BACKGROUND: To date, thyroid fine‐needle aspiration (FNA) has been used by clinicians as the screening test of choice to determine whether surgery is required and this is what the pathology report should communicate. Standard terminology for reporting thyroid FNA has not been implemented yet, and pathologists have used various reporting systems to communicate results. A significant source of confusion among both pathologists and clinicians has been the use of the indeterminate category. On the basis of an analysis of 1150 thyroid FNAs in 2000, this institution modified the reporting of thyroid biopsy results into 6 categories, including unsatisfactory. The indeterminate category was separated into 3 subroups: 1) indeterminate for neoplasia (IND), 2) follicular neoplasm (FN), and 3) suspicious for malignancy (SUSP). Repeat FNA in 6 months to 12 months was recommended for IND and surgery for FN and SUSP categories. METHODS: To determine the validity of this approach, the outcomes of this reporting system from July of 2000 to December of 2006 were analyzed. The IND category was used for 2 subsets of cases: (a) those that morphologically fall into the gray zone between adenomatoid nodule (AN) and FN, for Hurthle cell nodule (hyperplasia vs neoplasm), and chronic lymphocytic thyroiditis with concern for neoplasia; and (b) for suboptimal specimens due to low epithelial cellularity or collection artifacts. RESULTS: Among 5194 thyroid nodules, the IND category comprised 18%. FNA follow‐up was done in 21% of IND cases: 58% were benign/negative and did not require surgery based on cytology alone. Surgical follow‐up in 46% of IND showed 52% were benign/negative, and 42% were follicular/Hurthle cell adenomas. The surgical yield of malignancy in IND was low (6%) when compared with the FN category, which was 14% (more than 2× that of the IND category), and the SUSP category, which was 53% (almost 9× that of the IND category). CONCLUSIONS: A 6‐tier reporting system for thyroid FNA was effective for determining which patients needed surgery versus follow‐up FNA and also guided the clinician on the extent of surgery. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.

MTA1 pro-angiogenic and pro-invasive functions create permissive environment for PCa tumor growth and likely support metastasis. Taken together with its predictive values, MTA1 can be utilized both as a prognostic marker and a therapy target in PCa.

Angiogenic switch in renal cell carcinoma (RCC) is attributed to the inactivation of the von Hippel-Lindau tumor suppressor, stabilization of hypoxia inducible factor-1 transcription factor and increased vascular endothelial growth factor. To evaluate the role of an angiogenesis inhibitor, thrombopsondin-1 (TSP1), we compared TSP1 production in human RCC and normal tissue and secretion by the normal renal epithelium (human normal kidney, HNK) and RCC cells. Normal and RCC tissues stained positive for TSP1, and the levels of TSP1 mRNA and total protein were similar in RCC and HNK cells. However, HNK cells secreted high TSP1, which rendered them nonangiogenic, whereas RCC cells secreted little TSP1 and were angiogenic. Western blot and immunostaining revealed TSP1 in the cytoplasm of RCC cells on serum withdrawal, whereas, in HNK cells, it was rapidly exported. Seeking mechanisms of defective TSP1 secretion, we discovered impaired calcium uptake by RCC in response to vascular endothelial growth factor. In HNK cells, 1,2-bis(o-aminophenoxy)ethane-N,N,N¢,N¢-tetraacetic acid acetoxymethyl ester, a calcium chelator, simulated TSP1 retention, mimicking the RCC phenotype. Further analysis revealed a profound decrease in transient receptor potential canonical ion channel 4 (TRPC4) Ca 2+ channel expression in RCC cells. TRPC4 silencing in HNK cells caused TSP1 retention and impaired secretion. Double labeling of the secretory system components revealed TSP1 colocalization with coatomer protein II (COPII) anterograde vesicles in HNK cells. In contrast, in RCC cells, TSP1 colocalized with COPI vesicles, pointing to the retrograde transport to the endoplasmic reticulum caused by misfolding. Our study indicates that TRPC4 loss in RCC leads to impaired Ca 2+ intake, misfolding, retrograde transport and diminished secretion of antiangiogenic TSP1, thus enabling angiogenic switch during RCC progression.

Metastasis-associated protein 1 (MTA1), a negative epigenetic modifier, plays a critical role in prostate cancer (PCa) progression. We hypothesized that MTA1 overexpression in primary tumor tissues can predict PCa aggressiveness and metastasis. Immunohistochemical staining of MTA1 was done on archival PCa specimens from University of Mississippi Medical Center and University of Iowa. We found that nuclear MTA1 overexpression was positively correlated with the severity of disease progression reaching its highest levels in metastatic PCa. Nuclear MTA1 overexpression was significantly associated with Gleason > 7 tumors in African Americans but not in Caucasians. It was also a predictor of recurrent disease. We concluded that MTA1 nuclear overexpression may be a prognostic indicator and a future therapeutic target for aggressive PCa in African American men. Our findings may be useful for categorizing African American patients with a higher probability of recurrent disease and metastasis from those who are likely to remain metastasis-free.

SMGs and basal SC compartments are depleted in large and/or small airways of lung allografts, and basal SC proliferative capacity declines with progression of disease and phenotypic changes. Global airway SC depletion may be a mechanism for pulmonary allograft failure.

N‐vinylcarbazole (NVC) was polymerized by 13X zeolite alone in melt (65°C) or in toluene (110°C) and a poly(N‐vinylcarbazole) (PNVC)‐13X composite was isolated. Composites of polypyrrole (PPY) and polyaniline(PANI) with 13X zeolite were prepared via polymerization of the respective monomers in the presence of dispersion of 13X zeolite in water (CuCl2 oxidant) and in CHCl3 (FeCl3 oxidant) at an ambient temperature. The composites were characterized by Fourier transform infrared analyses. Scanning electron microscopic analyses of various composites indicated the formation of lumpy aggregates of irregular sizes distinct from the morphology of unmodified 13X zeolite. X‐ray diffraction analysis revealed some typical differences between the various composites, depending upon the nature of the polymer incorporated. Thermogravimetric analyses revealed the stability order as: 13X‐zeolite > polymer‐13X‐zeolite > polymer. PNVC‐13X composite was essentially a nonconductor, while PPY‐13X and PANI‐13X composites showed direct current conductivity in the order of 10−4 S/cm in either system. However, the conductivity of PNVC‐ 13X composite could be improved to 10−5 and 10−6 S/cm by loading PPY and PANI, respectively. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 913–921, 2006

Purpose Progestins have been used in the treatment of recurrent endometrial adenocarcinoma for almost 50 years. Some endometrial carcinomas respond to hormonal therapy, but the mechanism of action remains incompletely known. We wished to determine the efficacy of progestins to induce a histologic response in endometrioid carcinomas and explore its effects on histologic and immunohistochemical measures of growth and cell death. Methods The Gynecologic Oncology Group initiated a study of 75 women with endometrioid endometrial adenocarcinoma, 59 of whom received the progestin, medroxyprogesterone acetate (MPA) for 21-24 days immediately prior to hysterectomy and had available slides. Initial biopsies and hysterectomies were H&E stained and immunostained for estrogen receptor (ER) and progesterone receptor (PR), progesterone receptor Beta (PRB), Bcl-2, Ki-67, and cleaved caspase-3 (Casp3). A histologic response was defined subjectively, following which specific histologic measurements and semi-quantitative scores of immunohistologic variables of initial biopsies were compared to post-treatment slides. Results Only one complete histologic response was seen, but 37 tumors (63%) had a partial histologic response. Specific histologic changes included the following: a decrease in the nuclear grade, the number of mitotic figures, nucleoli, and mean gland cellularity, and acquisition of more abundant eosinophilic cytoplasm, squamous metaplasia, and secretion. The tumors that displayed a subjectively defined histologic response following treatment differed initially from those that did not only with respect to initial nuclear grade and the mitotic index. Statistically significant differences in the specific histologic features in carcinomas of responders versus non-responders following treatment were found only with respect to acquisition of pale eosinophilic cytoplasm and luminal secretion. More than 90% of tumors were initially ER positive and 76% were PR positive. The initial presence of ER or PR was not related to subjective histologic response. PR and PRB were significantly down-regulated following progestin therapy, as were Ki-67 and Bcl-2. However, ER ad Casp3 did not change significantly. Tumors that displayed a histologic response had significantly lower pre-treatment levels of Ki-67. Mean Ki-67 and Bcl-2 decreases following MPA were greater in histologic responders than non-responders, but not decreases in ER, PR, PRB and Casp3. The histologic response in the tumors and their stroma differed quantitatively and qualitatively from that of the adjacent benign endometrium, where decidual change accompanied luminal secretion and secretory exhaustion of glands. Conclusion Three weeks of MPA therapy induces partial histologic responses in most endometrioid adenocarcinomas. Previously suggested features of histologic response do not capture the entire spectrum of changes seen. Down regulation of ER, PR, PRB, Ki-67 and Bcl-2 occurs without a significant change in Casp3. These alterations suggest that progestins act ...

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