The screening of women by Pap smear has led to a remarkable decline in the mortality from cervical cancer; however, secondary to subjective criteria, interpretation of Pap smears is subject to marked inter-and intraobserver variability as well as having a relatively low sensitivity for cervical neoplasia on a single sample (as low as 66% sensitivity for biopsy-proven high-grade squamous intraepithelial lesions [HSIL]) (1, 2). Recently, histology, which is thought of as the gold standard for the diagnosis of cervical neoplasia, has also been found to suffer from marked intra-and interobserver variability, and testing for high-risk human papillomavirus (HPV) by Hybrid Capture 2, which has been shown to be very sensitive in the detection of cervical neoplasia and useful in the triaging of ASCUS smears, has a low specificity for cervical neoplasia (1, 3). Thus, new biomarkers that are more sensitive and specific in the detection of cervical neoplasia and more reproducible than cervical cytology are needed. Human papillomaviruses (HPV) are known to be a major causative agent in cervical neoplasia and invasive cervical carcinoma. Many different HPV types associated with cervical neoplasia have been

Thyroid transcription factor-1 (TTF-1) is a nuclear homeodomain transcription factor that is expressed in the developing thyroid, respiratory epithelium, and diencephalon. TTF-1 is thought to be expressed specifically in pulmonary or thyroid neoplasms, and it is expressed in a significant subset of pulmonary non-small cell carcinomas, small cell carcinomas, and carcinoids but not in nonpulmonary, nonsmall cell carcinomas. Neuroendocrine tumors from sites other than the lung have not been evaluated for TTF-1 expression. We examined TTF-1 expression using immunohistochemistry on formalin-fixed, paraffin-embedded sections of 49 gastrointestinal carcinoids; 15 pancreatic islet cell tumors; 21 paragangliomas; 8 medullary thyroid carcinomas; 7 small cell carcinomas of the uterine cervix; 4 prostate, 4 bladder, and 6 Merkel cell (primary cutaneous neuroendocrine) carcinomas; and 1 renal carcinoma. No gastrointestinal carcinoid tumor, pancreatic islet cell tumor, paraganglioma, or Merkel cell carcinoma expressed TTF-1. All of the medullary thyroid carcinomas strongly expressed TTF-1. However, 44% of nonpulmonary small cell carcinomas were also TTF-1 positive, including four of four prostate, two of four bladder, and one of seven cervical small cell carcinomas. We conclude that TTF-1 expression is not specific for small cell carcinomas of pulmonary origin and should not be used to distinguish primary from metastatic small cell carcinomas in extrapulmonary sites. However, TTF-1 expression may be useful in distinguishing Merkel cell carcinomas and cutaneous metastasis of small cell carcinomas. Among well-differentiated neuroendocrine tumors, TTF-1 expression seems to be present only in carcinoid tumors of the lung and medullary carcinomas of the thyroid and may be of differential diagnostic value when dealing with a metastatic well-differentiated neuroendocrine tumor.

We sought to determine the prevalence of androgen receptor (AR) expression in a predominantly estrogen receptor (ER)-negative subset of breast cancers and delineate the immunohistochemical and clinical associations, including whether AR expression has prognostic significance in ER-negative tumors. We identified 69 ER-negative and 19 ER-positive breast cancer cases with concurrent immunohistochemical prognostic panels (ER, PR, HER-2/neu, Ki-67, and p53); immunohistochemical analysis was performed for AR using standard techniques. Clinical data were extracted from medical records. chi 2 tests were used to assess associations between variables. AR was found in 49% (34/69) of ER-negative and 89% (17/19) of ER-positive cases. In ER-negative tumors, AR was associated with increased age (P = .02), postmenopausal status (P < .001), tumor grade (P = .03), tumor size (P = .03), and HER-2/neu overexpression (P = .003). In ER-positive tumors, AR was associated with progesterone receptor expression (P < .03). In univariate analysis of ER-negative tumors, patients with AR-positive tumors had significantly better disease-free survival (P = .049). AR is expressed in a significant number of ER-negative cases and shows significant associations with important clinical and pathologic prognostic factors.

The tumor suppressor p53 is a nuclear phosphoprotein with characteristics of a transcription factor. It displays sequence-specific DNA binding, contains a potent transactivation domain, and has been implicated as both a transcriptional activator and a repressor. Transcription of the human hsp70 gene is stimulated by adenovirus E1a protein. This E1a transactivation of the hsp70 promoter is mediated by CCAAT binding factor (CBF). It is demonstrated here that p53 both represses transcription from the human hsp70 promoter and also interacts with CBF. Thus, the repression of the hsp70 promoter by p53 may be mediated by direct protein-protein interaction with CBF. These results suggest that protein-protein interaction between p53 and specific transcription factors may be an additional mechanism by which p53 regulates gene expression.

Parachordoma is a rare soft-tissue tumor resembling extraskeletal myxoid chondrosarcoma and chordoma. Because fewer than 30 cases have been reported and precisely characterized, we studied the clinicopathologic features of seven new cases, comparing the immunohistochemical (six cases) and cytogenetic (one case) profiles with 15 cases of chordoma and six cases of extraskeletal myxoid chondrosarcoma. Patients with these tumors ranged in age from 7 to 62 years (mean, 35 years) and included four women and three men. The tumors presented as subfascial masses of the thigh (two cases), arm (three cases), chest wall (one cases), and buttocks (one case). In six of seven cases, there was neither recurrence nor metastasis within the follow-up, which ranged from 4 months to 7 years. The tumors were composed of vague nodules of large, rounded eosinophilic cells embedded in a matrix that varied from myxoid to densely hyaline, and the latter areas occasionally resembled primitive cartilage. Transitions between the large eosinophilic cells and smaller rounded and shorter spindled ones were often noted. Multivacuolated (physaliferouslike) cells were noted in all cases but were usually few in number. The matrix stained with Alcian blue (pH 2.5), and this staining was abolished with hyaluronidase predigestion. Immunohistochemistry for a variety of cytokeratins (CKs) (8/18, 1/10, 7, and 20), epithelial membrane antigen (EMA), S-100 protein, vimentin CD34, type IV collagen, smooth muscle actin, smooth muscle myosin heavy chain, calponin, and glial fibrillary acid protein was performed. All parachordomas strongly expressed CK 8/18, but not the other cytokeratins. Additionally, they expressed EMA (five of six). S-100 protein (six of six), and vimentin (six of six) and had a linear pattern of type IV collagen immunoreactivity around nests of cells (four of five). Calponin was noted in one case, but no cases expressed smooth muscle actin, smooth muscle myosin heavy chain, or glial fibrillary acid protein. In contrast, chordoma expressed CK 8/18 (15 of 15) and CK 1/10 (14 of 15), whereas extraskeletal myxoid chondrosarcoma consistently lacked CK. Although chordoma and extraskeletal myxoid chondrosarcoma showed considerable overlap with parachordoma, with respect to EMA and S-100 protein, they infrequently displayed type IV collagen, as was seen in parachordoma. One case of parachordoma studied cytogenetically disclosed trisomy 15, and monosomies of 1, 16, and 17 in contrast to the t(9;22) reported in extraskeletal myxoid chondrosarcoma and the monosomies of 3, 4, 10, and 13 seen in chordoma. We conclude that the immunohistochemical and cytogenetic profile distinguishes parachordoma from extraskeletal myxoid chondrosarcoma and chordoma. Lack of myoepithelial markers, furthermore, suggests parachordoma is not a deeply situated adnexal tumor. Because of these differences, parachordoma is best regarded as a distinct lesion without a clear relationship to other well-characterized tumors.