[Implementation of the Bethesda system for reporting the thyroid cytopathology: study on 5 729 cases from a cancer center].

Objective: To analyze the data of the Bethesda system for reporting thyroid cytopathology applied in a comprehensive cancer center and to evaluate the diagnostic ability of fine needle aspiration (FNA). Methods: We retrospectively reviewed the medical records of 5 729 cases applying this reporting system at Cancer Hospital, Chinese Academy of Medical Sciences. The series were from 5 011 patients including 1 174 men and 3 837 women, and their median age was 45 years (range, 7-88 years). FNA results were correlated with final histological diagnosis after surgery and the accuracy of FNA diagnosis and the malignancy rates for each of categories were also analyzed. Results: Among 5 729 thyroid aspirates, aside from 456 (8.0%) cases with nondiagnostic or unsatisfactory (ND/UNS) outcomes, 1 055 (18.4%) cases were benign, 409 (7.1%) cases showed atypical of undetermined significance or follicular lesions with undetermined significance (AUS/FLUS), 80 (1.4%) cases were follicular neoplasm or suspicious for follicular neoplasm (FN/SFN), 982 (17.1%) cases were suspicious for malignancy (SUS), and 2 747 cases were malignant (47.9%). Of 5 729 cases, 3 239 had received thyroidectomies after FNA, 95.99% of them were proven histologically to be malignant, with following malignancy rates in individual FNA categories: ND/UNS 75.00%; benign 40.91%; AUS/FLUS 77.67%; FN/SFN 41.67%; SUS 96.86%; and malignant 99.96%. FNA predicted malignancy with sensitivity, specificity, accuracy, positive predictive value and negative predictive values of 98.8%, 60.5%, 97.7%, 98.9% and 59.1%, respectively. Conclusions: The data of the Bethesda reporting system indicates high proportion of malignant diagnosis and high risk of malignancy at all FNA diagnostic categories. FNA offers high diagnostic accuracy and positive predictive value for the diagnosis of thyroid diseases.

A novel calmodulin-regulated Ca2+-ATPase (ACA2) from Arabidopsis with an N-terminal autoinhibitory domain.

To study transporters involved in regulating intracellular Ca2+, we isolated a full-length cDNA encoding a Ca2+-ATPase from a model plant, Arabidopsis, and named it ACA2 (Arabidopsis Ca2+-ATPase, isoform 2). ACA2p is most similar to a "plasma membrane-type" Ca2+-ATPase, but is smaller (110 kDa), contains a unique N-terminal domain, and is missing a long C-terminal calmodulin-binding regulatory domain. In addition, ACA2p is localized to an endomembrane system and not the plasma membrane, as shown by aqueous-two phase fractionation of microsomal membranes. ACA2p was expressed in yeast as both a full-length protein (ACA2-1p) and an N-terminal truncation mutant (ACA2-2p; Delta residues 2-80). Only the truncation mutant restored the growth on Ca2+-depleted medium of a yeast mutant defective in both endogenous Ca2+ pumps, PMR1 and PMC1. Although basal Ca2+-ATPase activity of the full-length protein was low, it was stimulated 5-fold by calmodulin (50% activation around 30 nM). In contrast, the truncated pump was fully active and insensitive to calmodulin. A calmodulin-binding sequence was identified within the first 36 residues of the N-terminal domain, as shown by calmodulin gel overlays on fusion proteins. Thus, ACA2 encodes a novel calmodulin-regulated Ca2+-ATPase distinguished by a unique N-terminal regulatory domain and a non-plasma membrane localization.