bluuebunny/crossref_metadata_2025 huggingface dataset:
Syndecan‐1 expression in thyroid carcinoma: stromal expression followed by epithelial expression is significantly correlated with dedifferentiation
Authors: Ito Y , Yoshida H , Nakano K , Takamura Y , Miya A , Kobayashi K , Yokozawa T , Matsuzuka F , Matsuura N , Kuma K , Miyauchi A
Published: December 2004

Aim:  To investigate the expression of syndecan‐1 in thyroid neoplasia. Syndecan‐1 is a proteoglycan regulating cell adhesion. Previous studies have demonstrated that decreased expression of syndecan‐1 is linked to malignant progression.

Methods and results:  Syndecan‐1 expression in thyroid neoplasia was studied immunohistochemically. Syndecan‐1 was expressed in stromal cells as well as neoplastic epithelial cells. Stromal syndecan‐1 expression was observed more frequently in papillary carcinomas larger than 10 mm in size than in microcarcinomas and in widely invasive than in minimally invasive follicular carcinomas. Furthermore, poorly differentiated carcinomas showed this phenomenon more than well‐differentiated carcinomas, but the expression in undifferentiated carcinomas was similar to that of poorly differentiated carcinomas. Epithelial syndecan‐1 expression was more frequently observed in anaplastic (undifferentiated) carcinomas than in papillary and follicular carcinomas. No significant difference in epithelial expression was found between well and poorly differentiated carcinomas, but undifferentiated carcinomas expressed epithelial syndecan‐1 more frequently than did poorly differentiated carcinomas.

Conclusions:  These results are in contrast to those previously reported for carcinomas at other sites. It is suggested that the role of syndecan‐1 in thyroid carcinomas might be unique. Stromal syndecan‐1 expression followed by its epithelial expression is significantly related to progression, including dedifferentiation of thyroid carcinoma.
A comparative histological and morphometric study of vascular changes in idiopathic portal hypertension and alcoholic fibrosis/cirrhosis
Authors: Tsuneyama K , Ohba K , Zen Y , Sato Y , Niwa H , Minato H , Nakanuma Y
Published: December 2004

Aim:  To examine the pathological changes of hepatic arteries in idiopathic portal hypertension (IPH) which is characterized by the obliteration of the intrahepatic portal vein branches and presinusoidal portal hypertension.

Methods and results:  Liver specimens (biopsied or surgically resected) from 20 patients with IPH, 20 patients with alcoholic fibrosis/cirrhosis (AF/C) and 20 histologically normal livers were used. The vascular lumina of arterial and venous vessels in portal tracts were morphometrically evaluated by an image analysis system. The ratio of portal venous luminal area to portal tract area (portal venous index) of IPH and that of AF/C were significantly reduced compared with normal liver. The portal venous index for IPH was significantly lower than that for AF/C. The ratio of hepatic arterial luminal area to portal tract area for AF/C was significantly higher than that in normal liver; however, that for IPH was similar to normal. The peribiliary vascular plexus was increased in AF/C but not in IPH. In AF/C, the number of mast cells and macrophages known to be the source of angiogenic substances was significantly increased in the portal tract compared with normal liver, while in IPH it was not increased.

Conclusions:  In AF/C, a reduction in portal venous lumen was associated with an increase of hepatic arterial lumen and of angiogenesis‐related cells in portal tracts. However, such compensatory arterial changes were not evident in IPH, and this compensatory failure may be a feature of IPH.
Clinicopathological analysis of 143 primary malignant lymphomas in the small and large intestines based on the new WHO classification
Authors: Kohno S , Ohshima K , Yoneda S , Kodama T , Shirakusa T , Kikuchi M
Published: December 2004

Aim:  To study the clinicopathological and immunohistochemical features of 143 cases of primary small and large intestinal non‐Hodgkin's lymphoma (NHL) in Japanese patients who presented between 1981 and 2000.

Methods and results:  The new World Health Organization (WHO) classification was used to classify NHL. The patients included 109 males and 34 females, with an average age of 54.1 years. Tumour sites were as follows: ileocaecal (n = 51, 35.7%), ileum (n = 29, 20.3%), rectum (n = 13, 9.1%), and duodenum (n = 11, 7.7%). Macroscopically, 124 cases (86.7%) were classified as tumorous type, 12 (8.4%) as diffuse infiltration type (erosion, superficial ulceration), five (3.5%) as polyposis type, and only two cases (1.4%) as ulceration type. Immunohistochemically, 122 lesions (85.3%) were of B‐cell phenotype and 21 lesions (14.7%) were of T‐cell phenotype. According to the WHO classification, of the B‐cell lymphomas, 84 cases (68.9%) were large cell, 16 (13.1%) were Burkitt, 10 (8.2%) were marginal zone B‐cell lymphomas of mucosa‐associated lymphoid tissue (MALT), and seven (5.7%) were mantle cell tumours. Among the T‐cell lymphomas, 15 (71.4%) were of unspecified type, two (9.5%) were natural killer type, two were anaplastic large‐cell lymphomas, one was lymphoblastic, and one was an adult T‐cell leukaemia lymphoma. The survival rate for T‐cell lymphomas was poorer than for B‐cell lymphomas. Among the B‐cell lymphomas, mantle cell lymphoma tended to have a poorer prognosis, whereas MALT lymphomas had a better prognosis than other B‐cell tumour types.

Conclusions:  Our retrospective study of patients with primary malignant lymphomas in the small and large intestines has illustrated the clinical features and outcomes of patients with this disease.
Glomerular crescents predominantly express cadherin–catenin complex in pauci‐immune‐type crescentic glomerulonephritis
Authors: Usui J , Kanemoto K , Tomari S , Shu Y , Yoh K , Mase K , Hirayama A , Hirayama K , Yamagata K , Nagase S , Kobayashi M , Nitta K , Horita S , Koyama A , Nagata M
Published: December 2004

Aims:  To investigate the expression of the cadherin complex in human crescentic glomerulonephritis to elucidate the role of intercellular adherens junction molecules in crescent formation.

Methods and results:  Immunostaining revealed cadherin complexes localized in Bowman's epithelial cells, but not in podocytes, of normal human glomeruli. Eight adult cases with myeloperoxidase anti‐neutrophil cytoplasmic autoantibodies (MPO‐ANCA)‐related (pauci‐immune type) crescentic glomerulonephritis were examined on immunofluorescence microscopy with anti‐pan cadherin, p120 catenin, and β‐catenin antibodies. The specimens provided six cellular crescents, 12 fibrocellular crescents, and four fibrotic crescents. Immunofluorescence was semiquantitatively estimated by the rate of the field of localization within the whole area of the crescent, according to the four‐grade system [(–) − (++)]. All the tested molecules consisting of the cadherin complex were abundantly observed in cytokeratin‐positive epithelial components in crescents, each with an equivalent area of localization. The expression of the cadherin complex was closely associated with that of cytokeratin and both diminished as the crescents developed from cellular to fibrotic.

Conclusions:  The cadherin–catenin complex is a specific marker of Bowman's epithelial cells in human glomeruli. The cellular crescents in pauci‐immune‐type crescentic glomerulonephritis possess adherens junction molecules, indicating a principle parietal epithelial cell phenotype.
Small vessel vasculitis limited to pleuropulmonary manifestations, possibly induced by endotoxin
Authors: Kumasaka T , Mitani K , Izumi H , Miyamoto H , Takahashi K , Fukuchi Y , Suda K
Published: December 2004

Aims:  We investigated a rare case of small vessel vasculitis (SVV) limited to pleuropulmonary manifestations, possibly induced by endotoxin, to determine the activation of immuno‐mediated cells and endothelia in the pleuropulmonary circulation.

Methods and results:  A 44‐year‐old man with a high fever was X‐rayed, revealing bilateral pleural effusion and atelectasis in the chest. His laboratory data were within normal limits except for a high white blood cell count and a high C‐reactive protein level. Autoantibodies including anti‐neutrophil cytoplasmic antibody were negative. Endotoxin was detected in his sera, but repeated cultures of sputa, urine, blood and the pleural effusion were negative for bacteria. Video‐assisted thoracic surgery was performed and lung and parietal pleura specimens were obtained. Histology showed arterioles or small arteries infiltrated by monocytes or neutrophils with fibrinoid necrosis and acute or chronic venulitis. A diagnosis of SVV in the lung and pleura was made. Immunohistochemistry revealed that interleukin (IL)‐1β was expressed in monocytes and vascular cell adhesion molecule (VCAM)‐1 on endothelial cells in the vasculitic lesions in the lung.

Conclusions:  Endotoxin possibly induced the inflammation in this apparently unique case of pleuropulmonary small vessel vasculitis. Immunohistochemistry revealed the expression of IL‐1β and VCAM‐1 which may have caused activation of monocytes and endothelial cells within the vasculitic lesions.
Fibromyxoid areas and immature osteoid are associated with recurrence of primary aneurysmal bone cysts
Authors: De Silva M V C , Raby N , Reid R
Published: December 2004

Aims:  Primary aneurysmal bone cysts have a high recurrence rate following curettage. The aim of this study was to determine clinicopathological features associated with recurrence of aneurysmal bone cysts.

Methods and results:  The clinicopathological features of 86 patients (37 males, 49 females, age range 5–62 years) with aneurysmal bone cysts were reviewed. Recurrence rates following curettage and excision were 32.7% and 5.6%, respectively (P = 0.028). The association of clinicopathological features with recurrence was studied in a subset of 45 patients treated by curettage. The presence of nodular fasciitis‐like fibromyxoid areas [P = 0.033, odds ratio (OR) = 9.17, 95% confidence interval (CI) 1.06, 79.39] and immature osteoid with active osteoblasts (P = 0.041, OR = 3.7, 95% CI 1.03, 13.35) was significantly associated with an increased risk of recurrence. Clinical and radiological features were not associated with recurrence. In a multivariate analysis, the presence of immature osteoid was a better predictor of recurrence than radiological activity (hazard ratio = 3.18, 95% CI 1.04, 9.73, P = 0.043). There was no statistically significant association between radiological activity and histological features.

Conclusions:  Aneurysmal bone cysts with nodular fasciitis‐like fibromyxoid areas and immature osteoid with active osteoblasts are more likely to recur. Mention of these features in histopathology reports will help to identify patients who require closer follow‐up. Lesions that are apparently radiologically inactive may show fibroblastic and osteoblastic proliferation and therefore may recur.
‘Pseudomesotheliomatous’ carcinomas of the pleura: a 10‐year analysis of cases from the Environmental Lung Disease Research Group, Cardiff
Authors: Attanoos R L , Gibbs A R
Published: December 2004

Aims:  To undertake a clinicopathological study of diffuse serosal neoplasms of epithelial histogenesis which clinically and pathologically mimic malignant pleural mesothelioma.

Methods and results:  Over a 10‐year (1990–2000) study period 53 carcinomas mimicking diffuse pleural mesothelioma (‘pseudomesotheliomatous’ carcinoma) were identified. The study group comprised 50 men and three females, age range 33–77 (median 68) years. In 46 (87%) cases there was a history of smoking and in 40 (76%) cases a history of asbestos exposure. Histologically the pleural ‘pseudomesotheliomatous’ carcinomas could be divided into two broad groups: primary pulmonary carcinomas with florid pleurotropic growth (n = 47), of which 34 (70%) were adenocarcinomas; and diffuse carcinomatous involvement of the pleura by metastatic tumour (n = 6). This latter group comprised two transitional cell carcinomas of bladder, one renal (clear) cell carcinoma, one ductal pancreatic adenocarcinoma, one prostatic adenocarcinoma and one squamous cell carcinoma of parotid gland origin. Follow‐up data were available in 35 cases. Regardless of tumour type, survival was poor (median 8 months) and comparable to diffuse pleural mesothelioma.

Conclusions:  Pleural ‘pseudomesotheliomatous’ carcinomas are uncommon (comprising 6% of referrals), pathologically heterogeneous tumours with poor prognosis. Tissue diagnosis should be obtained in all cases of suspected diffuse pleural neoplasia. By light microscopy and immunophenotype many of the tumours mimicked malignant mesothelioma. In particular, an awareness that all neoplasms exhibiting squamous differentiation may express cytokeratin 5/6 and thrombomodulin is important to prevent misinterpretation. In this respect, calretinin is regarded as the most specific and sensitive mesothelial marker. Misdiagnosis may have medico–legal implications in asbestos‐related compensation claims.
Microsatellite instability in a pleomorphic rhabdomyosarcoma in a patient with hereditary non‐polyposis colorectal cancer
Authors: Den Bakker M A , Seynaeve C , Kliffen M , Dinjens W N M
Published: December 2004

Aims:  To describe the rare occurrence of a pleomorphic sarcoma with microsatellite instability in a patient with hereditary non‐polyposis colorectal cancer (HNPCC).

Methods and results:  A soft tissue tumour was removed from the upper leg of a patient who had previously been shown to harbour a germ‐line MSH‐2 mutation. The tumour was analysed with immunohistochemistry and molecular methods. The morphology and immunohistochemical findings were in keeping with a pleomorphic rhabdomyosarcoma. Microsatellite instability was documented in the tumour with molecular methods and in addition loss of MSH‐2 expression in the tumour cells was confirmed by immunohistochemistry.

Conclusions:  Although sarcomas do not form part of the HNPCC diagnostic criteria, they may occur in this mismatch repair syndrome and, moreover, may well be caused by the underlying genetic defect.
Synchronous diffuse malignant mesothelioma and carcinomas in asbestos‐exposed individuals
Authors: Attanoos R L , Thomas D H , Gibbs A R
Published: December 2004

Aims:  The development of synchronous diffuse malignant mesothelioma and carcinoma in individuals exposed to asbestos is rare. We report nine cases and discuss the medico–legal implications.

Methods and results:  Five hundred patients seeking compensation for asbestos‐related diffuse malignant mesothelioma were reviewed with access to post‐mortem data. The study group comprised cases in which a second (non‐mesothelial) neoplasm was identified. The study group comprised eight males, one female, mean age 68 years (range 60–75). All individuals gave a history of asbestos exposure. Synchronous malignant mesothelioma with carcinoma was identified in 9/500 (1.8%). Eight malignant mesotheliomas were pleural, one was primary peritoneal in origin. By morphological subtyping there were four epithelioid, three biphasic and two sarcomatoid mesotheliomas. In 6/9 (67%) the second tumour was a primary bronchogenic carcinoma (three adenocarcinomas, two squamous cell carcinomas and one small‐cell carcinoma). In 3/9 (33%) the second tumour was a non‐bronchogenic carcinoma (colonic, pancreatic and breast ductal adenocarcinoma). No other neoplasms were identified in the cohort of malignant mesotheliomas studied. Five persons had pathological evidence of asbestosis (four had bronchogenic carcinomas, one colorectal adenocarcinoma). Two persons with non‐bronchogenic carcinomas had identifiable asbestos bodies but no interstitial fibrosis. In two cases the second neoplasms (primary bronchogenic squamous cell and small‐cell carcinomas) were associated with diffuse interstitial fibrosis but no asbestos bodies were seen on light microscopy. In each case transmission electron microscopic mineral analysis revealed an asbestos fibre burden within the background population range for control subjects and well below that seen in cases of established asbestosis. These cases were considered to represent cryptogenic fibrosing alveolitis in subjects with a history of asbestos exposure.

Conclusions:  Synchronous malignant mesothelioma with carcinomas in asbestos‐exposed workers is rare and identified in 1.8% of 500 malignant mesotheliomas in this series. In most cases the carcinoma represents a primary bronchogenic neoplasm. Primary lung carcinomas are recognized to be asbestos related only when occurring in association with asbestosis. In this series this combination (bronchogenic carcinoma and asbestosis) was seen in four (0.8%) cases. In post‐mortem cases for possible malignant mesothelioma it is important to identify any other neoplasia and determine whether it is related to asbestos. Their presence impact upon anticipated life expectancy and in the presence of malignant mesothelioma will affect the compensation settlement.
Differentiation of ovarian mucinous carcinoma and metastatic colorectal adenocarcinoma by immunostaining with β‐catenin
Authors: Chou Y‐Y , Jeng Y‐M , Kao H‐L , Chen T‐ J , Mao T‐L , Lin M‐C
Published: December 2004

Aims:  To investigate whether localization of β‐catenin is helpful in differentiating primary ovarian mucinous carcinoma and colorectal adenocarcinoma metastatic to the ovary. Extra‐ovarian cancers which metastasize to the ovaries, especially from colorectal adenocarcinoma, frequently mimic primary ovarian carcinomas, particularly endometrioid and mucinous types. Distinguishing primary ovarian carcinoma from metastatic colorectal carcinoma is important for both therapeutic and prognostic reasons. Even after thorough histological examination, metastatic colorectal adenocarcinomas are still often mistaken for primary ovarian adenocarcinomas. Although some tumour makers have been advocated and are helpful in most cases, sometimes the distinction between primary mucinous carcinoma and metastatic colorectal carcinoma remains a problem. Activation of Wnt signalling through mutations of APC or β‐catenin is a key event in the development of colorectal cancer. These mutations lead to nuclear localization of β‐catenin, which can be demonstrated immunohistochemically.

Methods and results:  Formalin‐fixed paraffin‐embedded specimens from 43 primary ovarian mucinous carcinomas and 23 metastatic colorectal adenocarcinomas were included in this study. Sections were immunostained with antibodies to β‐catenin, cytokeratin (CK)7, CK20 and carcinoembryonic antigen (CEA). Nuclear localization of β‐catenin was found in 83% (19/23) of metastatic colorectal cancers and 9% (4/43) of ovarian mucinous carcinomas. Ovarian mucinous carcinomas were usually positive for CK7 (34/43, 79%). For comparison, 40 non‐mucinous carcinomas of the ovary and 42 metastatic adenocarcinomas from other organs were also immunostained with antibodies against β‐catenin. Although nuclear localization of β‐catenin was occasionally seen in non‐mucinous carcinoma of the ovary and metastatic adenocarcinoma from other organs, such tumours were usually distinguishable by their clinicopathological picture and rarely raised diagnostic problems.

Conclusions:  Immunostaining of β‐catenin is a useful marker for differentiating between ovarian mucinous carcinoma and metastatic colorectal adenocarcinoma.
Cystic sclerosing haemangioma of the lung
Authors: Khoury J D , Shephard M N , Moran C A
Published: December 2004

Aims:  To present three cases of sclerosing haemangioma of the lung (SHL) with prominent cystic changes.

Methods and results:  The patients were three women, 27, 35, and 64 years of age. In two cases, the lesion was found on routine chest X‐ray and in both instances the diagnosis of SHL was not entertained in the radiological differential diagnosis. In one case, the finding was discovered on post mortem examination. Grossly, the lesions were well‐circumscribed and cystic. Histologically, the tumours were characterized by a dual population of small and large bland‐appearing neoplastic cells growing in a predominantly cystic pattern. Immunohistochemical staining for epithelial membrane antigen by tumour cells was consistently positive in all three cases. All tumours were negative for keratin, CD34, factor VIII, and S100. The two patients in whom the lesion was identified ante‐mortem are alive and free of disease 4 and 7 years after surgical excision.

Conclusions:  The present cases indicate that sclerosing haemangioma may present as a cystic pulmonary neoplasm; such a presentation should be taken into consideration when assessing cystic pulmonary lesions.
Tumour cell and stromal features in metastatic and non‐metastatic non‐small cell lung carcinomas
Authors: Minamoto H , Antonângelo L , Da Silva A G P , Gallo C P , De Andrade e Silva F B , Fenezelian S , Rodrigues O R , Jatene F , Saldiva P , Capelozzi V L
Published: December 2004

Aims:  Tumour cell behaviour depends on the interactions between nuclear genetic changes in the malignant cells and a stroma favourable for growth, invasion and metastasis. To evaluate such interactions, we studied the relationship between tumour cell and stromal features for proliferative factors, p53, microvessel density and metalloproteinases, controlled for the extent of the primary lesion (T1 to T4), in early (non‐metastatic) and late (metastatic) non‐small cell lung carcinomas (NSCLC).

Methods and results:  Variables were examined for differences and correlations in the frequency of p53, AgNOR, CD34 and MMP‐9 expression in primary lesions and metastases of NSCLC using a general linear model. The patients included 58 males and 22 females (mean age 62 ± 9 years) with 19 T1 (23.8%), 40 T2 (50.0%), 14 T3 (17.5%) and seven T4 (8.8%). In late disease, AgNOR and p53 were statistically related to the extent of the primary lesion, whereas in early disease AgNOR tended to be increased in tumours without metastasis, while p53 expression tended to decrease progressively in tumours with metastasis. Microvessel density in late disease was of no statistical significance, whereas in early disease strong CD34 expression was seen in tumours with metastasis, being at its maximum in T3 primary lesions. The best marker for the extent of the lesion and its progression was MMP‐9, with greater expression by tumours with metastasis than those without.

Conclusions:  Different tumour cell and stromal interactions control metastasis and therefore the biological risk of NSCLC. A panel of molecular markers, such as p53, MMP‐9 and CD34 could help to identify subgroups of patients that could benefit from adjuvant therapy.
Hepatic ‘stem cell’ malignancies in adults: four cases
Authors: Theise N D , Yao J L , Harada K , Hytiroglou P , Portmann B , Thung S N , Tsui W , Ohta H , Nakanuma Y
Published: December 2004

Aims:  Combined hepatocellular/cholangiocarcinomas have been explained by some investigators as bidirectional differentiation of neoplastic progenitor cell populations. The presence of hepatic progenitor cells has now been confirmed in humans, though whether they can give rise to malignant tumours has not been confirmed. We report four cases of small tumours identified in livers with features of chronic hepatitis which may suggest a role for malignant transformation of hepatic stem cells in hepatic malignancies.

Methods:  Tumour samples were studied from four patients by histochemistry and immunohistochemistry.

Results:  Two patients had chronic hepatitis B, one had chronic hepatitis C and chronic alcoholic liver injury, and one had non‐B non‐C chronic hepatitis. Stages of disease ranged from portal fibrosis to cirrhosis. All tumours contained undifferentiated cells with morphological and immunohistochemical features that would be expected of hepatic progenitor cells. These cells merged with both hepatocellular carcinoma and cholangiocarcinoma components as well as with mature appearing hepatocytes within the tumours.

Conclusion:  We suggest that these tumours are of hepatic progenitor cell origin, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells and that such a process may underlie development of some mixed hepatocellular/cholangiocarcinomas and dysplastic nodules.
Phenotypic alteration in malignant transformation of colonic villous tumours: with special reference to a comparison with tubular tumours
Authors: Takata M , Yao T , Nishiyama K‐I , Nawata H , Tsuneyoshi M
Published: December 2004

Aims:  To clarify the cellular differentiation of colorectal villous tumours in malignant transformation, compared with that of tubular tumours (tubular adenoma and adenocarcinoma arising in tubular adenoma).

Methods and results:  Forty‐nine cases of colorectal villous tumours [six cases of low‐grade villous adenoma, 21 of high‐grade villous adenoma (VA), nine of invasive carcinoma in villous adenoma (CIVA), and 13 of pure villous carcinoma (PVC)] and 46 cases of tubular tumours [14 cases of low‐grade and 17 of high‐grade tubular adenoma (TA), and 15 cases of carcinoma in tubular adenoma (CITA)] were selected for this study based on their expression patterns of CD10 (small intestinal brush border), MUC2 (intestinal goblet cell), and HGM (gastric foveolar epithelium). HGM was more frequently expressed in the adenomatous components of villous tumours (63%) than in those of tubular tumours (14%) (P < 0.05). CD10 expression of high‐grade TAs (47%) and carcinomas arising in TA (60%) was significantly higher than that of villous tumours (0%) (P < 0.05).

Conclusions:  There were significant differences in the phenotypic expression of adenoma and adenocarcinoma between villous and tubular tumours, respectively. Villous tumours have a pathway of malignant transformation different from that of tubular tumours. Because of biological differences, colorectal villous tumours should be distinguished from tubular neoplasia. The analysis of the phenotype of colorectal neoplasms is useful for the evaluation of tumour progression.
Altered expression of DNA double‐strand break detection and repair proteins in breast carcinomas
Authors: Angèle S , Treilleux I , Brémond A , Tanière P , Hall J
Published: December 2004

Aims:  To determine whether the expression of DNA damage detection and repair proteins is frequently altered in breast carcinomas.

Methods and results:  The expression profiles of five such proteins: ATM, p53, NBS1, MRE11 and Rad50 were analysed in 99 in‐situ and invasive ductal breast carcinomas of different grades using an immunohistochemical approach, and compared with those seen in eight independent non‐cancer (normal) breast samples and in the surrounding normal tissues of the breast carcinomas examined. ATM protein expression was reduced in 75% of the tumours compared with the levels found in normal tissues. Fewer tumours had reduced protein levels of the members of the MRE11, NBS1 and Rad50 (MNR) complex (31%, 46% and 28%, respectively) with p53 being over‐expressed in 30%. In the majority of tumours (92%) we observed a good correlation between the expression of the three proteins of the MNR complex with low NBS1, MRE11 or Rad50 expression rarely found alone, suggesting that this event occurs subsequently to the deregulation in expression of other DNA repair proteins.

Conclusion:  The pattern of protein changes observed supports our hypothesis that alterations in DNA double‐strand break repair capacity are involved in mammary carcinogenesis.
Refining the diagnosis of hydatidiform mole: image ploidy analysis and p57KIP2 immunohistochemistry
Authors: Crisp H , Burton J L , Stewart R , Wells M
Published: December 2004

Aim:  To determine whether image analysis of ploidy status and immunohistochemical analysis of p57KIP2 (a paternally imprinted, maternally expressed gene) can be used to refine the diagnosis of molar pregnancy.

Methods and results:  The original histological diagnosis in 40 randomly selected cases of hydatidiform mole was reviewed and confirmed in 38 cases (22 complete moles, 16 partial moles). These cases were anonymized and submitted for further analysis. Tissue from each case was submitted for flow cytometric assessment of DNA ploidy using a FACSort flow cytometer and for automated image cytometric assessment using a novel digital imaging system. Tissue sections from each case were immunostained with a monoclonal mouse antibody to p57KIP2. Correlations between the histopathological diagnosis, image cytometry, flow cytometry and p57KIP2 immunohistochemistry were determined using κ statistics. The concordance between histological diagnosis and p57KIP2 was very good (κ = 0.89). Twenty of the 22 (90.9%) complete moles showed no immunoreactivity for p57KIP2. The remaining two cases showed nuclear immunoreactivity in villous cytotrophoblast. In one of these, the pattern of staining resembled that of a partial mole. In the other, the staining pattern supported the diagnosis of a twin molar/non‐molar pregnancy. All 16 partial moles were p57KIP2 immunoreactive. On flow cytometry, all 22 complete moles were diploid and 12/16 partial moles were triploid (the remaining four cases originally diagnosed as partial moles were found to be diploid). On image cytometry, one case originally diagnosed as complete mole was found to contain a triploid population. Thus, by using a combination of image cytometry and p57KIP2 status we were able to refine the diagnosis of molar pregnancy in five (13%) of the cases studied.

Conclusions:  Automated image cytometry is a readily performed investigation which is comparable to, but more sensitive than, flow cytometry. Complementary use of ploidy analysis and p57KIP2 status can now help to distinguish a diploid hydropic miscarriage (p57KIP2‐positive), diploid complete mole (p57KIP2‐negative) and triploid partial mole (p57KIP2‐positive).
Decrease of Deleted in Malignant Brain Tumour‐1 (DMBT‐1) expression is a crucial late event in intrahepatic cholangiocarcinoma
Authors: Sasaki M , Huang S‐F , Chen M‐F , Jan Y‐Y , Yeh T‐S , Ishikawa A , Mollenhauer J , Poustka A , Tsuneyama K , Nimura Y , Oda K , Nakanuma Y
Published: December 2004

Aims:  To investigate the participation of DMBT‐1, a candidate tumour suppressor gene, in the development of intrahepatic cholangiocarcinoma via intraductal papillary neoplasm of the liver (IPN‐L) arising in hepatolithiasis. DMBT‐1 plays a role in mucosal immune defence.

Methods and results:  The expression of DMBT‐1 was examined immunohistochemically in biliary epithelial cells in hepatolithiasis (n = 25), invasive and non‐invasive cholangiocarcinoma associated with hepatolithiasis (n = 52), IPN‐L with hepatolithiasis (n = 49), cholangiocarcinoma without hepatolithiasis (n = 32), and 10 normal control livers. DMBT‐1 was expressed more frequently in the biliary epithelia of hepatolithiasis when compared with normal livers (P < 0.05). DMBT‐1 expression was also frequent in IPN‐L (57%) and non‐invasive cholangiocarcinoma (79%). By contrast, DMBT‐1 was decreased in invasive cholangiocarcinoma with and without hepatolithiasis (50% and 30%, respectively) (P < 0.05). The homozygous deletion of the DMBT‐1 gene was recognized in four (20%) of 20 cholangiocarcinoma tissues and two (50%) of four cholangiocarcinoma cell lines, corresponding to the reduction of DMBT‐1 expression. No deletion was detected in hepatolithiasis tissues.

Conclusion:  DMBT‐1 expression is increased in IPN‐L and non‐invasive cholangiocarcinoma as well as in biliary epithelia in hepatolithiasis. Decreased expression of DMBT‐1 and homozygous deletion of the DMBT‐1 gene in invasive cholangiocarcinoma suggest that they occur in the late stage of cholangiocarcinogenesis.
Analysis of the prognostic implications of different tumour margin types in renal cell carcinoma
Authors: Thomas D H , Verghese A , Kynaston H G , Griffiths D F R
Published: December 2004

Aims: Invasion of perinephric tissues is part of the Union Internationale Contre le Cancer (UICC) (1997) T staging criteria for renal cell carcinoma (RCC) and appears to confer a worse prognosis. However, there are no established histological criteria to determine if this has occurred and histopathologists differ in their interpretation of the tumour margin. The purpose of this study was to determine histological criteria for invasion of perinephric tissues that may be used in staging.

Methods and results: We assessed the prognostic implications of different margin types in 176 cases of RCC with good follow‐up data. The tumour margin type in each cases was classified as follows: fibrous tumour capsule; rim of kidney; fibrous capsule with ‘collar stud’ invasion; pushing margin, no capsule; and tumour cell invasion of fat. The margin types were used in univariate and multivariate survival analysis to determine which had most impact on disease‐free survival. In Cox regression analysis with all other influential covariates cellular invasion of fat was the only margin type that had any prognostic impact, conferring a 2.9 relative hazard compared with tumours with a fibrous capsule (P = 0.007).

Conclusions: For staging purposes the designation of a tumour as invading perinephric tissues should be limited to those cases that have tumour cells invading the perinephric fat.
ALK‐negative anaplastic large‐cell lymphoma demonstrates similar poor prognosis to peripheral T‐cell lymphoma, unspecified
Authors: Ten Berge R L , De Bruin P C , Oudejans J J , Ossenkoppele G J , Van Der Valk P , Meijer C J L M
Published: December 2004

Aims:  Anaplastic large cell lymphoma (ALCL) is classically considered a clinicopathological entity separate from other nodal mature T‐cell lymphomas (TCL). Recently, the anaplastic lymphoma kinase (ALK) protein was shown to identify a subgroup of nodal ALCL with an excellent prognosis, whereas ALK‐negative ALCLs are more heterogeneous. The aim of this study was to investigate the clinicopathological parameters in relation to clinical behaviour of ALK‐negative ALCL compared with other nodal mature TCL, i.e. peripheral TCL, unspecified (PTCL‐NOS) and angioimmunoblastic lymphoma (AILT).

Methods and results:  Clinicopathological data of ALK‐positive (n = 28) and ALK‐negative (n = 46) ALCL; PTCL‐NOS (n = 47); and AILT (n = 12) were analysed for their prognostic significance. While ALK‐positive ALCL shows favourable clinical features and a good prognosis, ALK‐negative ALCL, PTCL‐NOS and AILT are all associated with high age groups, advanced disease stage, and poor prognosis (<45% 5‐year survival). In multivariate analysis of overall survival time, performed in the combined group of ALK‐negative nodal mature T‐cell lymphomas, only age and the International Prognostic Index (IPI) remained independent prognostic parameters, while lymphoma subtype (ALCL versus PTCL‐NOS versus AILT) gave no additional information.

Conclusions:  The distinction between ALK‐negative ALCL and PTCL‐NOS or AILT is of limited clinical relevance as they show comparable poor prognosis. In these lymphoma subtypes, only age and the IPI are of significant prognostic value.
MOC‐31/Ep‐CAM immunoreactivity in Merkel cells and Merkel cell carcinomas
Authors: García‐Caballero T , Pintos E , Gallego R , Parrado C , Blanco M , Bjornhagen V , Forteza J , Beiras A
Published: December 2004

Aims:  To evaluate the monoclonal antibody MOC‐31 in Merkel cell carcinomas and normal Merkel cells. Merkel cell carcinoma is a rare and aggressive tumour that occurs mainly in elderly individuals. The histological diagnosis of Merkel cell carcinoma can be difficult because it looks similar to other small blue cell tumours, particularly skin metastases of small‐cell lung carcinomas. This antibody recognizes the epithelial cell adhesion molecule (Ep‐CAM), that has been assigned to the small cell lung cancer cluster 2 of antibodies. To the best of our knowledge, immunostaining for MOC‐31/Ep‐CAM has not been previously described in Merkel cells or Merkel cell carcinomas.

Methods and results:  Thirty‐one cases of Merkel cell carcinoma and three samples of normal human fingertip were selected to analyse the expression of MOC‐31/Ep‐CAM by immunohistochemistry. A high number of Merkel cell carcinomas (21/31, 67.7%) showed intense and readily interpretable positivity. Immunostaining was diffuse or focal and always localized to the plasma membrane. Normal Merkel cells of human fingertip also showed plasma membrane immunoreactivity for MOC‐31/Ep‐CAM.

Conclusion:  The demonstration of positivity for MOC‐31/Ep‐CAM in Merkel cell carcinomas precludes the use of this immunohistochemical marker to distinguish between tumours and skin metastases of small‐cell lung carcinoma.
The role of flat and depressed colorectal lesions in colorectal carcinogenesis: new insights from clinicopathological findings in high‐magnification chromoscopic colonoscopy
Authors: Hurlstone D P , Brown S , Cross S S
Published: December 2004

High‐magnification chromoscopic endoscopy is a new technique which has been recently introduced to the UK. This technology, initially pioneered by the Japanese in the 1980s, has changed our understanding of the pathogenesis of colorectal cancer and our subsequent therapeutic strategies aimed at the secondary prevention of cancer. Magnification colonoscopic techniques when combined with colonic chromoscopy (dye spraying of the colon) permit in vivo assessments of lesions at a magnification and resolution similar to a stereomicroscope. Furthermore, flat/depressed adenomas and cancers can be diagnosed with increasing frequency and new resection practices performed. This technique is known as endoscopic mucosal resection. As gastrointestinal endoscopists adopt these new techniques, close liaison with histopathologists is essential to provide the highest standards of diagnostic accuracy. The histopathologist also needs to be aware of the endoscopic findings when interpreting specimens and hence must understand new endoscopic terminologies and classification systems that accompany the introduction of new technologies and therapeutic techniques. This article describes the controversies relating to the flat and depressed colorectal lesion, where these new endoscopic technologies are ideally suited. It then provides a working description of high‐magnification chromoscopic colonoscopy including the Japanese ‘pit pattern’ and morphological classification system—information which will be provided to histopathologists with specimens obtained by these new techniques. Finally, we describe the procedure of endoscopic mucosal resection, as the type and quality of specimens received for histopathological analysis will be highly influenced by these techniques.
BRITISH DIVISION OF THE INTERNATIONAL ACADEMY OF PATHOLOGY
Authors: Van Den Tweel J , Howat A J , Shepherd N A , Francis N , Harris C
Published: December 2004

10‐‐15 October 2004 XXVth International Congress. Brisbane, Australia

26‐‐27 November 2004 Symposium on Pulmonary Pathology.London, UK
A preliminary in vitro study of the incidence and position of the root canal isthmus in maxillary and mandibular first molars
Authors: Teixeira F. B. , Sano C. L. , Gomes B. P. F. A. , Zaia A. A. , Ferraz C. C. R. , Souza‐Filho F. J.
Published: December 2004

Aim  To investigate in vitro the incidence and position of the root canal isthmus in extracted mesiobuccal roots of maxillary and mesial roots of mandibular first molars.

Methodology  Fifty maxillary and 50 mandibular molars were included in the study. The mesiobuccal roots of maxillary molars and the mesial roots of mandibular molars were sectioned from their crowns in the furcation region and embedded in clear resin. Transverse serial 1‐mm‐thick sections from the apical 6 mm were prepared. The apical side of each section was stained with India ink and observed through a light microscope. The sample images were saved to disk using a digital camera and the root canals in terms of the number present and the incidence and classification of isthmuses.

Results  In the mesiobuccal root of the maxillary first molars, 70% had one canal, whereas 29.5% had two canals. In the mesial root of mandibular molars, 41% had one canal, whereas 59% had two canals. In some sections, more than two canals were found close to the apical foramen. The isthmus incidence was greatest 3–5 mm from the apex. In teeth having two canals, a complete or partial isthmus was frequently observed in the sections between 3 and 4 mm from the apex. Of the isthmuses present, 22% were complete and 37% partial in mandibular molars and 17.3% were complete and 11.7% partial in maxillary molars.

Conclusions  The incidence of isthmus in the mesiobuccal root of the maxillary first molars and in the mesial root of the mandibular first molars was high, particularly in sections 3–5 mm from the apex. Cleaning the isthmus is a major challenge during root canal treatment.
Evaluation of damage to the testicular cells of golden hamsters caused by experimental cryptorchidism using flow cytometry and confocal microscopy
Authors: Vigodner M. , Lewin L. M. , Shochat L. , Oschry I. , Lotan G. , Kleen B. , Golan R.
Published: December 2004

Artificial unilateral cryptorchidism was performed in golden hamsters which were then held for different periods of time. The non‐operated side was used as a control. At various times from 4 to 15 days, hamsters were killed, testes were removed and weighed, single cell suspensions were prepared for flow cytometry analysis and seminiferous tubules were fixed for confocal microscopy. Using DNA staining by propidium iodide or acridine orange followed by flow cytometry analysis, a marked decrease in the haploid condensed cell fraction was detected at the beginning stages of experimental cryptorchidism. In correlation with flow cytometry results, spermiogenic arrest at stages IX and X of seminiferous epithelium was detected in these animals by confocal microscopy and there were no mature forms of haploid cells in the cryptorchid testis. In the testis with more severe damage, there were almost no haploid cells in the seminiferous tubules of cryptorchid animals. In addition, a significant decrease in tetraploid cell fraction and an increase in S‐phase fraction was obtained in severe cases. This may be explained by cell arrest before entrance into meiosis. Destruction of tubule structure and cell arrangement were also observed by confocal microscopy in such cases.

In conclusion, flow cytometry, combined with confocal analysis, added useful information about spermatogenesis disturbances in cryptorchid testis and it may be used as diagnostic tools in other cases of spermatogenic disorders.
The Y chromosome and male fertility and infertility1
Authors: Krausz Csilla , Forti G. , McElreavey Ken
Published: December 2004

Since 1995, thanks to a large number of studies, Y chromosome microdeletion screening has become part of the routine diagnostic work‐up of severe male factor infertility. Many initial contradictory issues such as variability in deletion frequency, markers to be tested, presence of deletions in ‘fertile’ men, and genotype–phenotype correlation has been resolved. Past and present unresolved issues are discussed in this review.
Participation of superoxide anion in the capacitation of cryopreserved bovine sperm
Authors: O'Flaherty C. , Beorlegui N. , Beconi M. T.
Published: December 2004

Mammalian spermatozoa must undergo a preparation period known as capacitation to become capable of fertilizing oocytes. Controlled amounts of reactive oxygen species (ROS), such as superoxide anion (O2·–) and hydrogen peroxide (H2O2) have been shown essential for capacitation and acrosome reaction. The presence of an oxidase in the sperm plasma membrane has been suggested. The objective of the present study was to provide evidence for the production of O2·–by capacitating cryopreserved bovine spermatozoa. Percentages of capacitation and acrosome reaction were determined by the chlortetracycline assay. The effect of several nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors on capacitation was also studied. H2O2production was determined by the fluorometric assay using thep‐hydroxyphenylacetic acid‐horseradish peroxidase system. Superoxide dismutase (SOD) activity was determined spectrophotometrically at 480 nm. Heparin‐dependent capacitation was inhibited by all NADPH oxidase inhibitors tested (p < 0.05). Significant levels of H2O2were produced during capacitation with heparin; such production was inhibited by diphenyleneiodonium, one of the NADPH oxidase inhibitors. The addition of catalase to the incubation medium failed to modify the capacitation rate; inhibition was only observed when SOD was present (p < 0.05). Endogenous SOD activity was diminished during heparin‐dependent capacitation (p < 0.05). Similar levels of acrosome reaction induced by lysophosphatidylcholine were obtained in both heparin and O2·–‐dependent capacitation. Overall results suggest the participation of a sperm oxidase in bovine sperm capacitation. H2O2, generated by O2·–dismutation, failed to participate in capacitation, although this ROS may have been able to decrease endogenous SOD activity. Exogenous O2·–promotes physiological capacitation in cryopreserved bovine sperm, thus allowing the acquisition of fertilizing capacity.
The role of the c‐kit receptor in the regenerative differentiation of rat Leydig cells
Authors: Tsuchida Junji , Dohmae Kayoko , Kitamura Yukihiko , Nishimune Yoshitake
Published: December 2004

To determine the physiological role of the c‐kit receptor, which is highly expressed in Leydig cells, the regenerative differentiation of Leydig cells was studied following transient degeneration induced by ethane dimethyl sulphonate (EDS) in c‐kit‐deficient mutant rats (Ws/Ws). EDS caused the destruction of Leydig cells; their functional recovery was evaluated by the weight change of the target organs of androgens, which occurred at the same rate in Ws/Ws and wild‐type rats. These results indicate that the tyrosine kinase activity of the c‐kit receptor does not play an essential role in the regenerative differentiation of Leydig cells.
Changes in retinoblastoma gene expression during cervical cancer progression
Authors: Salcedo Mauricio , Taja Lucía , Utrera Dolores , Chávez Pedro , Hidalgo Alfredo , Pérez Carlos , Benítez Luis , Castañeda Cristina , Delgado Ricardo , Gariglio Patricio
Published: December 2004

Summary. The role of tumour suppressor genes in the development of human cancers has been studied extensively. In viral carcinogenesis, the inactivation of suppressor proteins such as retinoblastoma (pRb) and p53, and cellular oncogenes overexpression, such as c‐myc, has been the subject of a number of investigations. In uterine‐cervix carcinomas, where high‐risk human papillomavirus (HPV) plays an important role, pRb and p53 are inactivated by E7 and E6 viral oncoproteins, respectively. However, little is known about the in situ expression of some of these proteins in pre‐malignant and malignant cervical tissues. On the other hand, it has also been demonstrated that c‐myc is involved in cervical carcinogenesis, and that pRb participates in the control of c‐myc gene expression. By using immunostaining techniques, we investigated pRb immunodetection pattern in normal tissues, squamous intraepithelial lesions (SILs) and invasive carcinomas from the uterine cervix. Our data show low pRb detection in both normal cervical tissue and invasive lesions, but a higher expression in SILs. C‐Myc protein was observed in most of the cellular nuclei of the invasive lesions, while in SILs was low. These findings indicate a heterogeneous pRb immunostaining during the different stages of cervical carcinogenesis, and suggest that this staining pattern could be a common feature implicated in the pathogenesis of uterine‐cervix carcinoma.