bluuebunny/crossref_metadata_2025_split huggingface dataset:
Over‐expression of tenascin‐C in malignant pleural mesothelioma
Authors: Kaarteenaho‐Wiik R , Soini Y , Pöllänen R , Pääkkö P , Kinnula V L 
Published: December 2004

Aims:  Tenascin‐C is an extracellular matrix glycoprotein known to have anti‐adhesive characteristics and to be expressed in various human malignant neoplasms. We hypothesized that the expression of tenascin‐C would be increased in human malignant pleural mesothelioma, and its accumulation associated with the prognosis of the patients with this disease.Methods and results:  Thirty‐seven cases of mesothelioma were studied by immunohistochemically using a monoclonal antibody against tenascin‐C, and with a semiquantitative scoring system for tenascin‐C in different areas of the tumours. In 10 selected cases tenascin‐C mRNA in‐situ hybridization was also analysed. Since transforming growth factor‐beta (TGF‐β) is known to induce both the synthesis of tenascin‐C and the growth of mesotheliomas, an immunohistochemical analysis of TGF‐β1, ‐β2 and ‐β3 was also performed. Normal pleura (n = 7) and metastatic pleural adenocarcinomas (n = 7) were used as controls. Tenascin‐C protein was expressed in every histological subtype of malignant mesothelioma, being most prominent in the fibrotic stroma of a tumour, around tumour cells and at the invasive border, whereas tenascin‐C mRNA was scarce in tumour cells. The patients with less immunohistochemical expression for tenascin‐C tended to live longer (P = 0.028 by Fishers' exact probability test). All mesotheliomas showed positivity for at least one isoform of TGF‐β.Conclusions:  In conclusion, high expression of tenascin‐C protein in malignant pleural mesotheliomas may play a role in its invasive growth, and might serve as a prognostic marker of the disease.
The pathology of acute hepatic disintegration in hereditary haemorrhagic telangiectasia
Authors: Blewitt R W , Brown C M , Wyatt J I 
Published: December 2004

Aims:  Hereditary haemorrhagic telangiectasia is a rare inherited disease in which telangiectases affect skin, mucous membranes and the gastrointestinal tract. Hepatic involvement is common but usually asymptomatic. We report a case of acute hepatic disintegration in hereditary haemorrhagic telangiectasia, document the histopathological findings and present a hypothesis to explain them.Methods and results:  The patient presented at the age of 34 years with abdominal pain, leading to the surgical removal of a severely inflamed gallbladder. Signs of liver damage became increasingly apparent over the next few weeks, with disruption of the intrahepatic biliary tree and marked vascular shunting, necessitating liver transplantation. Six months after the transplant a diagnosis of hepatic hereditary haemorrhagic telangiectasia was made. The principal features of hepatic hereditary haemorrhagic telangiectasia are periportal telangiectases and sinusoidal congestion and dilatation. Acute hepatic disintegration is characterized by disruption of liver structure, hepatocyte necrosis, haemorrhage and extravasation of bile.Conclusions:  Periportal telangiectases in a liver biopsy are highly suggestive of hereditary haemorrhagic telangiectasia. Acute hepatic disintegration is likely to be a consequence of rupture of telangiectases and ischaemic necrosis of intrahepatic bile ducts. Patients with hereditary haemorrhagic telangiectasia are at risk of acute hepatic disintegration following intra‐abdominal sepsis.
Erythropoietin as an angiogenic factor in gastric carcinoma
Authors: Ribatti D , Marzullo A , Nico B , Crivellato E , Ria R , Vacca A 
Published: December 2004

Aims:  Previous studies have shown that increased vascularity is associated with haematogenous metastasis and poor prognosis in gastric cancer. The role of erythropoietin (Epo) in angiogenesis has not been completely clarified, although its involvement has been reported. In this study we correlated microvascular density and Epo receptor (Epo‐R) expression in endothelial and tumour cells with histopathological type in gastric cancer.Methods and results:  Specimens of primary gastric adenocarcinomas obtained from 40 patients who had undergone curative gastrectomy were investigated immunohistochemically by using anti‐CD31 and anti‐Epo‐R antibodies. Stage IV gastric carcinoma had a higher degree of vascularization than other stages, and Epo‐R expression in both endothelial and tumour cells increased in parallel with malignancy grade and was highly correlated with the extent of angiogenesis.Conclusions:  Epo‐R level correlates with angiogenesis and progression of patients with gastric carcinoma and we suggest that Epo might have a trophic effect on the vasculature of the gastrointestinal tract. Understanding mechanisms of gastric cancer angiogenesis provides a basis for a rational approach to the development of an anti‐angiogenic therapy in patients with gastric cancer.
Expression of HER‐2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in‐situ hybridization and immunohistochemistry
Authors: Skálová A , Stárek I , Vanecek T , Kucerová V , Plank L , Szépe P , Di Palma S , Leivo I 
Published: December 2004

Aims:  Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER‐2/neu oncogene and over‐expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER‐2/neu using immunohistochemistry (IHC) has shown over‐expression in most cases. However, correlation between IHC and molecular genetic analysis of HER‐2/neu in salivary duct carcinoma has not yet been performed.Methods and results:  We have now evaluated 11 cases of salivary duct carcinomas for HER‐2/neu status using IHC and fluorescent in‐situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER‐2/neu in salivary duct carcinoma.Conclusions:  In immunohistochemistry, over‐expression of HER‐2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER‐2/neu gene by means of FISH analysis. Both amplified and non‐amplified salivary duct carcinomas with strong immunohistochemical staining for HER‐2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER‐2/neu protein over‐expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over‐expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over‐expression of HER‐2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.
Smooth muscle cell differentiation in mammary stromo‐epithelial lesions with evidence of a dual origin: stromal myofibroblasts and myoepithelial cells
Authors: Di Tommaso L , Pasquinelli G , Damiani S 
Published: December 2004

Aims:  We investigated the origin of myoid cells in benign stromo‐epithelial lesions of the breast in order to ascertain their myoepithelial or myofibroblastic origin.Methods and results:  We selected 22 stromo‐epithelial lesions of the breast and reviewed their morphological features at haematoxylin–eosin (H&E) level. The lesions were classified as fibrous stromo‐epithelial lesions (without evidence of myoid differentiation at H&E level) (13 cases), type 1 myoid stromo‐epithelial lesions (myoid cells directly merging with the myoepithelial layer) (three cases), type 2 myoid stromo‐epithelial lesions (bundles of myoid cells unrelated to the glands) (six cases). All cases were studied immunohistochemically and myoid stromo‐epithelial lesions were also studied with electron microscopy. The myoid component in two out of three cases of type 1 myoid lesions showed immunohistochemically co‐expression of smooth muscle and myoepithelial markers. In contrast, the remainder showed immunohistochemical results identical to those found in type 2 myoid lesions (positivity with SMA, desmin, calponin, CD34 and bcl2 and negativity with cytokeratin 14 and p63). Ultrastructural study confirmed the presence of cells with myoepithelial features in type 1 myoid lesions and of cells with myofibroblastic features in type 2 myoid lesions.Conclusions:  Myoid cell differentiation is common in stromo‐epithelial lesions of the breast, and is evident in H&E sections in up to 40% of cases. In addition, the origin of myoid cells is myofibroblastic in most cases, but in some cases, cells present immunohistochemical and ultrastructural evidence of myoepithelial origin.
Microvessel densities and microvascular architecture in colorectal carcinomas and their liver metastases: significant correlation of high microvessel densities with better survival
Authors: Prall F , Gringmuth U , Nizze H , Barten M 
Published: December 2004

Aims:  Microvessel densities in cancers have been shown to be a prognostic factor for some types of cancer. For colorectal cancer, however, the situation is far from clear.Methods:  A consecutive series of 173 colorectal carcinomas was investigated, and to these were added 55 liver metastases originating from colorectal cancer. Microvessels were counted in hotspots (factor VIII immunostaining, 0.74 mm2). The capillary architecture was scored according to the degree of order and envelopment of the neoplastic glands. Endothelial proliferation was determined by factor VIII/Ki67 double labelling.Results:  Mean microvessel densities were 51.8 for colorectal carcinomas (range 8–140) and 31.9 for liver metastases (range 3–101). Stratification according to stage, depth of infiltration and nodal involvement showed a significant inverse relation with increase. Mean microvessel densities in primaries were significantly higher than in metastases. Kaplan–Meier analysis showed a significantly higher cancer‐specific survival for high microvessel densities (median as cut‐off) and for a more ordered microvascular architecture. Endothelial proliferation in carcinomas was significantly higher than in normal mucosa.Conclusions:  Contrary to other types of cancer, for colorectal cancer high microvessel densities confer good rather than poor prognosis. We hypothesize that neoangiogenesis, though extant in colorectal cancer, is not rate‐limiting in the metastatic cascade.
Colorectal carcinomas with high MIB‐1 labelling indices but low pKi67 mRNA levels correlate with better prognostic outcome
Authors: Duchrow M , Ziemann T , Windhövel U , Bruch H‐P , Broll R 
Published: December 2004

Aims:  Antibodies specific to the proliferation‐associated protein pKi67 (e.g. Ki67, MIB‐1) are routinely used in oncology to assess the proliferation index of tumour cells. In untransformed cells the amount of pKi67 present at any time of the cell cycle is strictly regulated. To achieve a better understanding of expression and regulation of this protein in tumour cells, we investigated both pKi67 mRNA and protein expression in routinely fixed and embedded tissue of colorectal carcinoma.Methods and results:  We determined a median pKi67 specific in‐situ hybridization labelling index of 42% (9–79%) and a median Ki67 index (MIB‐1 labelling index) of 59% (26–94%) in 47 resected colorectal adenocarcinomas of different stages and grades. In 32 cases expression of pKi67 mRNA and protein correlated well but we observed a significant difference between both values in 15 tumours. In these cases more than 30% of the cells expressed the protein but not the mRNA of pKi67, possibly due to cell cycle arrest. Patients belonging to this group had a significantly (P < 0.012) better prognosis.Conclusions:  Tumours with a high pKi67 protein level but low mRNA expression are likely to proliferate more slowly than calculated on the basis of their Ki67 staining index, which possibly explains the patients' improved outcome.
Expression of HMGI(Y) associated with malignant phenotype of human gastric tissue
Authors: Nam E S , Kim D H , Cho S J , Chae S W , Kim H Y , Kim S M , Han J J , Shin H S , Park Y E 
Published: December 2004

Aims:  We evaluated the association between HMGI(Y) expression and the detection of malignant cells by simple reverse transcriptase‐polymerase chain reaction (RT‐PCR) and correlated the level of HMGI(Y) expression and the clinicopathological data in gastric cancer.Methods and results:  We analysed HMGI(Y) expression in 62 gastric cancer tissues and 28 normal gastric tissues by RT‐PCR and immunohistochemical study. HMGI(Y) expression evidenced by RT‐PCR was observed in 42 (67.7%) of 62 gastric cancer samples, whereas eight (28.6%) of 28 normal gastric tissues were positive (P = 0.001). In immunohistochemical staining for HMGI(Y), 48 (77.4%) of 62 gastric cancers were positive for HMGI(Y), whereas four (6.5%) of 62 normal gastric mucosae around the tumour were weakly positive, particularly in cells of some hyperplastic glands (P < 0.001). There was no significant correlation between the levels of HMGI(Y) expression and stage, tumour size, histological grade, invasion depth, or lymph node metastasis.Conclusions:  Our results suggest that HMGI(Y) expression could be associated with malignant phenotype in human gastric tissue, and that HMGI(Y) may contribute to gastric tumorigenesis.
Ossifying fibromyxoid tumour of soft parts, with focus on unusual clinicopathological features
Authors: Holck S , Pedersen J G , Ackermann T , Daugaard S 
Published: December 2004

Aims:  Ossifying fibromyxoid tumour is a rare lesion that generally occurs in the soft tissues of proximal limbs/girdle, or head and neck. Histologically, it usually consists of bland, mitotically inactive, S100+ cells in a fibromyxoid matrix with a characteristic peripheral ossification. However, we present two cases that deviated from this pattern.Material and methods:  One tumour, which was removed from the axilla of a 55‐year‐old female, was unusual in its large size (120 mm in diameter) and in its restriction of bone formation to its central zones. The other tumour, which occurred in a 62‐year‐old female, was remarkable in its acral location on the hand and high mitotic activity (four mitoses per high‐power field). These features caused concern and follow‐up of the patients was recommended. So far there have been no recurrences (25 and 18 months after surgery, respectively). An additional previously undescribed feature was the presence of fibronexus‐like structures by electron microscopy in the second case. However, a myofibroblastic phenotype was not supported by the immunohistochemical findings.Conclusion:  Though a distinct entity, ossifying fibromyxoid tumour may exhibit a wider clinicopathological spectrum than generally recognized.
Haemorrhagic dermatomyofibroma (plaque‐like dermal fibromatosis): clinicopathological and immunohistochemical analysis of three cases resembling plaque‐stage Kaposi's sarcoma
Authors: Mentzel T , Kutzner H 
Published: December 2004

Aims:  Dermatomyofibroma (plaque‐like dermal fibromatosis) represents a distinct clinicopathological entity in the spectrum of cutaneous mesenchymal neoplasms showing a myofibroblastic line of differentiation. These benign neoplasms occur frequently, but not exclusively, in young women, and the shoulder girdle as well as the upper trunk are common locations. Histologically, dermatomyofibroma is characterized by a plaque‐like proliferation of cytologically bland spindle‐shaped tumour cells containing an ill‐defined, pale eosinophilic cytoplasm and elongated, neuroid nuclei. Neoplastic cells are arranged in bundles and fascicles orientated parallel to the skin surface, adnexal structures are spared and elastic fibres are increased and fragmented. Immunohistochemically, tumour cells express vimentin and variably muscle actin and α‐smooth muscle actin, but are negative for desmin, CD34, S100, and epithelial markers. The main differential diagnosis includes hypertrophic scar, dermatofibroma (fibrous histiocytoma), pilar leiomyoma, neurofibroma, adult myofibromatosis, extra‐abdominal fibromatosis and plaque‐stage dermatofibrosarcoma protuberans.Methods and results:  We report three cases of dermatofibroma arising in male patients aged 31, 36, and 47 years on the thigh, chest wall and back, respectively. All lesions were completely excised and no local recurrence has been reported. Histologically, the neoplasms showed classical features of dermatomyofibroma; however, in addition abundant extravasated erythrocytes, scattered inflammatory cells, numerous capillaries, and sieve‐ and slit‐like spaces, features resembling plaque‐stage Kaposi's sarcoma, were noted. In none of the cases did spindled tumour cells stain positively for CD34, and HHV8 was not detected by polymerase chain reaction.Conclusions:  The reported cases widen the clinicopathological spectrum of dermatomyofibroma and emphasize plaque‐stage Kaposi's sarcoma as an additional differential diagnosis.
E‐cadherin loss rather than β‐catenin alterations is a common feature of poorly differentiated thyroid carcinomas
Authors: Rocha A S , Soares P , Fonseca E , Cameselle‐Teijeiro J , Oliveira M C , Sobrinho‐Simões M 
Published: December 2004

Aims: To investigate the immunohistochemical and molecular genetic features of the cadherins/catenins complex in thyroid carcinoma based on the hypothesis that poorly differentiated carcinoma of the thyroid represents an intermediate step between well‐differentiated and undifferentiated carcinomas.Methods and results: Immunohistochemistry for E‐, P‐ and N‐cadherins and α‐, β‐ and γ‐catenins was performed in a series of 17 cases of poorly differentiated carcinoma of the thyroid. All cases showed absence of membranous expression of E‐cadherin with no aberrant expression of P‐ or N‐cadherins; regarding catenins there was heterogeneous loss of expression with membranous immunolocalization of the three catenins in most cases. Molecular analysis of the E‐cadherin gene and exon 3 of the β‐catenin gene was also performed by polymerase chain reaction/single‐strand conformation polymorphism and sequencing. No mutations in either gene were detected in any case.Conclusions:  In contrast to previous reports, our results suggest that loss of E‐cadherin rather than β‐catenin mutation is the crucial event in determining the differentiation ‘level’ of thyroid carcinomas.
Lack of histologically suspicious features, proliferative activity, and p53 expression suggests benign diagnosis in phaeochromocytomas
Authors: Salmenkivi K , Heikkilä P , Haglund C , Louhimo J , Arola J 
Published: December 2004

Aims:  The malignancy of phaeochromocytomas is difficult to predict. Traditionally, only a metastasized tumour is considered malignant. The aim of this study was to assess the histopathological and clinical features, as well as the proliferative activity, and to analyse p53 and p21 expression in 105 phaeochromocytomas.Methods and results:  All malignant phaeochromocytomas (n = 8) showed at least one of the histologically suspicious features, i.e. over five mitoses/10 high‐power fields, necrosis, capsular or vascular invasion. Malignant tumours were larger, but the age and gender of the patients were not significantly different. All benign (n = 33) and most of the borderline (18/21) adrenal phaeochromocytomas had less than 6% Ki67+ tumour cells, while most malignant tumours (6/7) expressed Ki67 in >6% of the cells. p53+ immunohistochemistry was found in two malignant tumours, while p21 expression did not correlate with malignancy.Conclusions:  These data suggest that the lack of histologically suspicious features, low proliferative activity, smaller size, and negative p53 immunostaining point to a benign diagnosis in phaeochromocytomas.
HER2 oncogene amplification in extramammary Paget's disease
Authors: Tanskanen M , Jahkola T , Asko‐Seljavaara S , Jalkanen J , Isola J 
Published: December 2004

Aims:  To study HER2 oncogene amplification and over‐expression in skin samples of 23 patients with extramammary Paget's disease (EMP). EMP is a rare intra‐epidermal adenocarcinoma, which has been reported to over‐express the HER2 oncoprotein.Methods and results:  HER2 gene amplification, detected by chromogenic in‐situ hybridization, was found in 43% (10/23) of the lesions. HER2 protein over‐expression (3+ immunostaining intensity) was found in 12 tumours (52%), including all 10 tumours with gene amplification. Two tumours showed low‐level (2+) HER2 immunostaining. Mammary Paget's lesions, which were used as controls, showed HER2 amplification and over‐expression in all 10 cases studied.Conclusions:  These results indicate that HER‐2 protein over‐expression in EMP is common and due exclusively to gene amplification. They open up the possibility of HER2‐targetted immunotherapy for patients with HER2+ disease.
Calponin and h‐caldesmon expression in synovial sarcoma; the use of calponin in diagnosis
Authors: Fisher C , Montgomery E , Healy V 
Published: December 2004

Aims:  To assess the frequency of expression and potential diagnostic utility of calponin and caldesmon in synovial sarcomas.Methods and results: Immunohistochemistry with antibodies to calponin and h‐caldesmon was undertaken in paraffin sections from 50 synovial sarcomas (19 biphasic and 31 monophasic, of which one biphasic and eight monophasic tumours had poorly differentiated areas), 10 each of malignant peripheral nerve sheath tumour (MPNST), solitary fibrous tumour (SFT), dermatofibrosarcoma (DFSP), Ewing's sarcoma (ES/PNET), and neuroblastoma, eight alveolar rhabdomyosarcomas, five adult fibrosarcomas and five carcinosarcomas. Nine of 19 biphasic synovial sarcomas were positive for calponin in spindle and glandular areas, nine in spindle cells only, and one in glands only. All monophasic synovial sarcomas and poorly differentiated areas expressed calponin; in monophasic tumours this was focally (29% of cases), moderately (39%), or diffusely (32%) positive and the poorly differentiated areas were usually moderately or diffusely positive. Four synovial sarcomas showed focal reactivity for h‐caldesmon. Calponin was found in 4/10 MPNST, 7/10 SFT, 4/10 DFSP, 3/5 fibrosarcomas and the spindle component of the carcinosarcomas. H‐caldesmon was weakly positive in 1/10 MPNST, 4/10 SFT, 0/10 DFSP, 0/5 fibrosarcomas and 1/5 carcinosarcomas (glands only). Both markers were negative in the other small round cell tumours.Conclusions: Calponin can be used as an additional marker for synovial sarcoma. Its absence argues against the diagnosis. The presence of calponin might be useful in distinguishing poorly differentiated synovial sarcoma from other small round cell tumours. H‐caldesmon is not helpful in diagnosis of synovial sarcoma.