tumors (NET) most frequently arise from the gastrointestinal tract (GI), pancreas, and lung. Patients often present as metastasis with an unknown primary, and the clinical management and outcome depend on multiple factors, including the accurate diagnosis with the tumor primary site. Determining the site of the NET with unknown primary remains challenging. Many biomarkers have been investigated in primary NETs and metastatic NETs, with heterogeneous sensitivity and specificity observed.MethodsWe used high-throughput tissue microarray (TMA) and immunohistochemistry (IHC) with antibodies against a panel of transcriptional factors including NKX2.2, PDX-1, PTF1A, and CDX-2 on archived formalin-fixed paraffin-embedded NETs, and investigated the protein expression pattern of these transcription factors in 109 primary GI (N = 81), pancreatic (N = 17), and lung (N = 11) NETs.ResultsDifferential expression pattern of these markers was observed. In the GI and pancreatic NETs (N = 98), NKX2.2, PDX-1, and CDX-2 were immunoreactive in 82 (84%), 14 (14%), and 52 (52%) cases, respectively. PDX-1 was expressed mainly in the small intestinal and appendiceal NETs, occasionally in the pancreatic NETs, and not in the colorectal NETs. All three biomarkers including NKX2.2, PDX-1, and CDX-2 were completely negative in lung NETs. PTF1A was expressed in all normal and neuroendocrine tumor cells.ConclusionsOur findings suggest that NKX2.2 was a sensitive and specific biomarker for the GI and pancreatic neuroendocrine tumors. We proposed that a panel of immunostains including NKX2.2, PDX-1, and CDX-2 may show diagnostic utility for the most common NETs.
Background Determining human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma can have a significant impact on treatment and clinical outcomes. Because fine‐needle aspiration (FNA) is typically an initial diagnostic modality in a patient workup for primary or suspected metastatic disease, immunostaining for p16 on FNA material is a promising option to determine HPV tumor status, possibly avoiding biopsies or excisions. In this study, the authors investigated the possibility of using alcohol‐fixed smears as a reliable alternative for reporting p16 status. Methods Twenty HPV‐associated tumors and 20 non‐HPV–associated tumors were identified using the gold‐standard histologic cutoff for positivity of ≥70% strong nuclear and cytoplasmic staining. Matched FNA specimens were identified for comparison staining, and a positive p16 result was rendered on a single aspirate smear using the same cutoff of ≥70%. Results On alcohol‐fixed cytology smears, 16 of 20 (80%) HPV‐associated tumors showed positive p16 staining in ≥70% tumor cells. Four cases showed lower level (30%‐60%) nuclear and cytoplasmic staining. Nineteen of 20 (95%) non‐HPV–associated tumors showed no or minimal p16 staining (0%‐10%), and 1 case had a p16‐equivocal cytology result. Conclusions The authors performed immunocytochemical validation for p16 using alcohol‐fixed smears and observed promising results, offering this technique as a potential alternative to formalin‐fixed tissue in the appropriate clinical context. By using a positive staining cutoff of ≥70%, this technique offers 80% sensitivity and 95% specificity for detecting HPV‐associated tumors. Although it was not performed in the current study, HPV‐specific testing on available formalin‐fixed, paraffin‐embedded tissue should be considered in cases with equivocal or negative p16 staining.
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