CK19 Expression in ACTH-Producing Extrapituitary Neuroendocrine Neoplasms is a Negative Prognostic Factor.

Introduction: Defining localization and potential ACTH-producing extrapituitary neuroendocrine neoplasms (ACTH-epNEN) is important for clinical practice. Aim(s): To assess CK19 expression in ACTH-epNEN of different localization. Materials and methods: CK19 (clone RCK108) and Ki-67 (clone MIB-1) expression were evaluated immunohistochemically (IHC) in 37 ACTH-epNEN specimens: 19 lung (L-NEN) (51.3%); eight thymus (T-NEN) and two mediastinal (M-NEN) (27.2%); six gastrointestinal (GI): three pancreatic (Pn-NEN), one ampulla Vater's (AV-NEN), one appendical (A-NEN), one rectal (R-NEN) (16.2%); two medullary thyroid carcinomas (MTC) (5.4%); in 13 men and 25 women, at mean age 42.1 (16-67 yrs). Results: Clinical presentation of ACTH-ectopic syndrome was diagnosed in 30 (81.1%) patients (pts) at early stage, in three (8.1%) pts at late stage of the disease (Pn-NEN, AV-NEN, R-NEN). Four tumors (10.8%) were asymptomatic (2 L-NEN, Pn-NEN, M-NEN). Twenty of 37 (54.1%) ACTH-epNEN had CK19 expression: in 9/10 T-NEN and M-NEN (90%), 2/2 MTC (100%), 4/6 GI-NEN (66.7%) and 5/19 L-NEN (26.3%). All CK 19-positive ACTH-epNENs of GI and thyroid, mediastinum, thymus and three tumors of the lung were malignant (with metastases or recurrences). We got a strong correlation between CK19 expression in ACTH-epNE and an increased level of Ki-67 (Spearman r=0,75, p<0.001). Conclusion: CK19 expression in ACTH-epNEN is an important criteria for malignancy potential. Especially for L-NEN, this can be used to predict recurrence and metastases. [ABSTRACT FROM AUTHOR]