bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic relevance of estimates of proliferative activity in early breast cancer
Authors: Offersen B V , Sørensen F B , Knoop A , Overgaard J 
Published: December 2004

Aims:  Immunohistochemical estimates of cell proliferation evaluated with MIB‐1 antibody have been suggested as prognostic indicators in different types of carcinoma. This study investigates whether MIB‐1 scores add additional prognostic impact when evaluated together with classical clinicopathological parameters at diagnosis in early breast cancer patients.Materials and methods:  Tumour specimens from 365 consecutively treated breast cancer patients were immunostained for MIB‐1 and evaluated under the microscope using systematic random sampling accomplished by the CAST‐grid system.Results:  The systematic random sampling technique resulted in MIB‐1 estimates with very high interobserver and intraobserver reproducibilities (P < 0.0001). Median MIB‐1 was 16% (range 0–83%). Patients were stratified by MIB‐1 in tertiles, and increasing MIB‐1 was significantly associated with poor overall and disease‐specific survival in node‐positive patients, but not in node‐negative patients. High MIB‐1 was significantly related to large tumour size, and strongly associated with high grade, high mitotic score, negative oestrogen receptor status and young age. In multivariate analysis, both with and without malignancy grade and number of mitoses included in the analysis, MIB‐1 estimates showed no independent prognostic impact.Conclusions:  High MIB‐1 estimates did not add independent prognostic information at diagnosis when evaluated together with classical prognostic markers of early breast cancer.
Glutamate‐L‐cysteine ligase in breast carcinomas
Authors: Soini Y , Karihtala P , Mäntyniemi A , Turunen N , Pääkkö P , Kinnula V 
Published: December 2004

Aims : To investigate the immunohistochemical expression of the catalytic and regulatory subunits of γ‐glutamyl cysteine synthetase, i.e. glutamate‐L‐cysteine ligase (GLCL) in 274 invasive and in‐situ breast carcinomas. GLCL is the rate‐limiting enzyme in glutathione synthesis, which is one of the most important intracellular antioxidants participating in the detoxification reactions of several cytotoxic drugs.Methods and results : In the tumour cells GLCL reactivity was observed in 50% and 44% of the cases for the catalytic and the regulatory subunits, respectively. There was a statistically significant association between their expression (P = 0.002). Lobular invasive carcinomas expressed the catalytic and regulatory subunits more often than other tumours (P = 0.050 and P = 0.046, respectively). Also in‐situ carcinomas expressed the catalytic subunit more often (P = 0.005). Tumours showing no immunoreactivity for the catalytic subunit had axillary metastases significantly more often (P = 0.013). Patients with tumours showing positivity for either subunit or both had a better survival (P = 0.037). No difference in survival could be observed between GCLC‐positive or ‐negative cases in the subgroup receiving chemotherapy.Conclusions : Expression of the catalytic and regulatory subunits of GLCL is found in a substantial number of breast carcinomas and their expression is more pronounced in lobular invasive and in‐situ carcinomas. Even though the overall expression of GLCL was associated with improved survival, no such effect was observed separately in the group receiving chemotherapy.
Osteopontin: correlation with interstitial fibrosis in human diabetic kidney and PI3‐kinase‐mediated enhancement of expression by glucose in human proximal tubular epithelial cells
Authors: Junaid A , Amara F M 
Published: December 2004

Aims : To examine the expression and localization of osteopontin (OPN), a secreted phosphoprotein implicated in the development of tubulointerstitial inflammation in various models of renal disease, in human diabetic kidneys, and to study the regulation of OPN expression in primary cultures of human renal proximal tubular epithelial cells (RPTEC).Methods and results : Differential gene expression profiling through subtractive hybridization demonstrated increased renal OPN mRNA expression in a patient with diabetic nephropathy. Immunohistochemical staining of normal and diabetic human kidney samples confirmed that OPN was localized to cortical tubular, interstitial and juxtaglomerular compartments. Quantification of OPN immunostaining revealed a marked increase in the percentage of OPN‐positive tubular profiles in diabetic kidneys (47 ± 9% versus 5 ± 3%, diabetic versus minimal change disease) that correlated strongly with the degree of cortical scarring (r2 = 0.91). Results of Northern hybridization, flow cytometry and Western blotting indicated that glucose up‐regulates OPN mRNA and protein expression in primary cultures of human RPTECs. This effect was independent of the osmotic effects of glucose and independent of insulin. Finally, glucose‐stimulated OPN expression was inhibited by LY294002, an inhibitor of phosphatidylinositol 3‐kinase activity, in a dose‐dependent manner.Conclusions : OPN is expressed in human diabetic kidneys and regulation of OPN expression is via a glucose‐mediated, phosphatidylinositol 3‐kinase‐dependent pathway.
Thymic carcinoma: a clinicopathological and immunohistological study of 19 cases
Authors: Chalabreysse L , Etienne‐Mastroianni B , Adeleine P , Cordier J‐F , Greenland T , Thivolet‐Bejui F 
Published: December 2004

Aims:  To study 19 cases of primary thymic carcinoma in order to define the clinicopathological features and the precise histochemical profile of this rare and heterogeneous group of tumours of the anterior mediastinum.Methods and results:  The study group consisted of 13 males and six females, with a mean age of 58.5 years (range 29–75 years). Superior vena cava syndrome and chest pain were the main presenting symptoms. Three patients were asymptomatic. No patient had myasthenia gravis. Six different histological types were identified: neuroendocrine tumours (six patients), epidermoid carcinoma (five patients), sarcomatoid carcinoma (three patients), lymphoepithelioma‐like carcinoma (two patients), mucoepidermoid carcinoma, clear cell carcinoma, and undifferentiated carcinoma (one patient each). The clear cell carcinoma was associated with a thymic cyst. No association with thymoma was observed. Surgical resection, performed in 10 cases, was complete in two. Sixteen patients received thoracic radiation, and 11 received systemic chemotherapy. Follow‐up information was available in 16 cases; 12 patients presented with local or metastatic relapse, and 10 patients died of their tumour. The overall 5‐year survival was 14.5%.Conclusion:  Primary thymic carcinoma is a very heterogeneous group of tumours of the anterior mediastinum with an aggressive clinical behaviour, and a poor overall prognosis.
Angiogenesis and extracellular matrix remodelling in bronchioloalveolar carcinomas: distinctive patterns in mucinous and non‐mucinous tumours
Authors: Guedj N , Couvelard A , Arcangeli G , Dubois S , Thabut G , Lesèche G , Fournier M , Degott C , Groussard O 
Published: December 2004

Aim:  Bronchioloalveolar carcinomas (BACs) are rare primitive lung adenocarcinomas growing along the alveolar septum without stromal, vascular or pleural invasion. We report an immunohistochemical study of their vascular microenvironment.Methods and results:  In three mucinous BACs (M‐BAC) and three non‐mucinous BACs (NM‐BAC) we examined the following parameters in comparison with the normal lung: (i) constituents of the alveolar extracellular matrix; (ii) qualitative and quantitative changes of alveolar capillaries; and (iii) expression of vascular endothelial growth factor (VEGF) by tumour cells. In M‐BAC, the alveolar matrix was unchanged compared with the normal parenchyma. Capillaries expressed normal alveolar endothelial markers and their average surface was calculated, as in normal lung, as 8%. VEGF was negative in tumour cells. In NM‐BAC, the alveolar wall was thickened by deposits of fibronectin and type III collagen containing myofibroblasts and the basement membrane was disrupted. Capillaries did not retain alveolar endothelial markers and their surface was calculated as 19%. Tumour cells expressed high levels of VEGF.Conclusions:  In contrast to NM‐BAC, M‐BAC do not modify the alveolar structure and seem to exploit the normal alveolar vascular bed to grow, without inducing neoangiogenesis. A better understanding of the mechanisms of growth of lung cancers may have implications for future anti‐angiogenic therapeutic strategies.
Extranodal follicular lymphoma: a clinicopathological and genetic analysis of 15 cases arising at non‐cutaneous extranodal sites
Authors: Goodlad J R , MacPherson S , Jackson R , Batstone P , White J ,   on behalf of the Scotland & Newcastle Lymphoma Group
Published: December 2004

Aims:  Recent studies of primary cutaneous follicular lymphoma suggest that it represents a clinicopathological entity distinct from nodal follicular lymphoma (FL). The purpose of this study was to determine if FL arising at other extranodal sites is more closely related to FL occurring in the skin or in lymph nodes.Methods and results:  Fifteen cases of non‐cutaneous extranodal follicular lymphoma (ENFL) were identified from the Scotland and Newcastle Lymphoma Group (SNLG) database. All were stage 1E at presentation and involved the tonsil (n = 3), palate (n = 3), skeletal muscle (n = 2), ileum (n = 2), duodenum (n = 1), stomach (n = 1), thyroid gland (n = 1), submandibular gland (n = 1) and fallopian tube (n = 1). Polymerase chain reaction for t(14;18) using primers to the major breakpoint cluster region was performed on 14 cases of ENFL and the incidence of the translocation compared with that found in 16 cases of stage 1 nodal FL. Clinical and follow‐up data were obtained from the SNLG database for the 15 cases of ENFL and 87 cases of stage 1 nodal FL, and a comparison of outcomes made. Only 2/14 cases of ENFL had detectable t(14;18) compared with 9/16 stage 1 nodal FL (P < 0.01). Freedom from progression and disease‐specific survival was similar for the 15 cases of ENFL and 87 cases of stage 1 nodal FL. However, 13/15 patients with ENFL were disease free at the end of follow‐up compared with 49/87 stage 1 nodal FL (P < 0.02).Conclusions:  The low incidence of t(14;18) and favourable outcome encountered in ENFL in this study is similar to that previously found for primary cutaneous FL. These results support the concept of a subtype of FL lacking t(14;18) involving the major breakpoint cluster region, and with a propensity to arise at extranodal sites. Despite a high relapse rate, patients with ENFL are more likely to achieve complete remission and may ultimately have a more favourable long‐term prognosis than those with equivalent nodal disease.
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

Spring 2004 Symposium on Dermatopathology. Brussels, Belgium10–15 October 2004 XXVth International Congress. Brisbane, Australia26–27 November 2004 Symposium on Pulmonary Pathology. London, UK
Non‐alcoholic duct destructive chronic pancreatitis: a histological, immunohistochemical and in‐situ apoptosis study of 18 cases
Authors: Youssef N , Petitjean B , Bonte H , Terris B , De Saint Maur P P , Fléjou J‐F 
Published: December 2004

Aims:  To assess retrospectively pancreatic changes in non‐alcoholic duct‐destructive chronic pancreatitis and to investigate the role of apoptosis in duct destruction.Methods and results:  Eighteen patients (mean age 46 years, nine women and nine men) underwent pancreatic resection for suspected pancreatic tumour and were diagnosed as having non‐alcoholic duct‐destructive chronic pancreatitis. We performed a morphological study either semiquantitatively (fibrosis and inflammation) or quantitatively (CD3+ intraepithelial lymphocytes, M30 and TUNEL+ apoptotic cells). The results were compared with those obtained in 10 cases of chronic alcoholic pancreatitis and nine cases of chronic obstructive pancreatitis. Pancreatic changes were diffuse and heterogeneous in 14 cases, but segmental in four cases. The main pancreatic lesions were ductal epithelial alteration, periductal inflammation and fibrosis. There were no cysts or calcifications. We found a marked increase in mast cells in the infiltrate, a slight increase in TiA1+ lymphocytes and in intraepithelial lymphocytes compared with other types of chronic pancreatitis. No significant increase in ductal apoptosis was observed.Conclusion:  Non‐alcoholic duct‐destructive chronic pancreatitis is a well‐defined pathological entity, distinct from alcoholic and obstructive chronic pancreatitis. Our results indicate that apoptosis probably does not play a major role in ductal alterations.
NK and NK‐like T‐cell lymphoma in extranasal sites: a comparative clinicopathological study according to site and EBV status
Authors: Ko Y H , Cho E‐Y , Kim J‐E , Lee S‐S , Huh J‐R , Chang H‐K , Yang W‐I , Kim C‐W , Kim S‐W , Ree H J 
Published: December 2004

Aims:  To analyse the clinicopathological findings of extranasal CD56+ cytotoxic T‐ or NK‐cell lymphomas in different organs and to compare Epstein–Barr virus (EBV)+ and EBV– lymphoma of non‐blastoid cytomorphology.Methods and results:  Fifty‐one cases of cCD3+ T‐cell intracellular antigen (TIA‐1)+ CD56+ lymphomas of extranodal/extranasal origin were included in the study. The primary sites of the CD56+ tumours were soft tissue (n = 10), the gastrointestinal (GI) tract (n = 13), the skin (n = 15), upper aerodigestive tract excluding nasal and nasopharyngeal regions (n = 11), the testis (n = 1), and parotid gland (n = 1). TCR gene rearrangement was detected in seven of 47 cases examined (16%). EBV was positive in 39 of 51 cases (76%). The positive rate of EBV was higher in tumours of soft tissue (80%), GI tract (92%), and skin (80%), and lowest in the upper aerodigestive tract excluding the nasal and nasopharyngeal region (50%). Tumours of the soft tissue and the upper aerodigestive tract tended to present with localized disease (P = 0.002). The 2‐year survival rate was lowest for tumours of the GI tract (P = 0.0256). EBV– TCR– lymphoma showed less necrosis (P = 0.0133) and a better 2‐year survival rate (P = 0.0066) than EBV+ TCR– lymphoma. Patients with EBV+ TCR+ lymphomas tended to present with localized disease, more often than EBV+ TCR– lymphoma (P = 0.0186). Significant prognostic factors in all CD56+ lymphomas were the site (P = 0.0256), EBV status (P = 0.0026), necrosis with or without perforation (P = 0.0338) and the presence of pleomorphic large tumour cells (P = 0.0428). Cox's regression analysis adjusting for other pathological parameters showed EBV status to be the only independent prognostic factor (P = 0.018).Conclusions:  Extranodal CD56+ EBV– lymphoma at extranasal sites is a clinically less aggressive malignancy and displays less necrosis than CD56+ EBV+ lymphoma. Because CD56+ EBV+ TCR+ lymphomas show similar pathological and clinical findings to CD56+ EBV+ TCR– lymphomas, nasal‐type NK/T‐cell lymphomas at extranasal sites should be diagnosed as such on the basis of EBV+, cytotoxic T or NK phenotype irrespective of the genotype determined by molecular study.
Usefulness of immunohistochemistry in delineating renal spindle cell tumours. A retrospective study of 31 cases
Authors: Wang J , Weiss L M , Hu B , Chu P , Zuppan C , Felix D , Rausei‐Mills V , Chase D R 
Published: December 2004

Aims:  To assess the usefulness of immunohistochemistry in delineating tumour diagnoses on a series of morphologically diagnosed renal spindle cell tumours (RSCTs).Methods and results:  Formalin‐fixed paraffin‐embedded tissues from 31 morphologically diagnosed tumours were reinterpreted in light of newly obtained immunohistochemical information. By morphology, six had originally been classified as sarcomatoid carcinoma, five as spindle cell tumour (NOS), four as sarcoma (NOS), three as leiomyoma, three as leiomyosarcoma, and one each as fibrous polyp, hamartoma, neurilemmoma, mesoblastic nephroma, medullary fibroma, angiomyolipoma, haemangiopericytoma, malignant rhabdoid tumour, malignant Triton tumour, and carcinosarcoma. The application of immunohistochemistry verified the original diagnosis in 18 cases (18/31, 58%), confirming the diagnosis of sarcomatoid renal carcinoma (4/6), leiomyoma (2/3), leiomyosarcoma (3/3), sarcoma (NOS) (2/4), carcinosarcoma (1/1), malignant rhabdoid tumour (1/1), malignant Triton tumour (1/1), fibrous polyp (1/1), mesoblastic nephroma (1/1), hamartoma (1/1), and angiomyolipoma (1/1). Different tumour designations were suggested in 13 cases (13/31, 42%), including carcinosarcoma, sarcoma (NOS), leiomyosarcoma, solitary fibrous tumour, monomorphic/biphasic angiomyolipoma, endometrial stromal tumour, and congenital mesoblastic nephroma.Conclusions:  Our data indicate that although morphology is most important in formulating the initial differential diagnosis, the addition of immunohistochemistry is vital in arriving at the correct classification of RSCTs.
COX‐2+ myofibroblasts may play a key role in marked stromal fibrosis in strictured colorectal carcinomas
Authors: Kasamaki S , Suda K , Kamano T , Kumasaka T , Ochiai T , Haraguchi Y 
Published: December 2004

Aims:  To elucidate the mechanism of marked stromal fibrosis in strictured colorectal carcinomas (SC) that cause complete ileus.Methods and results:  Sixteen cases of SC and 29 cases of non‐strictured colorectal carcinoma (NSC) were studied. These carcinomas showed similar clinicopathological features except for bowel stricture. The stricture index (SI) showing the degree of bowel stricture was 59.8 ± 12.1% in SC versus 20.8 ± 24.6% in NSC (P < 0.001). The fibrosis index (FI), defined to reflect the extent of stromal fibrosis, was 56.3 ± 8.8% in SC versus 21.9 ± 10.6% in NSC (P < 0.001). COX‐2+ myofibroblasts were detected in 13 cases (81.3%) in SC versus eight cases (27.6%) in NSC (P < 0.01). The COX‐2+ myofibroblast density was 276.7 ± 181.1 cells/mm2 in SC versus 26.6 ± 52.7 cells/mm2 in NSC (P < 0.001). When all cases were divided into two groups with and without COX‐2+ myofibroblasts, the SI was 48.8 ± 19.1% in those with COX‐2+ myofibroblasts versus 24.8 ± 29.3% in those with COX‐2– myofibroblasts (P < 0.001).Conclusion:  COX‐2+ myofibroblasts may play an important role in extensive bowel stricture in colorectal carcinomas.
Expression of apoptosis‐regulatory proteins in lesions of pulmonary Langerhans cell histiocytosis
Authors: Marchal J , Kambouchner M , Tazi A , Valeyre D , Soler P 
Published: December 2004

Aims:  Pulmonary Langerhans cell histiocytosis (PLCH) is characterized by the presence of lesions containing numerous activated Langerhans cells (LCs). An uncontrolled immune response sustained by activated LCs seems to be involved in the pathogenesis of the disease. The aim of this study was to establish whether disruption of LC apoptosis related to the expression of the Bcl‐2 family proteins is implicated in the maintenance of PLCH lesions.Methods:  Six patients with PLCH were evaluated by morphological and immunohistochemical techniques to explore the incidence of apoptosis in pathological LCs and to characterize the expression of Bcl‐2‐related proteins by these cells.Results:  Very few LCs present in PLCH lesions exhibited nuclear apoptotic changes or expressed cleaved caspase‐3, whereas they all strongly expressed the anti‐apoptotic molecule Bcl‐xL. Interestingly, pulmonary LCs present in intervening lung tissue not involved by the pathological process and known to be immature dendritic cells did not express Bcl‐2 family proteins.Conclusions:  These findings suggest that activated LCs present within PLCH lesions are poorly susceptible to apoptosis and, thus, are able to sustain the pathological process by causing continuous local stimulation of T cells. Functional studies are needed, however, to demonstrate that they are actually resistant to programmed cell death.
Hashimoto's thyroiditis with papillary thyroid carcinoma (PTC)‐like nuclear alterations express molecular markers of PTC
Authors: Prasad M L , Huang Y , Pellegata N S , De La Chapelle A , Kloos R T 
Published: December 2004

Aims:  Focal papillary thyroid carcinoma (PTC)‐like nuclear alterations have been documented in Hashimoto's thyroiditis; however, the molecular association between PTC and Hashimoto's thyroiditis is poorly understood. The aim of this study was to determine whether molecular expression patterns of PTC are present in association with PTC‐like nuclear alterations in Hashimoto's thyroiditis.Methods and results:  The expression of four genes known to be up‐regulated in PTC [LGALS3 (galectin3), CITED1, KRT19 (cytokeratin 19) and FN1 (fibronectin‐1)] and the human mesothelial cell protein identified by monoclonal antibody HBME1 was evaluated. Immunohistochemistry was performed on 23 cases of Hashimoto's thyroiditis with focal or diffuse Hürthle cell change and PTC‐like nuclear alterations, 37 PTC and 18 normal thyroids. Focal expression of galectin3 (GAL3), CITED1, cytokeratin 19 (CK19), HBME1 and fibronectin‐1 (FN1) was seen in 87%, 65%, 43%, 26% and 17% of Hashimoto's thyroiditis, respectively, only in thyrocytes showing PTC‐like nuclear alterations. In contrast, diffuse expression of GAL3, CITED1, CK19, HBME1 and FN1 was seen in 100%, 95%, 70%, 87% and 89% of PTC, respectively. Normal thyroid tissues did not express any of these proteins. Following immunohistochemistry, four Hashimoto's thyroiditis cases were found to contain foci of PTC. These foci were highlighted by the diffuse and strong expression of PTC‐associated proteins, which prompted additional retrospective scrutiny of the haematoxylin and eosin‐stained sections leading to appreciation of complete PTC‐type nuclear atypia.Conclusions:  Focal PTC‐like immunophenotypic changes in Hashimoto's thyroiditis suggest the possibility of early, focal premalignant transformation in some cases of Hashimoto's thyroiditis.
The activation profile of tumour‐associated reactive T‐cells differs in the nodular and diffuse patterns of lymphocyte predominant Hodgkin's disease
Authors: Lin P , Medeiros L J , Wilder R B , Abruzzo L V , Manning J T , Jones D 
Published: December 2004

Aims:  To compare the activation profile of T‐cells in reactive lymphoid follicles with that of tumour‐associated T‐cells in lymphocyte predominant Hodgkin's disease (LPHD) with a nodular pattern (n = 21), LPHD with partial diffuse growth pattern (n = 11) and T‐cell‐rich large B‐cell lymphoma (TCRLBCL, n = 8).Methods and results:  Reactive germinal centres showed sparse numbers of T‐cells positive for CD134, a transient/early T‐cell activation marker, and only scattered T‐cells in the interfollicular areas positive for CD38, a marker of persistent activation. Lymphoid follicles showing progressive transformation of germinal centres (PTGC) had more numerous CD134+ T‐cells which were negative for CD38. Tumour‐associated T‐cells in nodular LPHD were frequently positive for CD134 (15 of 16 cases, 94%), but negative or only focally positive for CD38 (three of 21 cases, 14%). LPHD with diffuse areas, however, showed increased CD38+ T‐cells in the diffuse component in 10 of 11 (90%) cases, with CD134+ T‐cells being more prominent in the nodular tumour component. TCRLBCL showed strong, uniform CD38 expression in T‐cells and histiocytes in eight cases.Conclusions:  T‐cells in nodular LPHD express markers of transient/early T‐cell activation. By contrast, T‐cells in the diffuse form of LPHD, similar to those in TCRLBCL, have an immunostaining profile consistent with persistent cellular activation. T‐cell activation may precede or accompany histological progression in nodular LPHD and immunostaining for these markers, in small samples or in difficult cases, may be useful in highlighting those cases of LPHD undergoing histological progression.