Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells.

Background: Accumulating evidence suggests that somatic stem cells undergo mutagenic transformation into cancer initiating cells. The serous subtype of ovarian adenocarcinoma in humans has been hypothesized to arise from at least two possible classes of progenitor cells: the ovarian surface epithelia (OSE) and/or an as yet undefined class of progenitor cells residing in the distal end of the fallopian tube.

Methods: Comparative gene expression profiling analyses were carried out on OSE removed from the surface of normal human ovaries and ovarian cancer epithelial cells (CEPI) isolated by laser capture micro-dissection (LCM) from human serous papillary ovarian adenocarcinomas.

Defining the cut point between low-grade and high-grade ovarian serous carcinomas: a clinicopathologic and molecular genetic analysis.

A 2-tier grading system based on nuclear grade divides ovarian serous carcinomas into low (nuclear grade 1) and high grade (nuclear grade 3). In most instances the separation is straightforward but at times, the morphologic distinction between them can be difficult. We studied 11 ovarian serous carcinomas with features that were "intermediate" (nuclear grade 2) between low and high grade.

Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells.

Background: A large percentage of patients with recurrent ovarian cancer develop resistance to the taxane class of chemotherapeutics. While mechanisms of resistance are being discovered, novel treatment options and a better understanding of disease resistance are sorely needed. The mitotic kinase Aurora-A directly regulates cellular processes targeted by the taxanes and is overexpressed in several malignancies, including ovarian cancer.

Intravascular lymphoma: an unusual diagnostic outcome of an incidentally detected adrenal mass.

Objective: To describe a rare diagnosis of intravascular lymphoma in a patient presenting with an incidentally discovered adrenal mass.

Methods: We describe the patient's clinical history and the findings from biochemical evaluation, radiologic studies, and surgical pathology and review the relevant literature.

Results: A 43-year-old woman developed sudden onset of flank pain associated with a flushing sensation and presented to the emergency department where computed tomography showed a 5-cm left adrenal mass.

Melanoma with cartilaginous differentiation: Diagnostic challenge on fine-needle aspiration with emphasis on differential diagnosis.

Fine-needle aspiration (FNA) is a minimally invasive, fast, and accurate diagnostic method for the evaluation of patients with locally recurrent or distant metastases of malignant melanoma. In the vast majority of cases, the diagnosis is straightforward with the characteristic cytologic features well documented in the literature. Divergent differentiation (chondroid, neural, myofibroblastic, and osteocartilagenous) in a melanoma is rare and can potentially create diagnostic challenges if the evaluator is unaware of the same.

Utilization of ancillary studies in thyroid fine needle aspirates: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference.

The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine Needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.

Vascular "pseudo invasion" in laparoscopic hysterectomy specimens: a diagnostic pitfall.

Total laparoscopic hysterectomy has been shown to be an equally effective and safe technique when compared with conventional abdominal surgery for endometrial carcinoma. The procedure, as performed at our institution, involves the use of a uterine balloon manipulator (RUMI manipulator and Koh Colpotomizer system) for optimal surgical control. The fallopian tubes are cauterized to prevent transtubal spread of the tumor.

The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis.

Recently, we have proposed a model for the development of ovarian surface epithelial tumors. In this model, all histologic types of surface epithelial tumors are divided into 2 categories designated type I and type II which correspond to 2 pathways of tumorigenesis. Type I tumors include low-grade serous carcinoma, mucinous carcinoma, endometrioid carcinoma, malignant Brenner tumor, and clear cell carcinoma which develop slowly in a stepwise fashion from well-recognized precursors, namely atypical proliferative (borderline) tumors.

Cytologic diagnosis of atypical squamous cells of undetermined significance in perimenopausal and postmenopausal women: lessons learned from human Papillomavirus DNA testing.

Background: The authors have noted that in cervical cytology specimens from perimenopausal and postmenopausal women, the diagnosis of atypical squamous cells of undetermined significance (ASC-US), as defined in the Bethesda system, is often not associated with a clinically evident lesion on follow-up. Reflex human papillomavirus (HPV) testing provides an opportunity to distinguish cytologic features of significance from those within the spectrum of benign cellular change in this age group.

Methods: Liquid-based preparations that were diagnosed as ASC-US between January 2003 and July 2005 at Emory University Hospital were identified from the computer files.

Evidence that p53-mediated cell-cycle-arrest inhibits chemotherapeutic treatment of ovarian carcinomas.

Gene expression profiles of malignant tumors surgically removed from ovarian cancer patients pre-treated with chemotherapy (neo-adjuvant) prior to surgery group into two distinct clusters. One group clusters with carcinomas from patients not pre-treated with chemotherapy prior to surgery (C-L), while the other clusters with non-malignant adenomas (A-L). We show here that although the C-L cluster is preferentially associated with p53 loss-of-function (LOF) mutations, the C-L cluster cancer patients display a more favorable clinical response to chemotherapy as evidenced by enhanced long-term survivorships.

Well-differentiated fetal adenocarcinoma of the lung: cytomorphologic features on fine-needle aspiration with emphasis on use of beta-catenin as a useful diagnostic marker.

Well-differentiated fetal adenocarcinoma (WDFA), also known as low grade adenocarcinoma of the fetal lung type, is a rare pulmonary neoplasm now considered to be a variant of lung adenocarcinoma rather than a type of pulmonary blastoma. Upregulation of the Wnt signaling pathway with subsequent aberrant nuclear/cytoplasmic beta-catenin expression has been recently described in these tumors providing a possible pathogenetic role for this gene in WDFA. We describe the cytomorphologic findings of a case of WDFA in a 36-yr-old female patient and emphasize the diagnostic utility of aberrant nuclear/cytoplasmic expression of beta-catenin as an adjunct to the correct preoperative recognition of this tumor on aspiration cytology.

Emerging roles for PAX8 in ovarian cancer and endosalpingeal development.

Objectives: Epithelial ovarian carcinomas develop from ovarian surface epithelia that undergo complex differentiation to form distinguishable phenotypes resembling those of the epithelia of the female urogenital regions. While previous studies have implicated regulatory developmental homeobox (HOX) genes in this process, other factors responsible for this differentiation are largely unknown. Aberrant transcriptional expression of PAX8 has been reported in epithelial ovarian cancer, prompting us to initiate the molecular characterization of this master regulatory gene in ovarian cancer development.

Oxidative stress induces ADAM9 protein expression in human prostate cancer cells.

The ADAM (a disintegrin and metalloprotease) family is a group of transmembrane proteins containing cell adhesive and proteolytic functional domains. Microarray analysis detected elevated ADAM9 during the transition of human LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent and metastatic state. Using a prostate tissue array (N = 200), the levels of ADAM9 protein expression were also elevated in malignant as compared with benign prostate tissues.

Immunohistochemical detection of p16INK4a in dysplastic lesions of the oral cavity.

Significant intra- and interobserver variability exists in diagnosing and grading oral epithelial dysplasia. Mutations in the tumor-suppressor gene p16 are common in oral cavity dysplastic lesions, but whether immunohistochemical detection of the gene product p16(INK4a) (p16) can be used as a reliable biomarker for dysplasia is unclear. In total, 119 biopsy specimens representing various oral cavity sites and degrees of dysplasia were retrieved from the pathology files of Emory University Hospital.

Evaluation of the CD34 and CD10 immunostains using a two-color staining protocol in liver fine-needle aspiration biopsies.

Fine-needle aspiration (FNA) biopsies of liver masses may need immunohistochemistry to resolve difficult cases. We examined liver FNAs with CD10 and CD34 using a two-color staining protocol. Fifty-one cases of hepatocellular carcinoma (HCC) and 23 cases of liver metastases were stained first with CD10 using diaminobenzidine as a chromogen and then with CD34 using Fast Red.

Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma.

Distinguishing primary ovarian carcinoma, particularly endometrioid and mucinous subtypes, from metastatic colorectal carcinoma to the ovary is often difficult on histologic examination alone. Recently, three immunohistochemical markers CDX2, a homeobox gene encoding an intestine-specific transcription factor; alpha-methylacyl-CoA racemase (AMACR/P504S), a mitochondrial and peroxisomal enzyme with fairly restricted expression in selective tumors and beta-catenin, an adenomatous polyposis coli (APC) mutation product resulting in activation of the Wnt pathway, have been reported to have specific and sensitive expression in colorectal carcinomas. We evaluated a panel consisting of antibodies to CDX2, beta-catenin and P504S in 23 primary ovarian adenocarcinomas (13 mucinous and 10 endometrioid) and compared the findings to 22 metastatic colorectal adenocarcinomas (seven mucinous and 15 nonmucinous tumors with endometrioid-like morphology hereafter referred to as pseudo-endometrioid) to the ovary stained with the same panel.

Molecular characterization of uterine clear cell carcinoma.

Clinicopathological studies support a broad classification of endometrial carcinoma into two major types, designated as type I and type II, which correlate with their biological behavior. More recently, molecular studies have provided further insights into this classification scheme by elucidating the genetic events involved in the development and progression of endometrial carcinoma. Microsatellite instability and mutations in the PTEN gene have been widely associated with type I (endometrioid) endometrial carcinoma, while p53 mutations have been identified in the majority of type II endometrial carcinoma, of which uterine serous carcinoma is the prototype.

Immunoprofile of ovarian tumors with putative transitional cell (urothelial) differentiation using novel urothelial markers: histogenetic and diagnostic implications.

Ovarian tumors containing cells with transitional cell morphology are recognized in the 1999 World Health Organization classification of ovarian tumors and include benign Brenner tumor, borderline and malignant Brenner tumor, and transitional cell carcinoma. Recent immunohistochemical investigations have reached conflicting conclusions regarding true urothelial differentiation in ovarian Brenner tumors. We evaluated a panel consisting of antibodies to uroplakin III (UROIII), thrombomodulin (THR), cytokeratin 7 (CK7), cytokeratin 20 (CK20), and Wilms' tumor protein (WT1) to study urothelial differentiation in ovarian transitional cell tumors.

Low-grade vulvar and vaginal intraepithelial neoplasia: correlation of histologic features with human papillomavirus DNA detection and MIB-1 immunostaining.

Histologic criteria of low-grade vulvar/vaginal intraepithelial neoplasia (VIN1/VAIN1) are well established; however, a significant interobserver variability in diagnosing VIN1/VAIN1 has been reported. The goal of this study was to evaluate the utility of MIB-1 immunostaining as an adjunct test to increase the diagnostic accuracy in equivocal cases of VIN1/VAIN1. The second goal was to examine the distribution of low- and high-oncogenic risk human papillomaviruses (HPVs) in VIN1/VAIN1 lesions.