Papillary thyroid carcinoma oncogene (RET/PTC) alters the nuclear envelope and chromatin structure.

Current evidence suggests the papillary thyroid carcinoma oncogene (RET/PTC) generates papillary thyroid carcinomas in one genetic step. We tested a resulting prediction that RET/PTC expression in thyroid epithelium should be sufficient to cause the changes in nuclear morphology diagnostic of this tumor. Primary cultures of human thyroid epithelial cells were infected with a RET/PTC retroviral construct. Morphological scoring by two independent cytopathologists shows RET/PTC expression by immunohistochemistry to be highly associated (p << 0.0001) with an irregular nuclear contour and a euchromatic appearance compared with non-expressing cells in the same cultures. The altered nuclear morphology is not due to gene transfer or transformation per se as primary thyroid cell cultures infected with a retroviral H-RAS construct differ from RET/PTC-infected cells by showing round nuclear envelopes and coarser chromatin, as determined by the independent scoring of two cytopathologists (p << 0.0001). In addition, RET/ PTC-transfected cells appear to disperse, whereas RAS-transfected cells grow as discrete colonies. The results provide additional support for the hypothesis that RET/PTC is sufficient to cause papillary thyroid carcinomas. A signaling pathway downstream of RET/ PTC leads to restructuring of the nuclear envelope and chromatin, and the signal does not depend entirely, if at all, on a RAS pathway.

Cytokeratins, CEA, and mucin histochemistry in the diagnosis and characterization of extramammary Paget's disease.

To identify a sensitive marker for extramammary Paget's disease and to identify histochemical and immunohistochemical features that suggest occult pelvic cancer in patients with extramammary Paget's disease, we retrieved all cases between 1983 and 1992 with a Standardized Nomenclature of Medicine code of extramammary Paget's disease in the Vanderbilt University Medical Center (Nashville, Tenn) surgical pathology archives. All were stained for alcian blue/dPAS (periodic acid-Schiff), mucicarmine, AE1/AE3, cytokeratin (CAM 5.2), cytokeratin (CK) 7, CK 20, carcinoembryonic antigen (CEA), orthokeratin, prostate-specific antigen, and S-100. Sixteen cases (2 men, 14 women) were retrieved. Two had pelvic malignancies: one rectal adenocarcinoma and one transitional carcinoma. Only CK7 marked all cases. Mucins were sensitive but focal, a potential problem in small biopsy specimens. The transitional tumor had a unique staining profile (CEA- and mucin-negative). CK20 strongly marked Paget cells associated with rectal cancer; its presence suggests a large bowel lesion but is not specific. No case expressed prostate-specific antigen; its presence in a man suggests prostatic carcinoma.