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1.
Oncogene ; 36(47): 6592-6604, 2017 11 23.
Article in English | MEDLINE | ID: mdl-28783170

ABSTRACT

The hyperactivated Wnt/ß-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear. In current study, we have discovered, using a comprehensive investigative regimen, a novel and tissue-specific role of claudin-3, a tight junction integral protein, in inhibiting colon cancer progression by serving as the common rheostat of Stat-3 and Wnt-signaling activation. Loss of claudin-3 also predicted poor patient survival. These findings however contrasted an upregulated claudin-3 expression in other cancer types and implicated role of the epigenetic regulation. Claudin-3-/- mice revealed dedifferentiated and leaky colonic epithelium, and developed invasive adenocarcinoma when subjected to colon cancer. Wnt-signaling hyperactivation, albeit in GSK-3ß independent manner, differentiated colon cancer in claudin-3-/- mice versus WT-mice. Claudin-3 loss also upregulated the gp130/IL6/Stat3 signaling in colonic epithelium potentially assisted by infiltrating immune components. Genetic and pharmacological studies confirmed that claudin-3 loss induces Wnt/ß-catenin activation, which is further exacerbated by Stat-3-activation and help promote colon cancer. Overall, these novel findings identify claudin-3 as a therapeutic target for inhibiting overactivation of Wnt-signaling to prevent CRC malignancy.


Subject(s)
Adenocarcinoma/pathology , Claudin-3/metabolism , Colonic Neoplasms/metabolism , Colorectal Neoplasms/pathology , Wnt Signaling Pathway , beta Catenin/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Animals , Carcinogenesis/metabolism , Cell Transformation, Neoplastic , Claudin-3/genetics , Colon/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Cytokine Receptor gp130/metabolism , Epigenesis, Genetic , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Humans , Intestinal Mucosa/metabolism , Mice , Mice, Knockout , Permeability , STAT3 Transcription Factor/metabolism , Up-Regulation
2.
Cell Death Dis ; 7: e2297, 2016 07 14.
Article in English | MEDLINE | ID: mdl-27415427

ABSTRACT

The four and a half LIM domains 2 (FHL2) has been shown to play important roles in the regulation of cell proliferation, survival, adhesion, motility and signal transduction in a cell type and tissue-dependent manner. However, the function of FHL2 in ovarian physiology and pathology is unclear. The aim of this study was to determine the role and functional mechanism of FHL2 in the progression of ovarian granulosa cell tumors (GCTs). Immunohistochemical analysis indicated that FHL2 was overexpressed in GCT tissues. Cellular localization of FHL2 in GCT cells was cell cycle dependent. Knockdown of FHL2 suppressed GCT cell growth, reduced cell viability and inhibited cell migration. Consistently, ectopic expression of FHL2 in GCT cells with very low endogenous FHL2 promoted cell growth, improved cell viability and enhance cell migration. Importantly, overexpression of FHL2 promoted GCT progression in vivo. Mechanistic studies indicated that FHL2 regulates AKT1 gene expression in vitro and in vivo. Knockdown of FHL2 or AKT1 in GCT cell lines induced very similar phenotypes. Ectopic expression of constitutively active AKT1 rescued FHL2 knockdown-induced arrest of GCT cell growth and reduction of GCT cell viability, suggesting that FHL2 regulates GCT cell growth and viability through controlling AKT1 expression. Finally, co-immunoprecipitation and chromatin immunoprecipitation analyses indicated that FHL2 functions as a co-activator of NFκB and AP-1 to regulate AKT1 gene transcription. In conclusion, results from the present study indicate that FHL2 exerts its oncogenic action in GCT cells via controlling AKT1 gene expression. FHL2 is a promising target for the development of novel drugs against ovarian granulosa cell tumor.


Subject(s)
Cell Transformation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic , Granulosa Cell Tumor/genetics , LIM-Homeodomain Proteins/genetics , Muscle Proteins/genetics , Ovarian Neoplasms/genetics , Proto-Oncogene Proteins c-akt/genetics , Transcription Factors/genetics , Animals , Cell Line, Tumor , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Female , Genes, Reporter , Granulosa Cell Tumor/metabolism , Granulosa Cell Tumor/pathology , Humans , LIM-Homeodomain Proteins/antagonists & inhibitors , LIM-Homeodomain Proteins/metabolism , Luciferases/genetics , Luciferases/metabolism , Mice , Mice, Nude , Muscle Proteins/antagonists & inhibitors , Muscle Proteins/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Neoplasm Transplantation , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism , Transcription Factors/antagonists & inhibitors , Transcription Factors/metabolism , Transcription, Genetic
3.
Oncogene ; 35(17): 2247-65, 2016 04 28.
Article in English | MEDLINE | ID: mdl-26364602

ABSTRACT

Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In this study, we found that the Hippo/Yes-associated protein (YAP) signaling pathway has a critical role in the initiation and progression of fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine-positive feedback loop to drive the progression of the FTSEC-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGF receptors (such as BGJ398) can provide a novel therapeutic strategy to treat fallopian tube and ovarian HGSC.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Carcinogenesis/genetics , Cystadenocarcinoma, Serous/genetics , Fallopian Tube Neoplasms/genetics , Ovarian Neoplasms/genetics , Phosphoproteins/genetics , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Cell Movement/genetics , Cell Proliferation/genetics , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/pathology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Fallopian Tube Neoplasms/drug therapy , Fallopian Tube Neoplasms/pathology , Fallopian Tubes/metabolism , Fallopian Tubes/pathology , Female , Fibroblast Growth Factors/antagonists & inhibitors , Fibroblast Growth Factors/genetics , Gene Expression Regulation, Neoplastic/drug effects , Humans , Neoplasm Grading , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Phenylurea Compounds/administration & dosage , Phosphoproteins/antagonists & inhibitors , Porphyrins/administration & dosage , Pyrimidines/administration & dosage , Signal Transduction/genetics , Transcription Factors , Verteporfin , YAP-Signaling Proteins
5.
Oncogene ; 34(50): 6040-54, 2015 Dec 10.
Article in English | MEDLINE | ID: mdl-25798835

ABSTRACT

Mechanisms underlying ovarian cancer initiation and progression are unclear. Herein, we report that the Yes-associated protein (YAP), a major effector of the Hippo tumor suppressor pathway, interacts with ERBB signaling pathways to regulate the initiation and progression of ovarian cancer. Immunohistochemistry studies indicate that YAP expression is associated with poor clinical outcomes in patients. Overexpression or constitutive activation of YAP leads to transformation and tumorigenesis in human ovarian surface epithelial cells, and promotes growth of cancer cells in vivo and in vitro. YAP induces the expression of epidermal growth factor (EGF) receptors (EGFR, ERBB3) and production of EGF-like ligands (HBEGF, NRG1 and NRG2). HBEGF or NRG1, in turn, activates YAP and stimulates cancer cell growth. Knockdown of ERBB3 or HBEGF eliminates YAP effects on cell growth and transformation, whereas knockdown of YAP abrogates NRG1- and HBEGF-stimulated cell proliferation. Collectively, our study demonstrates the existence of HBEGF & NRGs/ERBBs/YAP/HBEGF & NRGs autocrine loop that controls ovarian cell tumorigenesis and cancer progression.


Subject(s)
Adaptor Proteins, Signal Transducing/physiology , Ovarian Neoplasms/etiology , Phosphoproteins/physiology , Receptor, ErbB-3/physiology , Signal Transduction , Animals , Cell Line, Tumor , Cell Proliferation , Disease Progression , ErbB Receptors/physiology , Female , Heparin-binding EGF-like Growth Factor/physiology , Humans , Mice , Prognosis , Transcription Factors , YAP-Signaling Proteins
6.
Oncogene ; 34(13): 1698-708, 2015 Mar 26.
Article in English | MEDLINE | ID: mdl-24747969

ABSTRACT

The limited effectiveness of therapy for patients with advanced stage head and neck squamous cell carcinoma (HNSCC) or recurrent disease is a reflection of an incomplete understanding of the molecular basis of HNSCC pathogenesis. MUC4, a high molecular weight glycoprotein, is differentially overexpressed in many human cancers and implicated in cancer progression and resistance to several chemotherapies. However, its clinical relevance and the molecular mechanisms through which it mediates HNSCC progression are not well understood. This study revealed a significant upregulation of MUC4 in 78% (68/87) of HNSCC tissues compared with 10% positivity (1/10) in benign samples (P=0.006, odds ratio (95% confidence interval)=10.74 (2.0-57.56). MUC4 knockdown (KD) in SCC1 and SCC10B HNSCC cell lines resulted in significant inhibition of growth in vitro and in vivo, increased senescence as indicated by an increase in the number of flat, enlarged and senescence-associated ß-galactosidase (SA-ß-Gal)-positive cells. Decreased cellular proliferation was associated with G0/G1 cell cycle arrest and decrease expression of cell cycle regulatory proteins like cyclin E, cyclin D1 and decrease in BrdU incorporation. Mechanistic studies revealed upregulation of p16, pRb dephosphorylation and its interaction with histone deacetylase 1/2. This resulted in decreased histone acetylation (H3K9) at cyclin E promoter leading to its downregulation. Orthotopic implantation of MUC4 KD SCC1 cells into the floor of the mouth in nude mice resulted in the formation of significantly smaller tumors (170±18.30 mg) compared to those (375±17.29 mg) formed by control cells (P=0.00007). In conclusion, our findings showed that MUC4 overexpression has a critical role by regulating proliferation and cellular senescence of HNSCC cells. Downregulation of MUC4 may be a promising therapeutic approach for treating HNSCC patients.


Subject(s)
Carcinoma, Squamous Cell/pathology , Cellular Senescence , Head and Neck Neoplasms/pathology , Mucin-4/physiology , Neoplasm Proteins/physiology , Retinoblastoma Protein/physiology , Animals , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Movement , Cell Proliferation , Chromatin Assembly and Disassembly , Cyclin E/analysis , Cyclin-Dependent Kinase Inhibitor p16 , Humans , Mice , Mucin-4/analysis , Neoplasm Invasiveness , Squamous Cell Carcinoma of Head and Neck
7.
Oncogene ; 31(7): 805-17, 2012 Feb 16.
Article in English | MEDLINE | ID: mdl-21785467

ABSTRACT

MUC16/CA125 is a tumor marker currently used in clinics for the follow-up of patients with ovarian cancer. However, MUC16 expression is not entirely restricted to ovarian malignancies and has been reported in other cancers including breast cancer. Although it is well established as a biomarker, function of MUC16 in cancer remains to be elucidated. In the present study, we investigated the role of MUC16 in breast cancer and its underlying mechanisms. Interestingly, our results showed that MUC16 is overexpressed in breast cancer tissues whereas not expressed in non-neoplastic ducts. Further, stable knockdown of MUC16 in breast cancer cells (MDA MB 231 and HBL100) resulted in significant decrease in the rate of cell growth, tumorigenicity and increased apoptosis. In search of a mechanism for breast cancer cell proliferation we found that MUC16 interacts with the ezrin/radixin/moesin domain-containing protein of Janus kinase (JAK2) as demonstrated by the reciprocal immunoprecipitation method. These interactions mediate phosphorylation of STAT3 (Tyr705), which might be a potential mechanism for MUC16-induced proliferation of breast cancer cells by a subsequent co-transactivation of transcription factor c-Jun. Furthermore, silencing of MUC16 induced G2/M arrest in breast cancer cells through downregulation of Cyclin B1 and decreased phosphorylation of Aurora kinase A. This in turn led to enhanced apoptosis in the MUC16-knockdown breast cancer cells through Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated extrinsic apoptotic pathway with the help of c-Jun N-terminal kinase signaling. Collectively, our results suggest that MUC16 has a dual role in breast cancer cell proliferation by interacting with JAK2 and by inhibiting the apoptotic process through downregulation of TRAIL.


Subject(s)
Apoptosis , Breast Neoplasms/metabolism , CA-125 Antigen/metabolism , Cell Proliferation , Janus Kinase 2/metabolism , Membrane Proteins/metabolism , Blotting, Western , Breast Neoplasms/genetics , Breast Neoplasms/pathology , CA-125 Antigen/genetics , Cell Division , Cell Line, Tumor , Cyclin B1/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Female , G2 Phase , Humans , Immunohistochemistry , JNK Mitogen-Activated Protein Kinases/metabolism , Janus Kinase 2/genetics , Membrane Proteins/genetics , Models, Biological , Phosphorylation , Protein Binding , RNA Interference , STAT3 Transcription Factor/metabolism , TNF-Related Apoptosis-Inducing Ligand/metabolism
8.
Br J Cancer ; 98(9): 1540-7, 2008 May 06.
Article in English | MEDLINE | ID: mdl-18392050

ABSTRACT

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26+/-2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer from non-cancer cases (area under curve=0.75). In conclusion, NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. Further, serum NGAL measurement could be investigated as a possible biomarker in pancreatitis and pancreatic adenocarcinoma.


Subject(s)
Acute-Phase Proteins/analysis , Adenocarcinoma/diagnosis , Biomarkers, Tumor/analysis , Carcinoma, Pancreatic Ductal/diagnosis , Lipocalins/analysis , Pancreatic Neoplasms/diagnosis , Proto-Oncogene Proteins/analysis , Acute-Phase Proteins/genetics , Adenocarcinoma/blood , Adenocarcinoma/chemistry , Adult , Aged , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Blotting, Western , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/chemistry , Cell Line, Tumor , Early Diagnosis , Enzyme-Linked Immunosorbent Assay , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Lipocalin-2 , Lipocalins/blood , Lipocalins/genetics , Male , Middle Aged , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/chemistry , Proto-Oncogene Proteins/blood , Proto-Oncogene Proteins/genetics , RNA, Neoplasm/analysis , ROC Curve , Reverse Transcriptase Polymerase Chain Reaction
9.
J Postgrad Med ; 53(2): 111-3, 2007.
Article in English | MEDLINE | ID: mdl-17495377

ABSTRACT

We report a case of an elderly woman who developed a severe, chronic pulmonary reaction to nitrofurantoin therapy that she had taken continuously for three years to prevent urinary tract infections. The patient was taking no other drug known to cause lung disease but the diagnosis was delayed by failure to recognize the association between nitrofurantoin and adverse drug reactions affecting the lung. When originally seen, the patient was unable to care for herself due to dyspnea. Bronchoscopy with biopsy ruled out other causes of her pulmonary disease. Immediate withdrawal of nitrofurantoin led to substantial, sustained improvement and disappearance of symptoms over several months without administration of corticosteroids. Nitrofurantoin toxicity should always be considered in any person taking that drug who develops bilateral infiltrates.


Subject(s)
Anti-Infective Agents, Urinary/adverse effects , Lung Diseases, Interstitial/chemically induced , Nitrofurantoin/adverse effects , Aged , Female , Humans , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/drug therapy
10.
J Comp Pathol ; 128(4): 289-92, 2003 May.
Article in English | MEDLINE | ID: mdl-12834613

ABSTRACT

The white-throated woodrat is a principal host of Whitewater Arroyo (WWA) virus, an arenavirus, in the western United States. The purpose of the present study was to investigate the pathology of WWA infection in this species. Twenty-one animals (eight newborn, seven juvenile, and six adult) were inoculated with WWA virus and killed at varying intervals after inoculation. The most striking histological findings were lymphocytic meningitis and perivascular lymphocytic cuffing in the brains of the animals killed on day 85, 113 or 121. Arenaviral antigen was detected immunohistochemically in the brain of each affected animal, suggesting that the inflammatory lesions in the brain were caused by WWA virus. Comparisons of the results of tests for infectious virus and antigen in brain and other solid tissues indicated that immunohistochemistry may be a useful method for detection of WWA viral antigen in post-mortem specimens.


Subject(s)
Arenaviridae Infections/pathology , Arenavirus , Rodent Diseases/pathology , Sigmodontinae , Animals , Animals, Newborn , Antigens, Viral/immunology , Arenaviridae Infections/immunology , Arenaviridae Infections/virology , Arenavirus/immunology , Arenavirus/isolation & purification , Cerebral Cortex/pathology , Cerebral Cortex/virology , Female , Immunohistochemistry , Kidney/pathology , Male , Meningitis/pathology , Meningitis/virology , Neurons/immunology , Neurons/pathology , Neurons/virology , Rats , Rodent Diseases/immunology , Rodent Diseases/virology , Time Factors
11.
Chest Surg Clin N Am ; 11(2): 233-53, ix, 2001 May.
Article in English | MEDLINE | ID: mdl-11413754

ABSTRACT

Developmental anatomy and developmental and acquired disorders of the thymus are presented with an emphasis on those disorders that are relevant to infancy and childhood. Presented also is an attempt to correlate functional anatomy and pathologic and clinical findings.


Subject(s)
Thymus Gland/growth & development , Thymus Gland/pathology , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Lymphatic Diseases/pathology , Lymphatic Diseases/surgery , Thymectomy , Thymus Gland/anatomy & histology , Thymus Neoplasms/pathology
12.
Appl Immunohistochem Mol Morphol ; 8(1): 32-6, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10937046

ABSTRACT

Maspin is a recently described member of the serpin family of protease inhibitors that is consistently expressed at high levels in mammary myoepithelial cells. This feature was used in the immunohistochemical evaluation of tubular carcinoma (TC) and radial sclerosing lesion (RSL) of the breast, and compared with other markers of myoepithelial cells. Ten cases of TC and 11 cases of RSL were studied for the expression of maspin, alpha-smooth muscle actin (alpha-SMA), metallothionein (MT), and S-100 protein by immunohistochemistry. Myoepithelial cells stained strongly and diffusely for maspin creating a pattern of an outer continuous ring surrounding the epithelium of tubules of all RSLs. This pattern was absent in all TCs; however, the single-layered epithelium comprising the tubules of two TCs was positive for maspin with a moderate to strong intensity. Myoepithelial cells were not positive for MT in a consistent manner. Benign nonproliferative epithelium stained focally and weakly for maspin in four of 11 cases of RSL and was negative for MT in all 11 cases. Foci of mild to moderate epithelial hyperplasia noted in five of 11 cases of RSL stained diffusely with a weak to moderate intensity for maspin and focally with a strong intensity for MT. alpha-SMA was consistently expressed in myoepithelial cells but also in stromal myofibroblasts and blood vessels, creating a pattern that was less satisfactory than maspin in distinguishing RSL from TC. Immunohistochemical staining for S-100 protein was of no differential diagnostic value. In conclusion, immunohistochemical staining for maspin is diagnostically useful and superior to MT, S-100, and alpha-SMA, in distinguishing RSL from TC. The epithelial immunoreactivity for maspin in two of 10 TCs merits further investigation from a prognostic viewpoint.


Subject(s)
Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast/metabolism , Breast/pathology , Proteins/metabolism , Serpins/metabolism , Biomarkers, Tumor/metabolism , Diagnosis, Differential , Epithelium/metabolism , Epithelium/pathology , Female , Genes, Tumor Suppressor , Humans , Immunohistochemistry , Metallothionein/metabolism , Sclerosis
13.
Diagn Cytopathol ; 23(3): 187-91, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10945907

ABSTRACT

The fine-needle aspiration biopsy (FNAB) findings in two cases of hemangiopericytoma (HP), arising in the parotid gland and on the inner chest wall, respectively, are reported. Smear preparations in each case showed cytologic features of an undifferentiated spindle-cell neoplasm, whereas a core needle biopsy specimen of the chest wall mass showed a spindle-cell tumor with a "staghorn-like" arrangement of endothelium-lined vascular channels. Immunostains performed on this core biopsy, and on the surgical resection specimens in both cases, showed positive staining of tumor cells for vimentin and CD34, with negative staining for a variety of smooth muscle, epithelial, neural, and neuroendocrine markers. Electron microscopy performed in one case further supported the diagnosis of HP. With adequate sampling and appropriate use of ancillary studies, a diagnosis of HP can be reliably suggested on the basis of FNAB and core biopsy of a soft-tissue mass.


Subject(s)
Hemangiopericytoma/diagnosis , Parotid Neoplasms/diagnosis , Thoracic Neoplasms/diagnosis , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Biopsy, Needle , Female , Hemangiopericytoma/chemistry , Hemangiopericytoma/radiotherapy , Hemangiopericytoma/surgery , Humans , Immunoenzyme Techniques , Male , Neoplasm Proteins/analysis , Parotid Neoplasms/chemistry , Parotid Neoplasms/radiotherapy , Parotid Neoplasms/surgery , Radiotherapy, Adjuvant , Thoracic Neoplasms/chemistry , Thoracic Neoplasms/surgery , Tomography, X-Ray Computed
14.
Mod Pathol ; 13(4): 466-70, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10786816

ABSTRACT

The majority of ovarian sex cord tumors with annular tubules (SCTAT) are benign neoplasms that arise sporadically. In patients who have Peutz-Jeghers syndrome (PJS), ovarian SCTAT is often an incidental finding. Malignant behavior in SCTAT has heretofore been reported only in sporadic cases. We report a case of bilateral, malignant SCTAT developing in a 47-year-old woman who had PJS, originally diagnosed as adenocarcinoma on cervicovaginal cytology. Cervicovaginal and peritoneal fluid cytologic preparations were characterized by pseudopapillary clusters and three-dimensional tubes of tumor cells with scanty cytoplasm and high nuclear: cytoplasmic ratio. Examination of surgical resection specimens revealed bilateral, solid ovarian tumors composed of simple and complex annular tubules with hyaline cores, typical of SCTAT. Tumor emboli were present within salpingeal lymphovascular spaces and in both right and left pelvic lymph nodes. Flow cytometry of tumor cells demonstrated a diploid phenotype. This case represents the first documented example of bilateral, malignant SCTAT arising in a patient who had PJS, presenting with an atypical cervicovaginal smear.


Subject(s)
Ovarian Neoplasms/pathology , Peutz-Jeghers Syndrome/complications , Sex Cord-Gonadal Stromal Tumors/pathology , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/complications , Sex Cord-Gonadal Stromal Tumors/complications , Vaginal Smears
15.
Cancer ; 88(6): 1378-83, 2000 Mar 15.
Article in English | MEDLINE | ID: mdl-10717620

ABSTRACT

BACKGROUND: The FHIT gene, located at human chromosome 3p14.2, frequently is deleted in a number of human tumors, including breast carcinoma. Its protein product (Fhit) is presumed to have tumor suppressor function. Loss of expression of a tumor suppressor gene is an important step in tumor progression from premalignant, to in situ, to invasive carcinoma. METHODS: In the current study, Fhit expression was examined in invasive carcinomas and in epithelial lesions representing stages of carcinoma progression in 50 mastectomy specimens using immunohistochemical methods. RESULTS: Normal ductal and lobular epithelium consistently and strongly expressed Fhit. A complete loss of or a significant reduction in Fhit expression was observed in 72% of breast carcinomas. A statistically significant, negative correlation in Fhit expression among the stages of disease progression in Fhit negative breast carcinomas was observed (normal epithelium > hyperplasia > atypical hyperplasia and carcinoma in situ > invasive carcinoma), whereas no loss of Fhit expression in precursor lesions was observed in Fhit positive tumors. CONCLUSIONS: These observations are consistent with the observed role of FHIT as a tumor suppressor gene in the pathogenesis of specific subsets of carcinomas.


Subject(s)
Acid Anhydride Hydrolases/genetics , Breast Neoplasms/pathology , Carcinoma/pathology , Neoplasm Proteins/genetics , Proteins/genetics , Breast/pathology , Breast Neoplasms/genetics , Carcinoma/genetics , Carcinoma in Situ/genetics , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/genetics , Carcinoma, Lobular/pathology , Chi-Square Distribution , Chromosomes, Human, Pair 13/genetics , Cohort Studies , Disease Progression , Epithelium/pathology , Female , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor/genetics , Humans , Hyperplasia , Immunohistochemistry , Mastectomy , Neoplasm Invasiveness , Neoplasm Staging , Precancerous Conditions/genetics
16.
J Perinatol ; 19(3): 244-7, 1999.
Article in English | MEDLINE | ID: mdl-10685231

ABSTRACT

Asymptomatic intraplacental choriocarcinoma is a rare event with only a few case reports in the literature. The recognition of such a lesion on routine placental examination is important and prompts rapid clinical evaluation for identifying residual and/or metastatic disease followed by institution of chemotherapy. Failure to recognize such a lesion on gross inspection of the placenta can result in disseminated disease, which can be lethal. The following report describes the placental findings and clinical outcome in a recent case with a review of the relevant literature.


Subject(s)
Choriocarcinoma/pathology , Placenta Diseases/pathology , Pregnancy Complications, Neoplastic/pathology , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chorionic Gonadotropin/blood , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Pregnancy
17.
J Cutan Pathol ; 24(3): 193-6, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9085157

ABSTRACT

A 91-year-old man presented with a 9.0 x 7.0 cm exophytic mass on the dorsum of the right foot, surrounded by a scaling hyperkeratotic plaque-like lesion that had been present for many years. He had similar long-standing hyperkeratotic plaque-like lesions on both legs. Histopathologic examination of the exophytic mass revealed a well-differentiated squamous cell carcinoma surrounded by an eccrine syringofibroadenoma (ESFA). Histochemistry, immunohistochemistry and electron microscopy support this diagnosis. To our knowledge, this is the only reported case of ESFA being intimately associated with a malignant neoplasm.


Subject(s)
Adenoma, Sweat Gland/pathology , Carcinoma, Squamous Cell/pathology , Fibroadenoma/pathology , Foot Diseases/pathology , Neoplasms, Multiple Primary/pathology , Sweat Gland Neoplasms/pathology , Adenoma, Sweat Gland/ultrastructure , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/ultrastructure , Fibroadenoma/ultrastructure , Humans , Male , Neoplasms, Multiple Primary/ultrastructure , Sweat Gland Neoplasms/ultrastructure
18.
J Postgrad Med ; 38(3): 145-7, 1992.
Article in English | MEDLINE | ID: mdl-1303421

ABSTRACT

The rarity of adrenocortical carcinoma prompted us to report a case who came with a history of swelling in the left flank associated with pain, weakness and loss of appetite. Ultrasonography revealed a left retroperitoneal mass which was removed by radical surgery along with the left kidney and spleen. On histopathological examination, a diagnosis of adrenocortical carcinoma was made. (Hough criteria score 2.97). The cells of the tumor were arranged in closely packed columns and cords supported by fibrovascular stroma. There was no evidence of metastasis.


Subject(s)
Adrenal Rest Tumor/surgery , Retroperitoneal Neoplasms/surgery , Adrenal Rest Tumor/diagnostic imaging , Humans , Male , Middle Aged , Retroperitoneal Neoplasms/diagnostic imaging , Ultrasonography
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