bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3
Authors: Rubbia‐Brandt L , Leandro G , Spahr L , Giostra E , Quadri R , Malé P J , Negro F 
Published: March 2003

Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3 Aims: To identify factors associated with liver steatosis in chronic hepatitis C. Methods and results: Occurrence and severity of liver steatosis in 254 chronic hepatitis C patients were compared with presence of alcohol abuse, body mass index (BMI) >26, history of intravenous drug addiction and hepatitis C virus (HCV) genotype. Steatosis was found in 109 (43%) patients. The occurrence of steatosis was significantly associated with ongoing alcohol abuse (P=0.03) or HCV genotype 3 (P= 0.003), but not with BMI >26. A moderate to severe steatosis was present in 60% of patients infected with HCV genotype 3, irrespective of the presence of alcohol abuse, BMI >26 or history of intravenous drug addiction. Using a multivariable stepwise logistic regression analysis, infection with genotype 3 had an odds ratio (OR) of 10 (95% confidence interval (CI)=4.56–22) for a liver steatosis, whereas the presence of a cirrhosis at histology had an OR=0.256 (95% CI=0.07–0.92). Conclusions: A moderate to severe degree of steatosis of the liver is a morphological sign suggestive of infection with HCV genotype 3, independent of other risk factors of a fatty liver, but it may disappear at late stages of the disease.
Cytokeratin 14 immunoreactivity distinguishes oncocytic tumour from its renal mimics: an immunohistochemical study of 63 cases
Authors: Chu P G , Weiss L M 
Published: March 2003

Cytokeratin 14 immunoreactivity distinguishes oncocytic tumour from its renal mimics: an immunohistochemical study of 63 cases Aims: The cytokeratin 14 (CK14) expression in oncocytomas or oncocytic tumours of various tissue origins has not been established. We have studied CK14 expression in 30 cases of oncocytic tumours of various tissue origins and 33 cases of renal cell carcinoma with overlapping features (mimics) by immunohistochemistry. Methods and results: Immunohistochemistry (ABC–HRP method) was performed for detection of CK14 in 30 cases of oncocytic tumour and 33 cases of renal mimics. To demonstrate CK14 specificity and sensitivity in oncocytic tumours, mES‐13 (an anti‐mitochondrial monoclonal antibody) immunohistochemistry was also performed in 20 of 30 cases on oncocytic tumour and all 33 cases of renal mimics. We found that all 30 cases of oncocytic tumour showed cytoplasmic CK14 positivity. All 20 cases of oncocytic tumour studied with mES‐13 were positive. CK14 immunoreactivity was identified in only four cases of renal cell carcinoma (one conventional renal cell carcinoma with granular cytoplasm and three chromophobe renal cell carcinomas with eosinophilic cytoplasm). In contrast, all 33 cases of renal cell carcinoma were positive for mES‐13 to varying degrees. Conclusion: The homogeneous, cytoplasmic, and granular CK14 immunoreactivity is sensitive and specific for oncocytic tumours, whereas CK14 immunoreactivity in renal mimics is light and sporadic with peripheral accentuation.
Secondary malignant giant‐cell tumour of bone: molecular abnormalities of p53 and H‐ras gene correlated with malignant transformation
Authors: Oda Y , Sakamoto A , Saito T , Matsuda S , Tanaka K , Iwamoto Y , Tsuneyoshi M 
Published: March 2003

Secondary malignant giant‐cell tumour of bone: molecular abnormalities of p53 and H‐ras gene correlated with malignant transformation Aims: We report two cases of secondary malignant giant‐cell tumour occurring without irradiation therapy. To elucidate the mechanism of malignant transformation in this tumour, we searched for the molecular abnormalities of p53, MDM2 and the H‐ras genes. Methods and results: These cases were retrieved after a review of 103 cases of primary giant‐cell tumour of bone, registered in our institute. One case occurred in the distal femur of a 42‐year‐old female after surgical curettage, while the other arose in the acetabulum of a 25‐year‐old male after en bloc resection. Microscopically, the malignant tumour in the distal femur was composed of a proliferation of ovoid or fusiform cells arranged in fascicles with high mitotic activities. The malignant transformed tumour in the acetabulum was made up of pleomorphic tumour cells with atypical mitoses. In the tumour of the distal femur, both p53 and H‐ras mutations were detected. Abnormal nuclear accumulation of p53 protein and c‐myc expression were also revealed by immunohistochemistry. In both cases, the recurrent malignant tumour over‐expressed MMP‐9 and revealed a higher MIB‐1‐labelling index compared with the primary conventional giant‐cell tumour. Conclusions: Our results suggest that multiple oncogene or tumour suppressor gene mutations may play an important role during malignant transformation in conventional giant‐cell tumours.
Patterns of episialin/MUC1 expression in endometrial carcinomas and prognostic relevance
Authors: Sivridis E , Giatromanolaki A , Koukourakis M I , Georgiou L , Anastasiadis P 
Published: March 2003

Patterns of episialin/MUC1 expression in endometrial carcinomas and prognostic relevance Aims: To investigate episialin/MUC1 expression in the normal, hyperplastic and neoplastic endometrium, and relate patterns of tumour MUC1 reactivity with histopathological characteristics, oestrogen and progesterone receptor (ER and PR) status, bcl‐2 and p53 oncoproteins and with clinical behaviour. Methods and results: We studied 42 normally cycling endometria, 45 endometrial hyperplasias of various forms, and 111 endometrial carcinomas of endometrioid and non‐endometrioid cell types with specific monoclonal antibodies employing standard immunohistochemical techniques. The follow‐up period ranged from 34 to 182 months with a median of 86 months. Epithelial mucin episialin/MUC1 was consistently expressed in the normal endometrium, following a cyclical pattern: ‘apical membrane staining’ in early and mid‐proliferative endometrium; ‘purely cytoplasmic staining’ in late proliferative endometrium; and ‘cytoplasmic staining with intraluminal secretions’ in secretory endometrium. Immunostaining patterns in simple and complex hyperplasia were similar to late proliferative endometrium, while atypical hyperplasias and endometrial carcinomas either simulated patterns of proliferative endometrium or lacked MUC1 reactivity. Membranous MUC1 positivity was statistically more frequent in endometrioid carcinomas compared with carcinomas of non‐endometrioid type (P = 0.006). Cytoplasmic MUC1 positivity was significantly associated with poor prognosis, while MUC1‐negative carcinomas were associated with PR expression and an improved survival (P=0.04). There was no association of MUC1 patterns with bcl‐2 and p53 immunoreactivity or with other histopathological variables. Conclusions: Episialin/MUC1 is an integral component of the normal premenopausal endometrium and is probably hormonally regulated. It is frequently expressed in endometrial hyperplasias and carcinomas. The loss of MUC1 expression from endometrial carcinomas is associated with a favourable prognosis.
Secretory carcinoma of the breast: a tumour analogous to salivary gland acinic cell carcinoma?
Authors: Hirokawa M , Sugihara K , Sai T , Monobe Y , Kudo H , Sano N , Sano T 
Published: March 2003

Secretory carcinoma of the breast: a tumour analogous to salivary gland acinic cell carcinoma? Aims: Acinic cell‐like breast carcinoma is a newly recognized entity, and few acinic cell‐like breast carcinoma cases have been reported. All reported acinic cell‐like breast carcinomas were counterparts of the solid type of acinic cell carcinoma of the salivary gland. We report here three cases of secretory breast carcinoma with acinic cell differentiation, and discuss the similarity between secretory breast carcinoma and acinic cell carcinoma of the salivary gland. Methods and results: The cases were histologically identical to acinic cell carcinoma of the salivary gland: papillary‐cystic type in case 1, a mixture of papillary‐cystic, microcystic and follicular type in case 2, and microfollicular type in case 3. Immunohistochemically, the tumour cells were positive for salivary‐type amylase, lysozyme, S100 protein and α1‐antitrypsin, and negative or less reactive for gross cystic disease fluid protein‐15 and oestrogen receptor. All three cases did not reveal metastasis or recurrence. Conclusions: These cases were typical of secretory breast carcinoma, and were clinically, histologically and immunohistochemically analogous to acinic cell carcinoma of the salivary gland. We emphasize that secretory breast carcinoma and acinic cell carcinoma of the salivary gland may be identical lesions.
How should we grade CIN?
Authors: Heatley M K 
Published: March 2003

How should we grade CIN? The grading of cervical intraepithelial neoplasia (CIN) is problematic. CIN represents a morphological continuum, but biopsies displaying this lesion are classified into two (e.g. Bethesda) or three grade categories, sometimes with poor reproducibility. There are also difficulties in reliably distinguishing low‐grade CIN from its reactive simulants. Because of problems with inter‐ and intra‐observer disagreement in the grading of CIN and the diagnosis of low‐grade lesions, three expert contributions were commissioned to address the question `how should we grade CIN?'.
Clinicopathological significance of the `keloid‐like' collagen and myxoid stroma in advanced rectal cancer
Authors: Ueno H , Jones A , Jass J R , Talbot I C 
Published: March 2003

Clinicopathological significance of the `keloid‐like' collagen and myxoid stroma in advanced rectal cancer Aim: To establish the histological categorization of fibrotic stroma which reflects the biological behaviour of advanced rectal cancer. Methods and results: Six hundred and twenty‐seven surgically resected cases of advanced rectal carcinoma were examined. We histologically categorized fibrotic stroma in the invasive frontal region into three groups: type A, multiple fine and mature fibres were stratified into layers; type B, broad bands of eosinophilic hyalinized collagen (`keloid‐like' collagen) were intermingled; type C, myxoid stroma. Type A stroma was observed in 63% of patients, type B stroma in 25%, type C stroma in 12%. The incidence of type A stroma decreased in accordance with Dukes stage (98% in Dukes A; 73% in B; 41% in C1; 29% in C2) and conversely, there was an increase of C type (0% in Dukes A; 4% in B; 20% in C1; 54% in C2). Stroma type had a significant correlation with long‐term survival (80% of 5‐year survival in type A stroma; 54% in type B; 26% in type C). Based on multivariate analysis, it was found that the stromal pattern had independent prognostic value, together with nodal involvement, growth pattern, and lymphocyte infiltration. Conclusions: Tumour fibrotic stroma may play an important role as a regulator of neoplastic behaviour. Pathological categorization of the fibrotic stroma is helpful for predicting the prognostic outcome of patients with rectal carcinoma.
Recent advances in immunohistochemistry in gynaecological pathology
Authors: McCluggage W G 
Published: March 2003

Recent advances in immunohistochemistry in gynaecological pathology Recent years have witnessed significant developments in the use of immunohistochemistry in diagnostic gynaecological pathology. This review details the most significant of these. In ovarian pathology, differential cytokeratin staining (CK7 and 20) assists in distinguishing between a primary ovarian adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin. The development of markers characteristic of ovarian sex cord‐stromal tumours (especially α‐inhibin) facilitates diagnosis of these neoplasms which is often difficult by morphology alone due to the wide differential diagnosis. In the uterus, the distinction between a primary endometrial and endocervical adenocarcinoma may be facilitated by use of a small panel of antibodies, including CEA, ER and vimentin. Newly developed antibodies such as CD10 and h‐caldesmon may be of use in the diagnosis of uterine mesenchymal lesions, especially in the distinction between endometrial stromal and smooth muscle lesions. Proliferation markers, such as MIB1, are of value in the cervix in the diagnosis of preinvasive squamous and glandular lesions. Recent studies have shown that cervical adenoma malignum exhibits a gastric phenotype. Advances have also been made in trophoblastic disease with the development of antibodies reactive against trophoblast such as α‐inhibin, mel‐Cam and p57. A newly developed monoclonal antibody HMGIC which is expressed in vulvovaginal aggressive angiomyxoma may prove to be of value in the often difficult distinction of this lesion from its histological mimics.
CD34+ stromal cells and hyalinized vascular changes in the anal fibroepithelial polyps
Authors: Sakai Y , Matsukuma S 
Published: March 2003

Aims:  To elucidate the pathogenesis of the anal fibroepithelial polyp, we examined surgically resected lesions histopathologically.Methods and results:  Twenty‐seven surgically resected anal fibroepithelial polyps were investigated histologically with an additional immunohistochemical examination using anti‐CD34. For a control study, the surgical specimens of the anal canal showing non‐polypoid lesions, obtained from haemorrhoidectomy (18 specimens) and rectectomy (five specimens) due to rectal cancer without anal canal involvement, were also analysed. We demonstrated characteristic spindle or stellate cells immunohistochemically positive for CD34 in the anal fibroepithelial polyps (24/27, 89%). The number of CD34+ cells was statistically related to the size of anal fibroepithelial polyps, although CD34+ stromal cells were recognized in the non‐polypoid anal submucosa and haemorrhoids. We also found hyalinized vascular changes in the base of six anal fibroepithelial polyps examined. These features were not detected in the non‐polypoid anal canal.Conclusions:  An increase in CD34+ stromal cells may play a role in the enlargement of anal fibroepithelial polyps. CD34+ stromal cells are suggested to be distinctive mesenchymal cells with a capability for tissue repair and overgrowth. The vascular impairment could be secondary change associated with localized tissue damage by abnormal traction.
Prognostication of invasive ductal breast cancer by quantification of E‐cadherin immunostaining: themethodology and clinical relevance
Authors: Elzagheid A , Kuopio T , Ilmen M , Collan Y 
Published: March 2003

Prognostication of invasive ductal breast cancer by quantification of E‐cadherin immunostaining: the methodology and clinical relevanceAims:  We tried to improve the evaluation of E‐cadherin immunostaining in paraffin sections, to distinguish the less aggressive variants of ductal infiltrating breast cancer from other variants.Methods and results:  The method graded the membrane staining and estimated the fraction of area of cancer tissue stained at the respective staining grade, resulting in an immunohistochemical staining index. At the cut‐point 0.35 the index divided all 157 patients (P=0.0188), and 57 node‐positive patients (P= 0.0006) into two groups of different survival. In multivariate analysis (all patients) E‐cadherin immunoscore was inferior to mitotic index (SMI) (P=0.0002), but still significant (P=0.0031). Among node‐positive patients E‐cadherin was even more powerful and superior (P=0.0001) to the still significant SMI (P=0.0023), and E‐cadherin immunostaining and the mitotic activity (SMI) combined did not need the support of other prognosticators in the Cox model.Conclusions:  The study suggests that E‐cadherin immunostaining can be used efficiently in finding patients with favourable outcome among node‐positive patients.
Alteration of PTEN expression in endometrial carcinoma is associated with down‐regulation of cyclin‐dependent kinase inhibitor, p27
Authors: An H‐J , Lee Y‐H , Cho N‐H , Shim J‐Y , Kim J‐Y , Lee C , Kim S‐J 
Published: March 2003

Aims:  PTEN is a recently identified tumour suppressor inactivated in a wide variety of human cancers, including endometrial cancers. Mutation of the PTEN tumour suppressor gene has been reported in approximately 50–83% of endometrial adenocarcinoma. Despite this fact, study of the expression of PTEN protein in human tumours is limited. PTEN protein functions as a tumour suppressor by regulating the cell cycle and survival through signal transduction pathway. PTEN protein was considered to have a dual‐specificity phosphatase activity, but it is now known that its principal physiological activity is mainly derived from its lipid phosphatase activity. The cyclin‐dependent kinase inhibitor, p27, has been suggested as a downstream target of cell cycle arrest of PTEN in various in vitro studies. In this study, we evaluated the alteration of PTEN protein expression in endometrial carcinoma and assessed its relationship to the expression of p27, the presumed downstream target of PTEN.Methods and results:  Immunohistochemical staining was performed on 66 cases of endometrial carcinoma including 61 endometrioid type and five serous type, using antibodies to PTEN and p27. Loss or decrease of PTEN expression was observed in 66% (40/61 cases) of uterine endometrioid carcinoma, whereas most uterine serous carcinoma (4/5 cases) showed intense PTEN expression. Four (30%) of 13 endometrial hyperplasia synchronous with endometrioid carcinoma demonstrated complete loss of PTEN expression. All endometrioid carcinoma synchronous with PTEN‐negative endometrial hyperplasia showed loss of PTEN expression. Alteration of PTEN expression was not correlated with histological grade or stage. Decreased immunoreactivity of p27 was found in 48 cases (79%) of 61 endometrioid carcinoma, and 76% (36 cases) of them also showed loss or decrease of PTEN expression. Four of five uterine serous carcinoma revealed strong p27 immunoreactivity, all of which showed intense PTEN expression. A positive correlation between PTEN and p27 expression was statistically significant (Mantel–Haenszel χ2 test, P=0.001). Immunoreactivity of p27 was not related to histological grade and clinical stage.Conclusion:  These results show that PTEN and p27 are differentially expressed in endometrioid type carcinoma compared with those of the serous type, and suggest that the cyclin‐dependent kinase inhibitor, p27, is a downstream target of PTEN‐dependent cell cycle arrest in endometrial carcinoma.
Immunohistochemical expression of CD10 and t(14;18) chromosomal translocation may be indicators of follicle centre cell origin in nodal diffuse large B‐cell lymphoma
Authors: McCluggage W G , Catherwood M , Alexander H D , McBride H A , Smith M E F , Morris T C M 
Published: March 2003

Aims:  Although diffuse large B‐cell lymphoma is categorized as a distinct entity in the REAL classification of lymphomas, it represents a heterogeneous group of neoplasms. A subgroup is probably of follicle centre cell origin and may evolve from a pre‐existing follicular lymphoma. The t(14;18) chromosomal translocation can be demonstrated in the majority of follicular lymphomas and the aim of this study was to investigate the prevalence of t(14;18) translocation in a series of de novo nodal diffuse large B‐cell lymphomas. We correlated this with the immunohistochemical expression of CD10, bcl2 and bcl6, markers which are usually expressed by the neoplastic cells in follicular lymphomas. We also correlated these parameters with the presence or absence of p53 protein expression by the neoplastic cells.Methods and results:  Nodal diffuse large B‐cell lymphomas (n=34) were stained immunohistochemically with monoclonal antibodies to CD10, bcl2, bcl6 and p53 (D07). Polymerase chain reaction (PCR) for the t(14;18) translocation was also performed. Fourteen, 24 and 29 (41%, 71%, 85%) cases exhibited positivity for CD10, bcl2 and bcl6, respectively. In 12 cases there was positivity with D07 (35%). By PCR, the t(14;18) translocation was identified in five cases (15%), four of which were positive for CD10 and bcl2 and all of which were positive for bcl6. One of five cases positive for the chromosomal translocation exhibited positivity with D07.Conclusions:  In this study the t(14;18) translocation was identified in 15% of diffuse large B‐cell lymphomas, all but one of which exhibited positivity for CD10, bcl2 and bcl6. These may represent cases of follicle centre cell origin which may or may not have evolved from a pre‐existing follicular lymphoma. It is possible that positivity for CD10 especially may identify cases which are of follicle centre cell origin and that the absence of t(14;18) translocation in some of these cases may reflect the fact that the translocation cannot normally be demonstrated in all follicular lymphomas. Whether the presence or absence of the translocation and the immunophenotype are prognostically important should be investigated further.
34βE12 expression along the whole spectrum of neuroendocrine proliferations of the lung, from neuroendocrine cell hyperplasia to small cell carcinoma
Authors: Sturm N , Rossi G , Lantuéjoul S , Laverrière M‐H , Papotti M , Brichon P‐Y , Brambilla C , Brambilla E 
Published: March 2003

Aims:  Monoclonal antibody 34βE12 (Ck34βE12) recognizes a set of cytokeratins (1, 5, 10, 14) expressed in normal stratified squamous epithelium. We have recently reported its expression in squamous cell carcinoma and basaloid carcinoma, in contrast to large cell neuroendocrine carcinoma, an entity with overlapping morphological features with basaloid carcinoma. We have now examined the role of Ck34βE12 in discriminating between neuroendocrine and non‐neuroendocrine proliferations.Methods and results:  We performed an immunohistochemical study of 228 cases, comprising the whole spectrum of lung neuroendocrine proliferations and tumours. All cases of neuroendocrine cell hyperplasia (n = 15), tumorlet (n = 23), typical carcinoid (n = 27) and atypical carcinoid (n = 23) were completely negative for Ck34βE12. Although the neuroendocrine cells of small cell lung carcinoma and large cell neuroendocrine carcinoma were consistently negative, a strong and diffuse positive staining was found in the non‐neuroendocrine components of combined small cell carcinoma (three of eight cases) and combined large cell neuroendocrine carcinoma (11 of 12 cases). In addition, scattered Ck34βE12+ cells were noted in 11 of 64 (17%) large cell neuroendocrine carcinoma and in seven of 56 (12.5%) small cell carcinoma, which were not obviously histologically combined. This heterogeneity of high‐grade neuroendocrine tumours was not observed in carcinoids which lack Ck34βE12 clusters of reactive cells. There was mutual exclusion between expression of neuroendocrine markers and that of Ck34βE12.Conclusion:  We conclude that 34βE12 expression excludes the neuroendocrine nature of tumour cells and uncovers the real frequency of combined forms in high‐grade neuroendocrine tumours.