bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical analysis of patients with azoospermia factor deletions by microdissection testicular sperm extraction
Authors: Tsujimura Akira , Matsumiya Kiyomi , Takao Tetsuya , Miyagawa Yasushi , Koga Minoru , Takeyama Masami , Fujioka Hideki , Okuyama Akihiko 
Published: December 2004

SummaryMicrodeletions of the azoospermia factor (AZF) locus on the Y chromosome have been implicated as a major genetic component of idiopathic male infertility, and the incidence of AZF deletions has been reported to be 15–20% in men with non‐obstructive azoospermia (NOA). Numerous studies have described AZF deletion rates in patients with azoospermia; however, a clinical comparison of azoospermic patients with AZF deletion and those with no deletion has not been reported well. A new technique for testicular sperm extraction, microdissection testicular sperm extraction (TESE), has been used widely on NOA patients. Although testicular spermatozoa are reliably detected and retrieved from NOA patients by microdissection TESE, sperm retrieval rates for patients with AZF deletions are not well known. Therefore, characteristics of NOA patients with AZF deletion were investigated. Six of 60 patients (10%) who underwent microdissection TESE were found to have AZF deletions by genomic polymerase chain reaction. Testicular data, outcome of sperm retrieval and endocrinological profiles, were compared between patients with AZF deletions (n = 6) and those with no deletions (n = 54). Testicular size, varicocele rates and testicular histology were similar between the groups. Significant differences were not detected in the endocrinological profiles. Sperm retrieval rates were not significantly different between the groups. In conclusion, AZF deletions do not appear to confer specific characteristics to NOA patients.
Effect of neonatal exposure to diethylstilbestrol on testicular gene expression in adult mouse: comprehensive analysis with cDNA subtraction method
Authors: Matsuno Yoshiharu , Adachi Tetsuya , Koh Kyu‐Bom , Fukata Hideki , Sugimura Atsushi , Sakurai Kenichi , Shibayama Takako , Iguchi Taisen , Komiyama Masatoshi , Mori Chisato 
Published: December 2004

SummaryIn utero or neonatal exposure to high levels of exogenous steroid hormones, such as the potent synthetic diethylstilbestrol (DES), incurs an increased risk of malfunctional male reproduction. In this study, we investigated whether neonatal exposure to DES induces the alteration of mRNA expression in adult mouse testis. Using a cDNA subtraction method, we isolated seven gene clones whose expression was changed in neonatally DES‐treated mouse testis. Northern blot analysis revealed that five up‐regulated genes (AF326230, AF356521, AK004975, AK006136 and BM237156) and two down‐regulated genes (AK017044, AK017130) were predominantly expressed in testes of 8‐week‐old mice. Moreover, we confirmed that the expression of these seven genes was altered by neonatal DES‐exposure using Northern blot analysis. Our results suggest that neonatal exposure to DES leads to the alteration of gene expression in the testis in the long term. These genes might be useful as biological markers of foetal or neonatal exposure to exogenous steroid hormones, such as DES.
Cellularity of human annulus tissue: an investigation into the cellularity of tissue of different pathologies
Authors: Ford J L , Jones P , Downes S 
Published: December 2004

Aims:  To investigate the cells of the inner annulus and to demonstrate that differences in disc pathology can be identified at the cellular level.Methods and results:  Annulus tissue taken from scoliotic, degenerate and prolapsed human disc tissue was processed for histology and transmission electron microscopy. Ki67 antibody was used to identify cells in the active part of the cell cycle and cell surface receptors for the matrix‐degrading enzyme urokinase were immunolocalized. More chondron clusters were observed in tissue from prolapsed discs than in degenerate and scoliotic discs. Positive Ki67 staining was detected in cells within chondron clusters. Most cells observed from scoliotic and prolapsed annulus contained distinctive nuclei and organelles, whereas cells from degenerate discs contained very few well‐defined organelles but abundant glycogen deposits. Immunolocalization identified urokinase receptors on the surface of cells from degenerate discs but not in the other pathologies.Conclusions:  Cellular differences appear to underlie different types of disc pathology. The annulus tissue taken from prolapsed discs appeared to contain more chondron clusters and more active cells than scoliotic and degenerative tissue, suggesting a possible wound repair response. In contrast, cell and matrix degeneration appeared to be the most significant underlying processes in degenerate discs.
Leiomyoblastoma of the uterus: an immunohistochemical and electron microscopic study of distinctive tumours with immature smooth muscle cell differentiation mimicking fetal uterine myocytes
Authors: Watanabe K , Ogura G , Suzuki T 
Published: December 2004

Aims:  We present three distinctive uterine tumours which exhibited immature smooth muscle differentiation mimicking smooth muscle cells of the fetal uterus.Methods and results:  The patients were 45, 46 and 49 years old, and all of them had simple hysterectomies. Grossly, all tumours were present in the uterine body, and two of the three tumours were well demarcated 60‐mm and 85‐mm lesions, and the other tumour was a small 25‐mm incidental lesion within multiple conventional leiomyomas. The tumours had varied histological features and were composed of round epithelioid, rhabdoid and large vacuolated cells intermingled with spindle‐shaped cells to various degrees. Although their round vesicular nuclei showed mild to moderate variation in size, prominent nuclear atypia was not seen. Necrosis and mitotic figures suggesting biological aggressiveness were not present in any of the tumours. Immunohistochemically, tumour cells were intensely positive for desmin and α‐smooth muscle actin, whereas positivity for heavy molecular weight caldesmon was restricted. In addition, two cases were positive for non‐muscle myosin heavy chain (SMemb). Ultrastructurally, most tumour cells contained various amounts of intermediate filaments which were occasionally abundant and aggregated as in rhabdoid cells. Well‐developed myofilaments with focal densities were observed in only a few tumour cells. Intermediate filaments and bundles of thin filaments without dense bodies were often intermingled and they occasionally formed distinctive complexes with many irregular dense body‐like structures and crystalloid bodies. Other cytoplasmic organelles including rather rich mitochondria, some rough endoplasmic reticulum and free ribosomes were also common.Conclusions:  These findings support their immature smooth muscle cell differentiation which mimics the mesenchymal cells of fetal uterus during 14–26 weeks of gestation. The term ‘uterine leiomyoblastoma’ is thought to be appropriate for describing these distinctive immature smooth muscle tumours.
Oestrogen receptor negativity as a marker for high‐grade ductal carcinoma in situ of the breast
Authors: Baqai T , Shousha S 
Published: December 2004

Aims:  To compare the morphological and immunohistochemical characteristics of oestrogen receptor (ER)‐negative and ER‐positive ductal carcinoma in situ (DCIS) of the breast, in an attempt to establish more objective criteria for the classification of DCIS.Methods and results:  Sections of 64 cases of in‐situ carcinoma of the breast were stained for ER, progesterone receptors (PgR), androgen receptors (AR), c‐erbB‐2 and p53, using the immunoperoxidase technique. The cases included 60 DCIS and four lobular carcinoma in situ (LCIS). Four DCIS lesions were associated with foci of microinvasion. The 60 DCIS cases included 31 high grade, 23 intermediate grade and six low grade. Twenty‐four DCIS cases (40%) were ER‐negative and 36 were positive. ER negativity was significantly associated with high nuclear grade (88% versus 27% for ER‐positive cases, P < 0.001), PgR negativity (100% versus 25%, P < 0.001), c‐erbB‐2 positivity (79% versus 14%, P < 0.001) and p53 positivity (58% versus 6%, P < 0.001). There was no difference between ER‐negative and ‐positive DCIS as regards AR expression, with 91% of cases in each group being AR‐positive. Of the four cases of DCIS with microinvasion, three were ER‐ and PgR‐negative, all four were c‐erbB‐2‐positive and AR‐positive and one was p53‐positive. None of the four LCIS was ER, PgR or AR‐negative and none was c‐erbB‐2‐ or p53‐positive.Conclusions:  There is a highly significant direct relationship between ER negativity in DCIS and high nuclear grade, PgR negativity and c‐erbB‐2 and p53 positivity. We suggest that immunohistological assessment of ER status may help in providing a more objective way of classifying DCIS.
Clinicopathological associations of CD44 mRNA and protein expression in primary breast carcinomas
Authors: Berner H S , Suo Z , Risberg B , Villman K , Karlsson M G , Nesland J M 
Published: December 2004

Aims:  The purpose of this study was to examine the occurrence of CD44 isoforms in breast carcinomas and their role in predicting clinical outcome.Methods and results:  Shock‐frozen tumour tissues from 110 patients with breast carcinoma were examined by immunohistochemistry using antibodies directed against CD44s, v5, v6, v7 and v3–10. In addition, 80 of these tumours were available for quantitative real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis of CD44s and CD44v6. Immunohistochemically, the positive tumours showed cytoplasmic and/or membranous staining with all antibodies. Staining results did not correlate with histological subtype, lymph node status, status of steroid receptors, tumour size or age. Neither was any correlation found for overall and disease‐free survival. Quantitative real‐time RT‐PCR of CD44s and CD44v6, however, revealed that expression of CD44v6 mRNA was significantly associated with lower pathological grade (Pearson χ2 test P = 0.009; linear‐by‐linear association P = 0.003). Linear‐by‐linear association between CD44s mRNA expression and lower pathological grade was also seen (P = 0.02). Survival analysis with the Kaplan–Meier method demonstrated that increased CD44s mRNA expression was significantly associated with both disease‐free survival and overall survival (P = 0.0185 and P = 0.0344, respectively). A similar trend for CD44v6 mRNA expression was seen in these cases, but the difference was not significant.Conclusions:  Quantitative real‐time RT‐PCR revealed clinical correlations of CD44s and CD44v6 mRNA expression in breast carcinomas while immunohistochemistry for the protein expression of CD44s and other CD44 variants did not. This contradictory result merits further studies concerning the clinical impact of CD44 molecules in breast carcinomas.
Plasmablastic lymphoma in HIV+ patients: an expanding spectrum
Authors: Chetty R , Hlatswayo N , Muc R , Sabaratnam R , Gatter K 
Published: December 2004

Aim:  To describe an unusual human immunodeficiency virus (HIV)‐associated lymphoma in uncommon sites. Plasmablastic lymphoma is a distinctive HIV‐associated tumour that was first described in the jaws and oral cavity. Only two cases (stomach and lung) have been documented in extra‐oral sites.Materials and methods:  Four cases were encountered in HIV+ patients: three in the anorectal region and one which was nasal and paranasal. The cases were routinely processed and immunohistochemistry was performed on formalin‐fixed paraffin‐embedded tissue.Results: The cases showed the typical morphological appearances of a high‐grade, blastic non‐Hodgkin's lymphoma (brisk mitotic activity and tingible body macrophages). In addition, some cells had a plasmacytoid appearance and paranuclear clearing. Immunophenotypically, the tumour cells were negative for LCA, CD20 and CD45RA. However, a small proportion of cells (5%) were immunoreactive for CD79a and the majority were positive with VS38c, indicative of plasma cell differentiation. Kappa light chain and IgG heavy chain restriction was also detected.Conclusions: Plasmablastic lymphoma may occur in extra‐oral sites and has a characteristic immunophenotype including focal expression of CD31 by the neoplastic cells. Awareness of the absence of expression of conventional B‐cell markers and its presence in unusual sites should facilitate the diagnosis of plasmablastic lymphoma in HIV+ patients.
Sporadic colorectal cancers with defective mismatch repair display a number of specific morphological characteristics: relationship between the expression of hMLH1 and hMSH2 proteins and clinicopathological features of 273 adenocarcinomas
Authors: Chapusot C , Martin L , Mungra N , Rageot D , Bouvier A M , Kopp C Bonithon , Ponnelle T , Faivre J , Piard F 
Published: December 2004

Aims:  The aim of this study was to assess the independent value of pathological criteria in the diagnosis of mismatch repair (MMR)‐defective sporadic colorectal cancers.Methods and results: Resected colorectal adenocarcinomas (n = 273) were reviewed in order to identify a number of specific morphological features of MMR‐defective carcinomas. Of the 273 cases, 35.2% were right‐sided and 5.9% were poorly differentiated. Focal extracellular mucin secretion was seen in 5.1% of cases and a stromal follicular reaction in 4.6%. The expression of the two major MMR proteins hMLH1 and hMSH2 was studied by immunohistochemistry. Carcinomas were considered deficient in the MMR system when a loss of nuclear signal in neoplastic cells was observed for one of the proteins. Such an extinction was seen in 37 of the cases (13.6%). The hMLH1 protein was the one most frequently altered (86.5%). After multivariate analysis, three independent factors were significantly associated with MMR deficiency: proximal location [odds ratio (OR) = 9.30; 95% confidence interval (CI) 2.79, 30.98], the presence of a true stromal follicular reaction (OR = 13.60; 95% CI 2.98, 62.00) and poor differentiation (OR = 8.33; 95% CI 1.63, 40.32).Conclusions: These results confirm that sporadic colorectal MMR‐defective adenocarcinomas display certain specific morphological characteristics. However, these pathological features are not sufficiently predictive and immunohistochemistry is needed to identify such tumours accurately.
p57kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles
Authors: Jun S‐Y , Ro J Y , Kim K‐R 
Published: December 2004

Aims:  To determine the utility of p57kip2 in the diagnosis of hydatidiform mole. p57kip2 protein is a cyclin‐dependent kinase inhibitor (CDKI) and is strongly paternally imprinted, being expressed from the maternal allele. It has been hypothesized that complete mole (CHM) with only the paternal genome would display reduced or nearly absent expression of p57kip2 compared to partial mole (PHM) having both paternal and maternal genomes.Methods and results:  The immunohistochemical expression of p57kip2 protein was investigated using paraffin‐embedded tissue sections in histologically unequivocal cases of CHM (n = 51), PHM (n = 7), invasive mole (n = 1), and hydropic miscarriage (n = 2), as well as in histologically undetermined cases (n = 9). In the histologically unequivocal complete and invasive moles, expression of p57kip2 was absent except for one case in which villous cytotrophoblast covering the villous stroma was positive (51/52) as well as villous stromal cells (51/52). In contrast, it was strongly and continuously expressed in both villous cytotrophoblast and stromal cells in all cases of PHM and hydropic miscarriage. Among the nine histologically undetermined cases, five cases showing p57kip2 immunopositivity and hyperploid DNA were classified as PHMs, two cases showing p57kip2 immunonegativity and hyperploidy as CHMs, and two cases with p57kip2 immunopositivity and diploid DNA as hydropic miscarriage and diploid PHM, respectively, upon review of the histopathological findings. Intermediate trophoblast forming trophoblastic columns or anchoring villi and extravillous trophoblast at the implantation site showed variable expression of p57kip2 in all gestational conditions. Maternal decidua showed diffuse and strong p57kip2 expression, whereas syncytiotrophoblast was completely negative in all cases regardless of the diagnosis.Conclusions:  In summary, p57kip2 immunostaining results correlated well with morphological features of molar pregnancies and were helpful in determining histologically equivocal cases.
Immunoreactivity of cytokeratins (CK7, CK20) and mucin peptide core antigens (MUC1, MUC2, MUC5AC) in adenocarcinomas, normal and metaplastic tissues of the distal oesophagus, oesophago–gastric junction and proximal stomach
Authors: Flucke U , Steinborn E , Dries V , Mönig S P , Schneider P M , Thiele J , Hölscher A H , Dienes H P , Baldus S E 
Published: December 2004

Aims:  Adenocarcinomas of the distal oesophagus and especially the oesophago–gastric junction have shown an increasing incidence during the last decade. Definition of subgroups according to different sites of development, histogenesis or aetiology may prove to be valuable for clinical diagnosis and treatment. Previous studies have shown differences in cytokeratin patterns between Barrett's metaplasia of the oesophagus and intestinal metaplasia in the stomach. The aim of our study was to investigate whether the expression of certain cytokeratins (CK7, CK20) and mucins (MUC1, MUC2, MUC5AC) exhibit clear‐cut patterns, thus allowing a subclassification of adenocarcinomas of the oesophago–gastric junction. The possibility of a relationship between antigen expression and the presence or absence of Barrett's metaplastic epithelium was also studied.Methods and results:  CK7, CK20, MUC1, MUC2 and MUC5AC were visualized in six adenocarcinomas of the distal oesophagus, 29 adenocarcinomas of the oesophago–gastric junction and eight adenocarcinomas of the proximal stomach. CK7, CK20 and MUC1 were strongly expressed in the great majority of all neoplasms under study, whereas MUC2 and MUC5AC were absent or only faintly detectable. CK20 exhibited a significantly stronger expression in poorly differentiated tumours (G3) and MUC1 immunoreactivity correlated with tubular and papillary versus signet‐ring cell histopathology. Other statistically significant correlations between antigens and histopathological features (pTNM stage, grading, histopathological subtype, presence/absence of Barrett's epithelium) were not observed.Conclusions:  According to our results, most adenocarcinomas of the oesophago–gastric junction show a CK7+, CK20+, MUC1+ phenotype irrespective of the presence or absence of Barrett's epithelium. The immunohistochemical data suggest a similar histogenesis of these tumours.
Radial intratumoral increase and correlation of microvessels and proliferation in solid breast carcinoma
Authors: Begum R , Douglas‐Jones A G , Morgan J M 
Published: December 2004

Aims:  To compare correlations between different morphometrically assessed measurements of tumour microvasculature and to identify those which show closest correlation with Ki67 and to examine radial intratumoral distribution of microvessels and proliferation.Methods and results:  Immunohistochemically defined microvessels and Ki67+ cells were quantified in sequential fields of 0.12 mm2 (×600) in four transects in each of five tumours. The total number of vessels (TNV) correlated more closely with proliferative activity than the numbers of vessels with a discernible lumen (TLV) and TNV decreased towards the centre of the tumour whereas TLV did not. A higher proliferative index (PI) was found at the periphery of the tumours. Comparison between transects through subjectively identified microvessel hot‐spots and non‐hot‐spot transects showed similar mean, median and peak vessel counts but showed a different distribution on χ2 analysis.Conclusions:  TNV correlates most closely with PI in breast carcinomas. There is marked variation in microvessel density and PI between fields of 0.12 mm2 but there is a significant radial reduction in both from the edge towards the centre of tumours.
Genetic imbalances with impact on survival in colorectal cancer patients
Authors: Knösel T , Schlüns K , Stein U , Schwabe H , Schlag P M , Dietel M , Petersen I 
Published: December 2004

Aims: To investigate the prognostic significance of chromosomal alterations in colorectal cancer patients. Histopathological tumour classification is still considered to be the gold standard for the characterization of solid tumours. However, it is well known that such established parameters do not satisfactorily predict the clinical outcome in individual cases. Markers that reliably predict survival are needed. These markers should guide the clinical treatment of neoplastic disease.Methods and results: Chromosomal imbalances in 61 colorectal carcinoma specimens in 37 patients determined by comparative genomic hybridization were correlated with patient survival using custom‐made computer software which enabled the assessment of individual chromosomal loci. Kaplan–Meier analysis revealed that over‐representations of 2p14‐15, 6q23‐6q24, 15q22‐15q23, 22q11.2 and deletions of 1p36.1‐36.2, 4q31.3, 4q35, 8q12‐q21, 8p11.2 and 9p22 were significantly associated with shorter disease‐specific survival, whereas over‐expression of 20q13.3 and deletion of 18q11.2 were significantly associated with longer disease‐specific survival in this collection of colorectal cancers. Multivariate Cox proportional hazards regression models consistently identified gains of 2p14‐15, 15q22‐23, 22q11.2 and losses of 1p36.1‐36.2 and 4q35 as independent markers of shorter patient survival carrying greater significance than the classical clinicopathological parameters of nodal status and tumour grade.Conclusions: These five markers allow a molecular categorization of patients into high and low clinical risk groups. Thus, the genomic data have refined the histopathological classification highlighting the necessity for a supplementary genetically based stratification of colorectal cancer.
Cytokeratin‐positive interstitial cell neoplasm: a case report and classification issues
Authors: Schuerfeld K , Lazzi S , De Santi M M , Gozzetti A , Leoncini L , Pileri S A 
Published: December 2004

Aims:  Tumours of dendritic/accessory cell origin are rare neoplasms arising in lymph nodes. Among these, tumours derived from cytokeratin‐positive interstitial reticulum cells (CIRCs), a subset of fibroblastic reticulum cells, are reported even less frequently. The International Lymphoma Study Group (ILSG) has recently proposed a classification for tumours of histiocytes and accessory dendritic cells in which CIRC tumours are not included. We report a case of a CIRC tumour arising in a submandibular lymph node of a 66‐year‐old male.Methods and results:  The neoplasm was composed of spindle cells with elongated or round nuclei, prominent nucleoli and abundant cytoplasm. These cells were arranged in a diffuse fascicular and vaguely whorled pattern. The tumour cells stained diffusely for S100, vimentin, desmin, lysozyme, and focally for CD68 and cytokeratins 7, 8, 18, CK‐AE1 and CK‐pool. Electron microscopy was performed for further evaluation on samples taken from the paraffin block; this revealed cytoplasmic projections and rudimentary cell junctions.Conclusions:  Histopathologist should be aware of the existence of tumours deriving from CIRCs, as these cases may be misdiagnosed as metastatic carcinoma. Careful clinical and pathological evaluation is necessary to exclude this possibility.