Carcinoma of the fallopian tube: Results of a multi-institutional retrospective analysis of 127 patients with evaluation of staging and prognostic factors.

The aim of this study was to determine the impact of prognostic factors in primary fallopian tube carcinoma (PFTC). All cases of PFTC diagnosed between 1990 and 2010 were retrieved from the files of 6 academic centers. The cases were staged according to a modification of the International Federation of Obstetrics and Gynecology staging system proposed by Alvarado-Cabrero et al (Gynecol Oncol 1999; 72: 367-379). One hundred twenty-seven PFTC cases were identified. The mean age of the patients was 64.2 years. Stage distribution was as follows: 72 (57%), stage I; 19 (15%), stage II; 28 (22%), stage III; and 8 (6.2%), stage IV. Depth of infiltration of the tubal wall was an independent prognostic factor in stage I cases (P < .001). Carcinomas located in the fimbriated end even without invasion had a worse prognosis than did carcinomas involving the tubal portion of the organ. The presence of vascular space invasion correlated with the depth of tubal wall invasion (P = .001) and the presence of lymph node metastases (P = .003). Tumor grade significantly correlated with survival (P < .0001), but histologic type was of marginal significance and only if it was grouped as nonserous/non-clear cell vs serous/clear cell (P = .04). The depth of invasion of the tubal wall and the presence of carcinoma in the fimbriated end even without invasion are important prognostic indicators. The modified International Federation of Obstetrics and Gynecology staging system should be used on a routine basis in all carcinomas of the fallopian tube.

Enterovesical fistula caused by non-Hodgkin's lymphoma of the ileum: report of a case.

We herein present a rare case of enterovesical fistula caused by ileal non-Hodgkin's lymphoma. A 75-year-old Japanese male presented with macrohematuria at Kosei General Hospital in December 2010. An egg-sized mass was palpable in his right lower abdominal region, and computed tomography (CT) revealed that the ileal tumor had invaded the right posterior wall of the urinary bladder (UB). A histopathological examination of a CT-guided needle biopsy specimen revealed diffuse large B-cell lymphoma involving the ileum and the UB. Thereafter, fecaluria appeared. A transurethral catheter was put in place, and there were no symptoms of cystitis. The patient received chemotherapy for the lymphoma, which produced a partial response. However, the fecaluria continued, and an examination of the small intestine with contrast revealed a thick and irregular wall of the ileum and a fistula between the ileum and UB. A partial resection of the ileum and a partial cystectomy were carried out in April 2011. The surgical specimen demonstrated two tumors 5 cm apart in the ileum, measuring 4.5 × 7 and 4 × 3 cm in size. The proximal tumor had directly invaded the UB and formed an ileovesical fistula. The patient made a good recovery and was doing well 5 months after the surgery without any evidence of recurrence.

[A case of solitary bone cyst in the skull increasing in size after trivial head injury].

A 12-year-old boy had been known to have a small swelling in the left high vertex for several years. After a trivial head hit to the site of the swelling, the swelling enlarged gradually. A bone window CT scan showed a lesion having bubble-like lytic change in the left parietal bone. Similar changes, but small, were able to be pointed out in a CT scan taken seven years previously. In the following 13 months CT scans eventually revealed sequential increases to 3.5 cm in diameter. Surgical exploratory resection of the mass was performed. Intraoperatively, partial destruction of the outer skull table and a simple cyst with serous yellowish brown colored fluid were identified. There was no finding adherent to the diploic structure. The bone defect after excision was reconstructed by using a titanium plate. The patient was followed up for 2 years after the surgery. Bone window CT showed bony development of normal appearance. Histological examination showed the cyst wall consisted of fibrous connective tissue but there were neither epithelial nor endothelial cells. The histopathological diagnosis of SBC was most likely. SBC is relatively common in long bones, but rarely in flat bones. Only several cases of the SBC of cranial bone have been reported. Although a craniectomy for total excision followed by cranioplasty by resin was common, in cases of children, cyst removal with titanium plate application would be an alterative. SBC increasing in size after head injury is extremely rare, but clinicians may need to be aware of cystic skull bone tumors increasing in size after head injury.

Next-Generation Sequencing for Non-Ampullary Duodenal Carcinoma Suggesting the Existence of an Adenoma-Carcinoma Sequence.

Duodenal tumors with a sporadic adenoma-carcinoma sequence are extremely rare. For such clinically suspected cases without a specific family history, performing a comprehensive gene search is important to understand the germline mutation background. We present a 68-year-old woman without a genetic or familial history of familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, or Lynch syndrome who presented to Kosei Hospital, Japan, with exertional dyspnea induced by abdominal pain lasting 3 weeks. A duodenal tumor was suspected by contrast-enhanced computed tomography. Esophagogastroduodenoscopy showed a lesion accompanied by a white microprotuberance on the descending part of the duodenum opposite the papilla, with a giant ulcerative lesion at the center of the white lesion. Biopsy revealed a low-grade adenoma, high-grade adenoma, and adenocarcinoma. Immunohistochemical analysis of the adenoma and adenocarcinoma showed Ki-67, p53, cytokeratin 20, caudal-type homeobox 2, and carcinoembryonic antigen positivity and cytokeratin 7 negativity. The findings suggested the presence of an adenoma-adenocarcinoma sequence in duodenal carcinoma. However, in the mutational analysis using next-generation sequencing, c.4348C>T (p.Arg1450Ter) mutation in APC was detected in all normal mucosal, adenoma, and carcinoma tissues. This mutation is common in FAP patients. Even if the presence of an adenoma-adenocarcinoma sequence in duodenal carcinoma is suggested in cases without a familial FAP history, as in this case, genetic analysis may reveal FAP. Thus, performing a comprehensive genetic analysis of duodenal carcinoma patients with a possible adenoma-carcinoma sequence is necessary to explore their genetic background.

Immunohistochemical localization of heme oxygenase-1 and bilirubin/biopyrrin of heme metabolites as antioxidants in human placenta with preeclampsia.

Introduction: We performed an immunohistochemical investigation of the localization of Heme oxygenase(HO-1) and bilirubin(BR)/biopyrrin(BPn) to elucidate whether a response to oxidative stress is generated in the human placenta.Methods: Placentas from nine patients with preeclampsia(PE) and seven controls were investigated.Results: For HO-1 and BR/BPn expressions, a higher number of positive cells were observed in the PE group than in the control group.Conclusions: The degree of these expressions tended to relate to the onset of PE. This suggests that the heme catabolic pathway induced by oxidative stress plays an important role in the pathophysiology of PE.

Ascending Colon Schwannoma Surgically Treated after Accurate Preoperative Diagnosis.

Colorectal schwannomas are rare and usually benign gastrointestinal mesenchymal tumors. However, these tumors are often overtreated, possibly owing to misleading malignant potential. To our knowledge, there have been no previous reports of ascending colon schwannoma preoperatively diagnosed as benign schwannoma. Herein, we report a case of ascending colon schwannoma accurately diagnosed by endoscopic biopsy and successfully treated by wedge resection. The patient was a 76-year-old woman with complaints of bloody stool. She had no relevant past medical history. Radiological findings revealed a protruded mass in the ascending colon, and colonoscopy revealed a submucosal tumor measuring approximately 3 cm in diameter with a reddish and uneven surface. Histological and immunohistochemical analysis for vimentin and S100 protein of the specimen obtained by endoscopic biopsy confirmed the diagnosis of schwannoma. Thus, we performed laparoscopy-assisted endoscopic full-thickness resection of the ascending colon wall, as appropriate for a benign soft tissue tumor. The postoperative course has been uneventful for 2 years. This case demonstrates that colonic schwannoma can be successfully treated with adequate resection if an accurate preoperative diagnosis is made, thereby avoiding overtreatment, such as surgery for colorectal tumor including lymph node dissection. Preoperatively diagnosed schwannomas should be treated by wedge resection, with postoperative pathological findings confirming the presence or absence of malignancy. Additional resection should be considered for very rare cases of coexisting malignant tissue.

Mesenchymal to epithelial transition in the human ovarian surface epithelium focusing on inclusion cysts.

Most ovarian cancers arise from the mesothelial surface lining of the ovaries or from invaginations of this lining into the superficial ovarian cortex that form cortical inclusion cysts. Thus, these cysts are thought to be precursor lesions of ovarian carcinoma. Epithelial-mesenchymal transition, which is a transcriptional program for inducing maintenance of the mesenchymal phenotype, acts in tumor progression and metastasis. Little is known about the mechanisms involved in mesenchymal-epithelial transition (MET). We aimed to characterize the human ovarian surface epithelium (OSE) and inclusion cysts by immunohistochemical analysis to examine whether MET occurs during inclusion cyst formation in the OSE. We used specimens from 9 endometrial cancer patients who had undergone hysterectomy and bilateral salpingo-oophorectomy. Immunohistochemical analysis was performed in 10 normal ovaries containing 92 inclusion cysts and in 4 normal tubes to examine the expression of antigen markers including calretinin, podoplanin, D2-40, thrombomodulin, HBME-1, vimentin, EMA, WT1, CA125, MOC31, TAG-72, Ber-EP4 and E-cadherin. The positive staining rates for mesothelial markers in normal OSE were 100% (10/10) for calretinin, 80% (8/10) for podoplanin, 80% (8/10) for D2-40, 70% (7/10) for thrombomodulin, 100% (10/10) for HBME-1, 100% (10/10) for vimentin. The positive staining rates for epithelial markers in tubal epithelium were 100% (4/4) for HBME-1, 100% (4/4) for vimentin, 100% (4/4) for EMA, 75% (3/4) for TAG-72, 100% (4/4) for Ber-EP4. Inclusion cysts showed positive staining for both markers with an incidence of 51% (47/92) for HBME-1, 44% (41/92) for vimentin, 65% (60/92) for TAG-72, 88% (81/92) for Ber-EP4. The OSE showed the characteristics of both mesenchymal and epithelium cells. In contrast, inclusion cysts gained epithelial characteristics, but lost mesenchymal characteristics. These findings support that MET occurs during the inclusion cyst formation from OSE.

Establishment of an immortalized human extravillous trophoblast cell line by retroviral infection of E6/E7/hTERT and its transcriptional profile during hypoxia and reoxygenation.

Investigation into the function of human trophoblasts has been largely restricted by a lack of suitable cell models. We aimed to produce normal human trophoblast cell lines with a long lifespan and to provide an ideal in vitro cell model. Primary human trophoblast cells were derived from a placenta that had undergone elective abortion at the 7th week of gestation. The cells were immortalized by infection with retroviral expression vectors containing the type 16 human papillomaviruses E6 and E7 in combination with human telomerase reverse transcriptase (hTERT). Characterization of the cell line was performed by immunocytochemistry using a panel of antibodies, Western blotting, real-time RT-PCR, an invasion assay, gelatin zymography, karyotype analysis and a nude mouse assay. Gene expression profiles under hypoxia (1% O2, 1 h) and subsequent reoxygenation (20% O2, 6 h) were analyzed using cDNA microarray. Immunocytochemistry revealed an extravillous trophoblastic phenotype by positive staining for hCGbeta, cytokeratin 7, HLA-G and CD9. A transwell insert invasion assay showed the invasiveness of this cell line and gelatin zymography detected the secretion of MMP-2 and MMP-9. Karyotype analysis exhibited an almost normal chromosomal number which ranged from 46 to 48 and the cells showed no tumorigenecity in a nude mouse assay. Forty-three genes showing reversible up- or down-regulation during hypoxia were detected using an oligonucleotide array. This newly immortalized cell line, HChEpC1b, is a useful model for the study of extravillous trophoblast function.

The expression of NeuroD and mASH1 in the gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors are uncommon and their tumor biology has not been well elucidated to date. Currently the WHO classification is widely used for the diagnosis and distinction of this tumor entity, which is sometimes cumbersome. Although neuroendocrine tumor markers do exist (ie chromograninA, synaptopyhsin, etc), sensitive and specific markers that accurately predict tumor growth and tumor behavior are still absent. In the present study, we assessed the expression of transcription factors (NeuroD and mASH1) essential for the normal fetal neuronal development in 33 gastroenteropancreatic neuroendocrine tumor patients (12 well-differentiated neuroendocrine tumors, 7 well-differentiated neuroendocrine carcinomas, and 14 poorly differentiated neuroendocrine carcinomas). NeuroD was less expressed in poorly differentiated neuroendocrine carcinoma (small-cell type) compared to well-differentiated neuroendocrine tumor (carcinoid) by reverse transcription-polymerase chain reaction. Immunohistochemical staining revealed that mASH1 was highly (sensitivity of 71%) and specifically (specificity of 95%) expressed in poorly differentiated neuroendocrine carcinoma. High NeuroD expression was seen in all well-differentiated neuroendocrine carcinoma and tumor (carcinoid) patients. Low NeuroD expression was seen in 36% (5 of 14) of poorly differentiated neuroendocrine carcinoma patients, which was associated with significant shorter overall survival. The expression pattern of these transcription factors may represent the biological and pathophysiological difference of gastroenteropancreatic neuroendocrine tumors and may become a new marker for the distinction of gastroenteropancreatic neuroendocrine tumors.

Association of extracellular matrix metalloproteinase inducer in endometrial carcinoma with patient outcomes and clinicopathogenesis using monoclonal antibody 12C3.

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin superfamily of adhesion molecules and has a role in the activation of several matrix metalloproteinases (MMPs). We evaluated whether EMMPRIN expression is related to tumor progression and patient outcome in human endometrial carcinoma. Paraffin-embedded surgical tissue samples from 112 patients with endometrial carcinoma were stained with anti-EMMPRIN antibody (monoclonal antibody 12C3:MoAb 12C3) for immunohistochemical analysis. EMMPRIN protein was expressed in cancerous lesions with the incidence of 97.3% (109 of 112 cases), but not in normal lesions. The scores determined by the combination of intensity and pattern of EMMPRIN staining in cancer cells correlated significantly with various histopathological risk factors: advanced stage, P=0.001; poorly differentiated carcinoma, P<0.001; lymph node metastasis, P=0.002; and lymphatic vessel infiltration, P=0.027. More importantly, recurrence-free survival was shortened in patients with higher EMMPRIN scores (HR, 3.08; 95% CI, 1.32-7.19; P=0.01). These results suggest that measurement of EMMPRIN expression with simple immunohistochemical staining may enhance the understanding of the pathophysiology of endometrial carcinoma.

Increased synthesis of indoleamine-2,3-dioxygenase protein is positively associated with impaired survival in patients with serous-type, but not with other types of, ovarian cancer.

We previously reported that indoleamine-2,3-dioxygenase (IDO) is associated with paclitaxel resistance and that IDO serves as a marker of poor prognosis in ovarian serous adenocarcinomas (SA). In this study, to explore the role of IDO in the development of various histological types of ovarian cancer, we further examined IDO expression not only in SA but also in other types of ovarian cancers. Expression of IDO protein was analyzed by immunohistochemistry for a total of 122 ovarian cancers including 40 SA, 67 clear cell adenocarcinomas (CCA), and 15 endometrioid adenocarcinomas (EA) with informed consent. Among these cases, there were 11 CCA accompanied with endometriosis and 60 cases with lymph node metastasis. We classified the samples into four categories by IDO staining pattern. IDO staining was positive in 57.5% of SA, 49.2% of CCA, and 73.3% of EA, respectively. The Kaplan-Meier survival curve showed a clear relationship between staining score and overall survival for patients with advanced (stages III and IV) SA (n=33) who underwent optimal surgery and paclitaxel-carboplatin (TC) chemotherapy as a first-line regimen. There was no association between IDO staining score and overall survival in the CCA cases. Eight of 11 cases (72.7%) of CCA accompanied by endometriosis presented identical staining patterns of IDO between CCA and endometriosis. In 43 of 60 cases (71.6%) with lymph node metastasis, the staining patterns of IDO showed a correspondence between the primary lesion and metastatic site. These results suggested that the increased synthesis of IDO protein was positively associated with impaired survival only in the serous type of ovarian cancer.

Clinical and genetic analysis of recurrent adult-type granulosa cell tumor of the ovary: Persistent preservation of heterozygous c.402C>G FOXL2 mutation.

BACKGROUND: Adult-type granulosa cell tumors of the ovary (aGCTs) are rare tumors that represent 2-5% of ovarian malignancies. The prognosis of this tumor is favorable, and it is characterized by slow progression. 10-30% of these tumors recur after 4-7 years of the primary surgery and the 5-year survival rate from the first recurrence is 55%, for the incompletely resected patients. At this time, complete resection is the only prognostic factor for better outcome, and establishing a novel strategy for identification and/or treatment of recurrent tumors is crucial. After the discovery of heterozygous c.402C>G FOXL2 mutations in 97% of cases of aGCT, much effort has been made to find the role of the mutation on the pathogenesis of aGCT, however, little is known about the role of the mutation in disease progression. METHODS: We analyzed the clinical data of 56 aGCT patients to find a marker of recurrence. In particular, we compared the FOXL2 status in 5 matched primary and recurrent samples by immunohistochemistry, and TaqMan allelic discrimination assay to address the role of FOXL2 in potential mechanisms of recurrence. RESULTS: The clinical data analysis was consistent with complete resection as an indicator of disease eradication, though the sample size was limited. The genetic analysis showed all the samples, including recurrent tumor samples up to 14 years after the primary surgery, expressed heterozygous c.402C>G FOXL2 mutation and the FOXL2 protein expression. CONCLUSION: This report describes the preservation of heterozygous c.402C>G FOXL2 mutation in recurrent aGCTs. This finding adds further credence to the concept that the c.402C>G FOXL2 mutation is oncogenic and integral to this disease.

Sonic Hedgehog-Gli1 signaling pathway might become an effective therapeutic target in gastrointestinal neuroendocrine carcinomas.

Gastrointestinal neuroendocrine carcinomas (NECs) are extremely aggressive and poorly prognostic. We showed previously that human achaete-scute homologue gene 1 (hASH1), a basic helix-loop-helix transcription factor regulated by Notch, was aberrantly expressed in NECs. To date, no effective therapeutic strategies for NECs have been investigated. Notch, Wnt and Hedgehog (Hh) signalings are important for stem cell self-renewal and carcinogenesis in the gastrointestinal epithelium. In this study, we showed that Hh signaling was clearly upregulated in NECs in Gli1-dependent manner. Specific therapeutic effects of cyclopamine on NECs were also demonstrated. RT-PCR showed that among eight frozen samples (three NECs, one carcinoid tumor, three adenocarcinomas and one normal mucosa), the band intensities of Gli1 were the strongest in NECs, moderately strong in a carcinoid tumor, very weak in adenocarcinomas and undetectable in a normal mucosa. In real-time RT-PCR, the expression levels of Gli1 in NECs were 108.4, 28.6 and 16.3 times higher than that in an adenocarcinoma. In immunohistochemistry using 25 paraffin-embedded tissues, all twelve NECs and three of six carcinoid tumors showed positive stainings for Gli1, whereas six of seven adenocarcinomas were negative. In vitro, RT-PCR showed that NEC cell lines expressed Gli1 mRNA significantly. Administration of cyclopamine suppressed cell proliferation and invasion, and induced apoptosis in NECs. In cyclopamine-treated NECs, downregulation of Gli1, Ptch1, Snail and hASH1, and upregulation of E-cadherin were demonstrated at mRNA levels. Such effects were not observed in a Gli1-negative colonic adenocarcinoma cell line or in control alkaloid-treated NECs. Hh signaling may play a crucial role in the pathophysiology of NECs. Blockade of Hh pathway using cyclopamine or its synthetic derivatives might open an effective therapeutic strategy to NECs, not only by suppressing tumor viability but also by altering tumor cell nature.

Aberrant expression of human achaete-scute homologue gene 1 in the gastrointestinal neuroendocrine carcinomas.

PURPOSE: Gastrointestinal neuroendocrine carcinoma (NEC) is extremely aggressive, but its pathophysiologic features remain poorly understood. There have been no biologically specific markers for this disease. In this study, distinctive up-regulation of human achaete-scute homologue 1 (hASH1) in gastrointestinal NECs was clarified. EXPERIMENTAL DESIGN: Expression of hASH1 in NECs (n=10), carcinoid tumors (n = 10), other tumors (10 adenocarcinomas, 2 squamous cell carcinomas and 1 malignant lymphoma), and the corresponding normal mucosa were investigated by in situ hybridization, reverse transcription-PCR (RT-PCR), real-time RT-PCR, and immunohistochemistry. RESULTS: By in situ hybridization, mild to intense signals of hASH1 mRNA were detected in 9 of 10 NECs, but not in other tumors or normal mucosa, except for focally weak signals in one carcinoid tumor. RT-PCR showed strong expression of hASH1 in a small cell NEC, followed by a moderately differentiated NEC, and a carcinoid tumor, whereas it is undetectable in adenocarcinomas or normal mucosa. By real-time RT-PCR, the amounts of hASH1 mRNA in a small cell NEC were 16,600 times higher than those in adenocarcinomas and 110 times higher than those in a carcinoid tumor. Immunohistochemically, mammalian homologue of hASH1 was positive in 7 of 10 NECs but was negative in the other tumors. Pan-endocrine markers chromogranin A and synaptophysin were positive in almost all carcinoid tumors, in 4 and 7 of the 10 NECs, respectively. CONCLUSIONS: These findings revealed that hASH1 is distinctly up-regulated in gastrointestinal NECs. hASH1 may be used as a more sensitive and specific marker than conventional pan-endocrine markers for clinical diagnosis of gastrointestinal NECs.

Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells.

PURPOSE: We aimed to find key molecules associated with chemoresistance in ovarian cancer using gene expression profiling as a screening tool. EXPERIMENTAL DESIGN: Using two newly established paclitaxel-resistant ovarian cancer cell lines from an original paclitaxel-sensitive cell line and four supersensitive and four refractory surgical ovarian cancer specimens from paclitaxel-based chemotherapy, molecules associated with chemoresistance were screened with gene expression profiling arrays containing 39,000 genes. We further analyzed 44 genes that showed significantly different expressions between paclitaxel-sensitive samples and paclitaxel-resistant samples with permutation tests, which were common in cell lines and patients' tumors. RESULTS: Eight of these genes showed reproducible results with real-time reverse transcription-PCR, of which indoleamine 2,3-dioxygenase gene expression was the most prominent and consistent. Moreover, by immunohistochemical analysis using a total of 24 serous-type ovarian cancer surgical specimens (stage III, n = 21; stage IV, n = 7), excluding samples used for GeneChip analysis, the Kaplan-Meier survival curve showed a clear relationship between indoleamine 2,3-dioxygenase staining patterns and overall survival (log-rank test, P = 0.0001). All patients classified as negative survived without relapse. The 50% survival of patients classified as sporadic, focal, and diffuse was 41, 17, and 11 months, respectively. CONCLUSION: The indoleamine 2,3-dioxygenase screened with the GeneChip was positively associated with paclitaxel resistance and with impaired survival in patients with serous-type ovarian cancer.

FGF7-like gene is associated with pericentric inversion of chromosome 9, and FGF7 is involved in the development of ovarian cancer.

Pericentric inversion of chromosome 9 is a common chromosomal aberration that may be involved in the pathogenesis of several types of cancer. Screening for structural balanced chromosomal aberrations in 58 patients with ovarian carcinoma found a patient with inv(9)(p11;q13) who had repeated spontaneous abortions. To define the breakpoint at the 9p11 region, the human 9p11-specific CEPH-YAC library was first screened with fluorescence in situ hybridization (FISH) analysis, resulting in isolation of the YAC clones 961d9 and 954b9 spanning the breakpoint. Next, screening with FISH analysis of the cosmid library constructed from 961D9 isolated 3 cosmid clones that included the breakpoint. DNA sequence analysis showed that the cosmid clones spanned the 57.7-kb sequence, which contained the FGF7 [keratinocyte growth factor (KGF)]-like gene including exons 2 and 3. FISH analysis showed that the 57.7-kb sequence was duplicated from the 9p11 region to the 9q13 region on the aberrant chromosome 9. Southern blot analysis showed multiple FGF7-like genes in the 9p11 region which were also duplicated to the 9q13 region on the aberrant chromosome 9. Because the FGF7-like genes are located at 9p11 and 9q13, our results are consistent with the hypothesis that the FGF7-like genes at 9p11 and 9p13 initiate the pericentric inversion of chromosome 9. Analysis of surgical specimens of ovarian cancer with the reverse transcription-polymerase chain reaction and immunohistochemical staining showed overexpression of the FGF7 gene in 4 of 9 stage I or II cases and in 10 of 11 stage III or IV cases. These findings suggest that FGF7 plays a significant role in the development of ovarian cancer.

Frequent apoptosis in placental villi from pregnancies complicated with intrauterine growth restriction and without maternal symptoms.

The objective of this study was to examine the incidence of apoptosis in placentas of intrauterine growth restriction (IUGR) without maternal disease. We focused on cases of IUGR with both unknown causes and no maternal complications. In addition, apoptosis of IUGR placentas was correlated with the expression of proteins involved in apoptosis and cell turnover. The term placentas were obtained from 16 normal and 10 IUGR pregnancies without maternal symptoms. We analyzed the localization of apoptosis and counted >2000 nuclei by TUNEL assay and transmission electron microscopy in placentas from normal and IUGR cases. We found the incidence of apoptosis to be significantly higher in placentas with IUGR (2.98%) than in normal placentas (1.46%) by TUNEL assay (p=0.03). In addition, immunohistochemical analysis was performed to examine the expression of proteins related to apoptosis and general cell turnover, including the active form of caspase-3, Bax, p53, and Ki-67. Expression of the active form of caspase-3 was significantly higher in IUGR than in a normal pregnancy (p=0.03). These results suggest that enhanced execution of apoptosis through caspase-3 may play a role in IUGR without maternal symptoms.

Ultrasound Demonstration of Mammographically Detected Microcalcifications in Patients with Ductal Carcinoma in situ of the Breast.

BACKGROUND: Breast microcalcifications are difficult to depict by ultrasound (US). However, recent advances in US equipment and the refinement of breast imaging techniques have improved the detection and characterization of small breast lesions. The present study attempts to determine whether US examination is able to demonstrate nonpalpable breast lesions associated with mammographically detected microcalcifications without mass density or distortion, and to evaluate the clinical reliability of US-guided procedures, especially in cases of ductal carcinoma in situ(DCIS)of the breast. METHODS: The subjects consisted of 73 patients with breast cancer diagnosed preoperatively as DCIS by stereotactic core needle biopsies, all of whom had microcalcifications without other abnormalities on mammography. The radiological appearance and size of the clustered microcalcifications were evaluated. US examinations were performed preoperatively, and the detection rates were assessed. Sonographically detected lesions underwent US-guided wire localization followed by surgical excision. RESULTS: The lesions associated with microcalcifications were identified sonographically in 54 of 73 cases (74%), and the pathological examination revealed breast cancer in all of the corresponding specimens. Lesions with linear-branching shape, segmental-linear distribution and category-5 calcifications on mammography had a high level of visibility on US. The US visible cases had a larger size of calcified area on mammography when compared with US invisible cases. Pathologically, the lesions were more frequently seen on US in cases with minimally invasive cancer or with comedo type DCIS. CONCLUSIONS: US examination is an effective method for identifying and localizing breast microcalcifications, and can be used as an alternative to stereotactic localization in selected patients with early breast cancer.

Establishment and characterization of a cell line designated Nur-1 derived from human endometrioid adenocarcinoma of uterine corps.

A new cell line designated Nur-1 has been established from human endometrioid adenocarcinoma, Grade 1, pT1a, PN1 (3/24), Stage IIIc (International Federation of Gynecology and Obstetrics/Union for International Cancer Control (FIGO/UICC TNM Classification of Malignant Tumours, 7th ed.). Cytological findings of Nur-1 cells reveal anaplastic and pleomorphic features such as anisonucleosis, nucleolar pleomorphism, and piling-up tendency in cellular arrangement. Distribution of the chromosome number is found at the hyperploid range, and the apparent marker chromosome has not been identified. The original tumor and graft of the Nur-1 cell line had a large amount of estrogen receptors and progesterone receptors, as revealed by immunohistochemistry. The cytokeratin pattern of the tumor was positive for cytokeratin-7 and negative for cytokeratin-20. However, a few cells were positive for cytokeratin-20 in the original tumor. Nur-1 cells express mRNA of estrogen receptors and progesterone receptors, cytokeratin-7, and cytokeratin-20 at 105 passages. These findings are consistent with the cytokeratin pattern of endometrial glandular cells. The cells make contact with each other via interdigitation and desmosomes. They possess bundles of microtubules and tonofilaments and many free ribosomes. Some cells have various sizes of phagosomes. The Nur-1 cell line exceeded 102 passages in 5 years, and multiplication of the cells is stable. The modal number of the Nur-1 cell line is 91-92 (56 %). The Nur-1 cells develop well-differentiated adenocarcinoma in tumors sustained in nude mice that resemble the original tumors.

Squamous predominance in mixed-epithelial papillary cystadenomas of borderline malignancy of mullerian type arising in endometriotic cysts: a study of four cases.

Mixed-epithelial papillary cystadenoma of borderline malignancy of mullerian type (MEBMM) is composed of a mixture of mullerian epithelial types, such as mucinous, serous, endometrioid, and squamous. Four cases of MEBMM with squamous overgrowth (MEBMMSO) were reviewed. The patients' median age was 56 years, and all cases were unilateral. The clinical stages were Ia (two cases), Ic (one case), and IV based on the presence of tumor cells in pleural fluid (one case). No recurrence was seen in three of the cases. In one of those three cases, there was no recurrence after undergoing surgery only; in the other two of those three cases, there was no recurrence after undergoing surgery and receiving postoperative chemotherapy. In the single case that was at stage IV at initial presentation, a recurrent MEBMMSO nodule was found at a second look 17 months after the initial surgery. In terms of gross findings, all of the tumors were cystic with intracystic papillary fronds. In addition, old endometriotic lesions lined the cysts. The tumors were mainly composed of a proliferation of squamous-type epithelium, with minor foci containing a mixture of other mullerian-type epithelia, especially mucinous. Intraepithelial infiltration by neutrophilic leukocytes was prominent. The differential diagnosis of MEBMMSO includes proliferating Brenner tumors.