Faculty Bibliography

Myxoid lipoadenoma of the parathyroid gland is a rare variant of parathyroid adenoma. We present the case of a 40-year-old man with asymptomatic hypercalcemia who underwent surgical removal of a parathyroid adenoma. Histologically, the tumor consisted of monomorphous round-to-oval chief cells arranged in several architectural patterns including solid sheet-like, trabecular, and follicular. The tumor stroma was prominently myxoid with interspersed mature adipose tissue. Immunohistochemistry confirmed expression of thyroid transcription factor and parathyroid hormone by all tumor cells and a low proliferation rate with a Ki-67 labeling index of at most 5%. Although the lesion exhibited characteristics that have been previously associated with 'atypical parathyroid adenoma,' such as dense fibrous bands within the tumor and a trabecular growth pattern, there was no further evidence, neither histologically nor clinically, for malignant behavior of the tumor

BACKGROUND: Neutral endopeptidase (NEP) is a cell-surface peptidase that can regulate the activation of Akt kinase through catalytic-dependent and independent mechanisms. NEP expression is absent in approximately 50% of prostate cancers. The authors investigated whether NEP loss in vivo would result in Akt phosphorylation and potentially contribute to prostate cancer progression by examining the interaction of NEP, Akt, and phosphatase and tensin homolog (PTEN) in a prostate xenograft model and in clinical specimens from patients with prostate cancer. METHODS: Using a tetracycline-repressible expression system to express NEP in a tumor animal xenograft model, the effects of NEP were tested on tumor growth, Akt phosphorylation, and PTEN expression. The clinical relevance of NEP, phosphorylated Akt, and PTEN protein expression also was investigated in 204 patients who had undergone radical prostatectomy. RESULTS: The results indicated that the induction of NEP expression inhibited established xenograft tumor growth, diminished Akt phosphorylation, and increased PTEN protein levels. In humans, prostate cancers with complete loss of NEP expression were significantly more likely to express phosphorylated Akt (P = .02). Moreover, patients who had prostate cancers with concomitant loss of NEP and expression of phosphorylated Akt had an increased, independent risk of prostate-specific antigen (PSA) recurrence (P = .03). In the study cohort, loss of PTEN protein expression did not correlated significantly with phosphorylated Akt or with patients' clinical outcome. CONCLUSIONS: The findings from this investigation demonstrated that NEP loss leads to Akt activation and contributes to the clinical progression of prostate cancer

Background: Androgens have been implicated in androgenic alopecia as evidenced by the increased cutaneous expression of androgen receptor (AR), 5alpha-reductase, and decreased aromatase. Abnormalities of the AR-signal transduction pathway probably participate in the development of androgenic alopecia. ARA70/ELE1 is an AR coactivator with two isoforms, one full-length form (ARA70alpha/ELE1alpha), and an internally deleted form (ARA70beta/ELE1beta). We decided to examine the cutaneous expression of both isoforms in male androgenic alopecia. Methods: Formalin-fixed, paraffin-embedded tissue sections from seven subjects with androgenic alopecia with matched punch biopsies from non-balding and balding areas were examined by in situ hybridization. Results: Expression of at least one of the two probes for ARA70/ELE1 was present in all phases of the hair-growth cycle in all epithelial hair structures except for the inner root sheath. The dermal papilla and hair bulb expressed only the short (beta) but not the long (alpha) form of ARA70/ELE1. In situ labeling for ARA70beta/ELE1beta was weaker in the dermal papilla of balding recipient areas than those from donor ones. Conclusions: Our data further support that the hair growth is regulated by androgens. The differential expression pattern of ARA70/ELE1 suggests that this key androgen receptor coactivator is involved in androgenic alopecia. Lee P, Zhu C-C, Sadick NS, Diwan AH, Zhang PS, Liu JS, Prieto VG. Expression of androgen receptor coactivator ARA70/ELE1 in androgenic alopecia

Squamous cell carcinoma of the esophagus (ESCC), a major subtype of esophageal carcinoma, is one of the aggressive cancers with worst prognosis in the world. The dismal outcome of ESCC is attributed to multiple reasons including its aggressive nature, largely unknown molecular mechanism of its progression, and the lack of biomarkers for early detection and effective prediction of its clinical behavior. To identify proteins with prognostic and/or predictive value, we applied a proteomics strategy to quantify proteins differentially expressed in ESCC using matched samples of carcinoma and adjacent normal epithelial cells. The analysis led to identification of 28 proteins aberrantly expressed in cancer cells with changes of at least three-fold in ESCC relative to normal squamous epithelial cells. These changes represent functional alterations of essential proteins for normal cellular physiology, accounting for many cellular changes involved in development of ESCC, including cell transformation, loss of differentiation, tumor growth, apoptosis, tumor invasion, and cell metabolism. The differentially expressed proteins shed new insights on the mechanism of tumorigenesis and provide candidate biomarkers for early detection of ESCC

OBJECTIVE: Receptors for estrogen (ER), progesterone (PR), or androgen (AR) are predictive and prognostic markers of malignancy of multiple endocrine organs, including endometrial and breast cancer. However, the role of ERs, PRs, or ARs in the carcinogenesis of ovarian cancer, another sex hormone-dependent malignancy, is still controversial despite numerous studies that have attempted to determine their role. The disagreement in the findings may result from the fact that the numbers of tumor samples in studies have been small and that different immunohistochemical methods have been used that can introduce variation in the scoring of the histology. We therefore examined the pattern of expression of ERs, PRs, and ARs in a large number of samples of primary ovarian carcinoma by using a tissue microarray technique. METHODS: We constructed a tissue microarray with 322 samples of primary ovarian carcinoma obtained at surgery performed at The University of Texas M. D. Anderson Cancer Center between 1990 and 2000. Immunohistochemistry studies were performed by using the immunoperoxidase technique against primary antibodies (ER, PR, and AR). RESULTS: ERs, PRs, and ARs were differently expressed in different histotypes of ovarian cancer: ERs were expressed in 77.3% of all cases but more highly expressed in serous and endometrioid types; PRs were expressed in 26.2% of all cases but most highly expressed in the endometrioid type < 64.2%; and ARs were expressed in 43.7% of all cases but were most highly expressed in serous (47.5%) carcinomas. Of particular importance, the expression of PRs, but not ERs or ARs, was associated with better survival (P < 0.0001) in univariate and multivariate analyses. CONCLUSIONS: The PR is an independent marker, with its overexpression associated with a favorable prognosis in women with ovarian cancer

Abstract Adenomatoid tumors are relatively uncommon benign neoplasms of mesothelial origin, usually occurring in the male and female genital tracts. Rare extragenital adenomatoid tumors have been identified in the adrenal glands, heart, mesentery, pleura, and lymph nodes. In the adrenal gland, adenomatoid tumors may pose a diagnostic challenge. The differential diagnosis includes adrenocortical carcinoma and metastatic carcinoma, especially signet ring cell carcinoma. Because of its glandular pattern, an adenomatoid tumor may be confused with an adenocarcinoma. We present 3 cases of adrenal adenomatoid tumors, including one with a concurrent large hemorrhagic vascular adrenal cyst. The adenomatoid tumors were unilateral, appeared solid and white, and varied from 1.7 to 4.2 cm in diameter. They occurred in 3 male patients aged 33, 33, and 46 years. One patient presented with abdominal pain due to the presence of a concurrent large adrenal cyst. The tumor was an incidental radiological finding in another case and was discovered during the course of a workup for hypertension in the third case. The light microscopic appearances were consistent with those of typical adenomatoid tumors. Immunohistochemical stains for calretinin and cytokeratin 5/6 were positive, confirming the tumors' mesothelial origin. Ultrastructural studies performed in 2 cases revealed microvilli and desmosomes. Follow-up showed no evidence of recurrence or metastasis. In our experience, the key to the diagnosis of this rare benign tumor is to consider adenomatoid tumor in the differential diagnosis of any glandular tumor occurring in the adrenal gland

Androgens provide survival signals to prostate epithelial cells, and androgen ablation induces apoptosis in the prostate gland. However, the molecular mechanisms of actions of the androgen-signaling pathway in these processes are not fully understood. Here, we report that androgens induced expression of the cellular FLIP (c-FLIP) gene, which is a potent inhibitor of Fas/FasL-mediated apoptosis. The androgen receptor (AR) was recruited to the promoter of the c-FLIP gene in the presence of androgens. We found that c-FLIP promoter contained multiple functional androgen response elements (AREs). In addition, we show that c-FLIP overexpression accelerated progression to androgen independence by inhibiting apoptosis in LNCaP prostate tumors implanted in nude mice. Our results suggest that AR affects survival and apoptosis of prostate cells through regulation of the c-FLIP gene in response to androgens