bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal autonomic nerve tumors: Immunohistochemical and ultrastructural studies in cases of gastrointestinal stromal tumor
Authors: Matsumoto Koshi , Min Wen , Yamada Nobutaka , Asano Goro
Published: December 2008

The gastrolntestlnal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor with a morphological feature resembling the cell processes of the enteric plexus, and was originally teimed a plexoma or plexosarcoma. Light microscoplc studies show the GAN tumor most often consists of spindle‐shaped cells indistinguishable from a smooth muscle tumor or Schwann cell tumor. Immunohistochemical and ultrastructural examinations of 18 cases of gastrointestinal stromal tumor (GIST) were performed. During ultrastructural examination, all of the 12 cases which were immunohisto‐chemically positive for S‐100 protein or neuron‐specific eno‐lase (NSE) showed synapse‐like structures containing dense core neurosecretory granules measuring 100–200 nm, and 40–60 nm endocytoplasmic vesicles. These results suggest that most GIST of neurogenlc origln are tumors derived from the myenteric nerve plexus.
Origin of intraepithelial apoptotic cells in human colorectal adenomas
Authors: Arai Tomio , Maruyama Keiji , Kamo Takaharu , Sugimura Haruhlko
Published: December 2008

The origin of lntraepithellal apoptotic cells in human colorectal adenomas was examined using lmmunohistochemistry. Tissue sections of human colorectal adenomas obtained during surgery or endoscopy were stained by the streptavidin‐biotin method using antlbodies agalnst carcinoembryonlc antigen (CEA) and leukocyte common antigen (LCA). Approximately 15.7% of apoptotlc bodies stained postfive for CEA with Immunoreactivtly on the cytoplasm, whereas all cells stained negative for LCA. These findings suggest that Intraepithelial apoptosls in human colorectal adenomas origlnates from adenoma cells rather than infiltrating lymphocytes as previously proposed, and that apoptotic cells maintained their cytoplasmic antigenicity In the early stages of apoptosls.
Morphological characteristics of Epstein‐Barr virus‐related early gastric carcinoma: A case‐control study
Authors: Arikawa Junkou , Tokunaga Masayoshi , Satoh Elichi , Tanaka Sadao , Land Charles E.
Published: December 2008

A strong association between Epstein‐Barr virus (EBV) and gastric carcinoma has been demonstrated by the uniform presence of EBV In all carcinoma cells, episomal monocionallty, elevated antibodies, and a unique ‘lace pattern’ in the mucosa. The present study is concerned with morphological changes of Intramucosal carcinoma and submucosal Invasion. reactive lymphocytes, and with atrophy and Intestinal metaplasia of the surrounding mucosa. Fifty‐two EBV‐positive early gastric carcinomas were matched by age, sex, and site of tumor with 103 EBV‐negative carcinomas, all of which had previously been examined by serial cut‐sections of the tumors and surrounding mucosa. Epstein Barr virus Involvement was strongly associated with lace pattern morphology as demonstrated previously, and with lymphocytic Infiltration In and around the tumor nests In the mucosa. The Infiltrating lymphocytes In the tumor nests were mainly composed of CD8+ T lymphocytes. Lympho‐epithelioma (LE)‐like carcinoma, was observed in the sub mucosal portions of 13 of 31 EBV‐positive cases with such Invasions, Including 12 of 29 with lace pattern morphology in the mucosa. The majority of the surrounding gastric mucosa showed moderate to severe atrophy with marked depletion of parietal cells, complete‐type intestinal metaplasia in EBV‐positive cases, andHelicobacter pyiori (H. pyiori) Infection for both EBV positive and EBV‐negative cases. it is suggested that EBV infection may occur in the atrophic gastric epithelial cells associated with intestinal metaplasla andH. pyloriInfection, leading to the development of carcinoma. Such cancers show lace pattern and marked lymphocytic reaction in the mucosa, with some tendency for histological change and lymphocytic reaction during the invasive process without lymph node metastasis.
A human gall‐bladder signet ring cell carcinoma cell line
Authors: Nishida Tetsuro , Iwasaki Hiroshi , Johzaki Hiroshi , Tanaka Shinnosuke , Watanabe Ryoji , Kikuchi Masahiro
Published: December 2008

To date, very few reports of the establishment of gall‐bladder cancer cell lines have appeared,1–7 although many cancer cell lines of various kinds have been established. On the other hand, no reports could be found on signet ring cell carcinoma cell lines derived from the gall‐bladder and only five cell lines from the stomach. A human gall‐bladder cancer cell line (FU‐GBC‐2) was established In tissue culture from the ascitic fluid of a 69‐year‐old Japanese female patient. The tumor cells growing In tissue culture exhibited the morphological characteristics of signet ring cells In phase contrast and electron microscopy. The population doubling time was 43 hours. Heterotransplantation was succeeded by inoculation into me dermis of BALB/c nude mice. An Immunocytochemical study showed that most of the cultured cells were positive for carclnoembryonic antigen, CA19–9 and epithellal membrane antigen, but negative for vimentin. The modal chromosome number was 120 with a range of 100–124. Flow cytometry showed an aneuploidy pattern in the cultured cells at passage 30. Markedly amplified c‐myc oncogene was observed by Southern blot analysis. This cell line may be useful In the study of the morphological and biological characteristics of signet ring cell carcinoma and gallbladder adenocarcinoma.
Endometrial low‐grade stromal sarcoma with ovarian sex cord‐like differentiation: Report of two cases with an immunohistochemical and flow cytometric study
Authors: Fukunaga Masaham , Miyazawa Yoshio , Ushigome Shinichim
Published: December 2008

Two cases of endometrial low‐grade stmmal sarcoma with ovarian sex cord‐like differentiation occurring in a 39‐year‐old woman and a 42‐yearold woman are presented. Both tumors, which were intramyometrial and measured 7.5 cm and 7.0 cm in greateat diameter, respectively, showed a multinodular, ill‐demarcated, and yellowish white cut‐surface. Histologically, most parts of the tumors were composed of trabecular, cord‐like, or plexiform arrangements that were reminiscent of the growth pattern seen In ovarian sex cord tumors. Features of conventional endometrial low‐grade sttomat sarcoma were only focally observed. The tumors showed inflitrative margins and lymphatic invasion. The tumor cells were positive for vimentin, desmin, α‐smooth muscle actin, and muscle actin (HHF35).The tumors were also positive for both estrogen and progesterone receptors. Both tumors were DNA diploid as determined by flow cytometry. One patient had recurrences, Including oste olytic lesions in the pelvic bones, but had no evidence of recurrence or metastasis 11 months after the last surgery. The other patient had no evidence of tumor in a limited follow‐up. Famillarity with the neoplasm and other uterine mesenchymal tumors with ovarian sex cord‐like differentiation by gynecologists and pathologists is essential in avoiding misdiagnosis because adjuvant hormonal therapy may be effective in treating lowgrade stromal gammas.
Cyclin D1 over expression in malignant lymphomas
Authors: Nakamura Shigeo , Yatabe Yasushi , Seto Masao
Published: December 2008

Cyclin D1, the regulatory subunit of certain protein kinases thought to advance the G1 phase of the cell cycle, is now established as a protooncogene, with evidence indicating that its derangement may contribute to the uncontrolled cell growth characteristic of tumors. The chromosomal translocation t(11;14)(q13:q32), Involving rearrangement of the BCL‐1 locus, is closely associated wlth human lymphoid neoplasia affecting mantle cell lymphomas (MCL). Recently, the putative BCL‐1 protosncogene turned out to be none other than the cydin D1 gene. Although the observed break points In the BCL‐7 locus are not tightly clustered, Its rearrangement has been documented In 40–70% of cases of mantle cell lymphoma, whereas it only rarely occurs in other B cell lymphomas. Of note, all of the known break points leave the cyclin D1 coding region structurally Intact and result In increased protein expression, implying that this may provide a highly sensitive and specific marker for MCL. Recent studies demonstrated that immunohistochemical detection In paraffin‐embedded material, using a mone clonal antibody, Is very useful for routine diagnosis. Current knowledge of cydin D1 over expression In malignant lymphomas, with emphasis on its clinic pathologic significance, is reviewed.
Suppressive effects of Sairei‐to on monoclonal antibody 1–22–3‐induced glomerulonephritis: Analysis of effective components
Authors: Ii Ping , Kawachi Hiroshi , Morioka Tetsuo , Orikasa Mlchiaki , Oite Takashi , Shi Zhen Sheng , Shimizu Fujio
Published: December 2008

The effects of treditional Chinese medlclne (Salrel‐to) on experimental glomerulonephritls Induced In rats by monodonal antibody (mAb) 1–22–3 lnjectlon was examined. The level of proteinuria in the Sairel‐to‐treated group was significantly lower than that In the PBS treated group. This suppressive effect was caused by the major component of Sealer‐to, Syo‐salko‐to but not by another component, Gorel‐san. The suppressive effect of Syo‐salko‐to was Identified In Its components (Bupleuri radix, Pindilae tuber and Zingibers rhizoma), but not In the other combined components (Ginseng radix and Zizyphl fructus). Further study weeled that the suppressive effects of the combined components were mainly derived from Bupleuri radix. It was demonstrated that the actual active Ingredient is probably Salkosaponin‐d. Light microscopy revealed that Sairel‐to and Its effective components suppressed the proliferation of mesanglal cells and mesanglal matrix expansion. Semi quantitative morphological studies of glomerular lesions on the eighth day showed that Syo‐salko‐to and Its combined components (Bupleuri radix, Zinglberis rhizoma and Pinelliae tuber) suppressed mesanglal matrix expansion significantly compared with phosphate‐buffered saline control groups (matrix score: 28.0±19.1 vs 102.3±14.1; 30.9±30.1 vs 102.3±14.1, p<0.005, respectively). It was concluded that Salkosaponln‐d, as well as Bupleuri radix, Syo‐salko‐to and Sairel‐to can suppress proteinurla and morphological changes In the rat glomerulonephritls model Induced by mAb 1–22–3.
Malignant lymphoma induction of rabbits with oral spray of Epstein‐Barr virus‐related herpesvirus from Si‐IIA cells (HTLV‐II‐transformed Cynomolgus cell line): A possible animal model for Epstein‐Barr virus infection and subsequent virus‐related tumors in humans
Authors: Koirala Tirtha Raj , Hayashi Kazuhiko , Chen Hong‐Li , Ino Hideo , Kariya Naoyuki , Yanai Hiroyuki , Choudhury Chitta Ranjan , Akagi Tadaatsu
Published: December 2008

Malignant lymphoma (ML) was Induced in eight of nine rabbb inoculated by oral spray of the cell‐free pellets from SI‐IIA culture (MLV‐ll‐transformed leukocyte cell line of the Cynomolgus‐producing Epsteln‐Barr virus (EBV)‐related herpesvirus) after 64–141 days. None of the rabbits inoculated with EBV from B‐95–8 cells or HTLV‐II from MOT cells developed ML. Malignant lymphomas were usually of diffuse, large‐cell or mixed type. HTLV‐II infection was excluded by the polymerase chain reaction (PCR) and the particle agglutination test. EBV‐encoded RNA‐1 and EBV‐related DNA were detected in the tumor tissues by In situ hybridization and PCR, respectively. Anti‐viral capsid antigen of EBV antibody (anti‐VCA) was observed 3 weeks after oral inoculation of Si‐IIA cell‐free pellets. Polymerase chain reaction revealed continuous detection of EBV‐related virus DNA in the peripheral blood leukocytes from 3 days after oral inoculation. These results show that ML induced orally wtth SI‐IIA cell‐free pellets was caused by EBV‐related herpesvirus harbored by Si‐IIA cells. Oral spray of EBV from B‐95–8 also induced EBV Infection in rabbits, which was confirmed both by the presence of anti‐VCA and by PCR. These oral infection and mallgnant lymphoma induction systems of rabbit using EBV‐related virus from Si‐IIA or human EBV are useful animal models for the study of EBV infection and EBV‐related lymphomas in humans.
Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung
Authors: Kodate Mantaro , Kasai Takahiko , Hashirnoto Hiroshi , Yasumoto Kosei , Iwata Yasushi , Manabe Hideo
Published: December 2008

The expression of matrix mdalloproteinase‐2 (MMP‐2; 72 kDa type IV collagenase/gelatinase A) and MMP‐9 (92 kDa type IV collagenase/gelatinase B) was Immunohisto chemically Investigated In 79 T1 adenocarcinomas of the lung using non‐commerclal polydonal anti‐MMP‐2 and ‐9 antibodies. Thirty‐two (41%) and 22 (28%) among the 79 cases were positive in the tumor cells for MMP‐2 and ‐9, respectively. The incidences of MMP‐2 and ‐9 Immunoreactivities were higher (64 and 45%, respectively) in poorly differentiated tumors than in well differentiated tumors (36 and 25%, respectively), and lower in bronchloloalveolar carcinoma (22 and 10%, respectively) compared with other subtypes of adenocarcinoma. The prognosis for patients with MMP‐2 andor ‐9 positive Immunoreactivities was significantly poorer than for those with a MMP‐negative tumor (P<0.05). The degree of collagenization was divided into four grades, and tumors with a small to abundant amount of collagen (grade 2 and grade 3 fibrosis) had a higher Incidence of Immunoreactivity to both types of MMP. It is estimated that these expressions might be responsible for tumor Invasion, metastasis, and for grade 2 and grade 3 fibrosis In T1 adenocarcinoma of the lung.
Adrenal rest tumor of the broad ligament: Case report with immunohistochemical study of steroidogenic enzymes
Authors: Sasano Hironobu , Sato Shinji , Yajima Akira , Akarna Jirou , Nagura Hiroshi
Published: December 2008

An adrenal rest tumor of the broad ligament was studled In a 43‐year‐old woman. The tumor measuring 6×3×3 cm and appearing as golden‐yellow on the cut surface was lncidentally discovered during a total hysterectomy due to uterine leiomyoma. The encapsulated tumor was predominantly composed of pale and lipid‐rich cells arranged in alveolar clusters or short blunt cords. Electron microscopic examination revealed mitochondria with tubule‐veslcular cristae and abundant lipid droplets. Adrenal 4‐binding proteln, a transcriptional factor of steroidogenesis, was present in almost all of the tumor cells, suggestive of steroldogenic features in the lesion. lmmunoreactivity of steroidogenic enzymes involved In adrenocortical steroid production was detected in the tumor cells, suggesting that tumor cells had the potential to synthesize adrenocortical steroids. A relativety low KI‐67 labeling index (3.20±1.15 per 100 tumor cells) and an absence of necrosis and vascular andlor capsular invasion suggest benlgnity of the leslon.
Correlation of p53 protein expression with gene mutation in gall‐bladder carcinomas
Authors: Itoi Takao , Watanabe Hidenobu , Yoshida Mitsuhiro , Ajioka Youichi , Nishikura Ken , Saitd Toshihiko
Published: December 2008

The correlation of p53 protein expression and p53 mutation of 33 gall‐bladder carclnomas was studied accordlng to the depth of invasion and grade of cytological atypia. Overexpresslon of p53 protein was detected by immunostaining in seven (70.00/) of 10 intramucosal and in 16 (69.6%) of 23 invasive carcinomas. p53 mutation was detected in five (71.4%) of the seven intramucosal carcinomas with overexpresslon and In eight (50.0%) of the 16 invasive cancers with overexpression and in one (10%) of the 10 non‐overexpressing carclnomas at exons 5–8 by nested polymerase chain reactlon‐single‐strand conformatlon polymorphism. The overexpression of p53 protein was present In nine (56.3%) of 16 low‐grade carcinomas and In 14 (82.3%) of 17 high‐grade carcinomas. In cases of overexpresslon, p53 mutatlon was detectable in four (44.4%) of nlne lowgrade and in nlne (64.3%) of 14 high‐grade carclnomas. In total, p53 mutation was verified In 56.5%0 (13123) of cases involving protein overexpression and in 10% (1/10) of cases of nonoverexpresslon. The sensltivity of p53 mutation was 56.5% (13/23), the specificity was 90.0% (9/10) and the validity was 1.47. in conclusion, our study indicates that p53 protein overexpression correlates well wlth gene mutatlon and that p53 alteration may be related to increaslng grade of cytologic atypla of carclnomas.
Immunohistochemical localization of endothelin‐1, endothelin‐3 and endothelin receptors in human pheochromocytoma and paraganglioma
Authors: Watanabe Kazuo , Hiraki Hiroyukl , Hasegawa Hiroshi , Tanigawa Toshitaka , Ernura Iwao , Honma Kei‐ichi , Shibuya Hiroyuki , Fukuda Takeaki , Suzuki Toshimitsu
Published: December 2008

Endothelln (ET) and its receptor system have been shown to exert varlous biological effects on dlfferent types of cells In addition to their well‐known vasoconstrictor activity. Recently ET‐1, ET‐3 and the ET3 receptor have been shown to play an Important role In the development of neural crest‐derived cells and, in this context, pheochromocytomas have been reported to harbor ET‐1. Endothelin‐3 or ET receptor subtypes, however, have not been examined in pheochromocytoma and paraganglioma so far. In the present study the Immunohistochemical localization of ET‐1/big ET‐1, ET‐3/big ET‐3 and the ETA and ETB receptors were lnvestigated to clarify the biological characteristics of these two tumors using 32 pheochromocytomas and 11 extra‐adrenal paragangliomas. Endothelin‐lhig ET‐1 was detected in 19 pheochromocytomas (59%) and eight paragangliomas (72%), while ET‐3hIg ET‐3 was detected in 10 pheochromocytomas (31%) and three paragangllomas (27%). The ETA receptor was found in 21 pheochromocytomas (66%) and In eight paragangllomas (73%), whlle the ETB receptor was found in 25 pheochromocytomas (78%) and In eight paragangllomas (73%). Normal adrenomedullary cells lacked each antigen examined. Endothelin‐immunoreactive tumor cells were dlstrlbuted focally or In a manner scattered, whlle receptor‐immunostained tumor cells were distributed wlth a focal pattern for the ETa receptor and wlth a focal or diffuse pattern for the ETB receptor. Endothelln and its receptor coexlsted In the same tumor in 21 of 28 ET‐posltive pheochromocytomas and in eight of 10 ET‐positlve paragangliomas. In additlon, seven pheochromocytomas and two paragangllomas revealed posltivlty of the receptor(s) irrespective of the absence of ET‐immunoreactlvlty. In concluslon, ET and Its receptor are frequently and concomitantly expressed in the pheochromocytoma and paraganglloma. From the highly frequent expression of this system or the receptor(s), ET‐receptor‐mediated slgnal transduction of these tumors concernlng growth and/or cell survival Is expected, although definite blological slgniflcance of thls llgand‐receptor system in these tumors awaits further Investigation.
Analysis of hyperplastic foci in livers with hepatocellular carcinomas by flow cytometry and AgNOR staining
Authors: Ikebe Takashi , Wakasa Kenlchi , Shuto Taichi , Okuda Toyokazu , Yamamoto Takatsugu , Hirohashi Kazuhiro , Kinoshita Hiroaki , Sakurai Masami
Published: December 2008

The phase S ratlo in cell cycles were analyzed in livers with hyperplastic foci (HPF) and in livers without HPF by nuclear DNA determinatlons using flow cytometry, and by stalning wlth argyrophilic protelns of the nucieolar organlzer reglon (AgNOR). Flow cytometric analysis was done on 50 fresh frozen speclmens of livers resected from 50 patients wlth hepatocellular carcinoma (HCC). Paraffin sections from the same patients were analyzed uslng AgNOR staining. There were 25 cases each wlth and without HPF. We examined the stage of fibrosis and the grade of inflammatory activity according to the modlfied Scheuer and Desmet scale. The incidence of HCC recurrence among these patlents was also studied. The average phase S ratio of the livers of the patients with HPF was 6.5+3.2%, and that of the livers of the patients without HPF was 4.0±2.5%. The ratio differed slgnificantly between the two groups (P<0.01). The average AgNOR score for HPF lesions of the HPF‐positlve cases was 1.6020.34, that for non‐HPF lesions In the HPF‐positive cases was 1.2920.12, and that for the HPF‐negative cases was 1.1920.14. Significant differences were found between the average AgNOR scores for HPF lesions of the HPF‐posltive cases and the non‐HPF lesions of the HPF‐posltive cases (P<0.0l), as well as between the non‐HPF lesions in the HPF‐positive cases and the HPF‐negatlve cases (P‐cO.05). Severe fibrosis (stage 3) and cirrhosls (stage 4) were found In 76% of HPF‐positive cases and 48% of HPF‐negatlve cases. The llvers of HPF‐posltlve patlents were slgnificantiy more cirrhotic than those of HPF‐negative patients (R0.05). The association between HPF and the Inflammatory grade was not slgnlficant (Ao.05). The incldence of HCC recurrence among HPF‐positive cases was significantly higher than that among the HPF‐negative cases (P<0.05). The average phase S ratio of the recurrent HPF‐positive patients was 7.48+3.48%, slgnlficantly higher than that of HPF negative cases (5.57*3.06%, Pc0.05). Hyperplastic foci of the llver was shown to be a hlghly prollferatlve lesion. The proliferative activity of the non‐HPF lesions in the HPF‐positive patients was also higher than that of the HPF‐negative patients. Hyperplastic focl tended to be present in cirrhotic livers, but it was not associated wlth the grade of inflammatory activlty of the Iiver. Hyperplastic focl may represent an important predictor of recurrence after hepatic resection.
Gastric carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation
Authors: Nakayama Yoshifuku , Murayama Hiroshi , Iwasaki Hiroshi , Iwanaga Shin‐ichi , Kikuchi Masahiro , Ikeda Seiyo , Okada Mitsuo , Iizuka Yoshihiko , Iwashita Akinori
Published: December 2008

A rare case of carclnosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentlatlon occurrlng in the gastric remnant is reported. A 69‐year‐old Japanese man who had undergone a partial gastrectomy for a duodenal ulcer 30 years earlier, presented with anemla, eplgastralgia, and an abdominal mass. The diagnosls of gastric carcinosarcoma was made based on the findings of endoscoplc biopsies. The patient was thus scheduled to undergo a surgical operatlon, but he died of respiratory failure. At autopsy, a huge polypoid tumor measurlng 2Ox18times8 cm was located on the greater curvature of the gastric remnant. Microscopically, the tumor conslsted of Intimately mixed tubular adenocarcinoma and heterologous mesenchymal elements contalning rhabdomyosarcoma and osteosarcoma. Between these components, a morphological transition from the adenocarclnoma element to the sarcomatous element was observed. Ultrastructually, rhabdomyoblastlc dlfferentlation was conflrmed In the sarcomatous areas. lmmunocytochemlcal expresslons of epithelial markers includlng epithelial membrane antlgen and cytokeratlns (35bHll and 34bE12) were recognlzed not only in the carclnomatous cells but also In the sarcomatous cells. These findlngs suggest that carclnomatous cells appear to transform Into cells wlth sarcomatous features.
Ameloblastic fibrosarcoma arising de now in the maxilla
Authors: Tajima Yoshifumi , Utsumi Nobuo , Suzuki Seiji , Fujita Kuniya , Takahashi Hiroshi
Published: December 2008

An ameloblastlc fibrosarcoma (AFS) arlsing in the maxilla of a 14‐yearold male Is descrlbed. The tumor orlglnated from the alveolar bone of the right maxllia with no apparent history of pre‐exlstlng leslon. Histologically, the lesion was composed of benign‐appearlng epithelial Islands and strands scattered within an exceedingly cellular mass of mesenchymet tissue comprislng 8 large number of steliate‐and spindle‐shaped fibroblast‐like cells with marked pleomorphlsm. Occasional cementum‐like calcification was also noted. Immunohistochemically, the neoplastlc mesenchymal cells were positive only for vimentln, whereas the ameioblast‐like epithelial component showed a dlstlnctly positive reactlon for wide‐spectrum keratin and squamous cytokeratin. Clinicopathological features of the current case, as well as previously reported examples of AFS originating from the maxilla, are briefly discussed.
Melanocytes in the human parotid gland
Authors: Takeda Vasunori
Published: December 2008

A review of the literature yields about 20 reported cases of purportedly primary malignant melanoma of the parotid gland, but no convincing examples of pre‐existent melanocytes in the salivary glands. The present paper reports the existence of melanocytes In the interlobular duct of the parotid gland observed during an autopsy case of a Japanese male. Melanocytes with long cytoplasmic processes were distributed in the basal and suprabasal layers of hyperplastic duct epithelium, and melanin granules were sparsely scattered in the duct epithelial cells. This is the first report of melanocytes in the human salivary gland.
Testicular seminoma with human chorionic gonadotropin production
Authors: Hori Kazutoshi , Uematsu Kunio , Yasoshima Hitoshi , Yamada Aklhiko , Sakurai Kazunari , Ohya Munehiko
Published: December 2008

Testicular seminoma with elevated serum human chorionic gonadotropin level (hCG‐positive seminoma) is regarded as more malignant than marker‐negative seminoma, although Its prognosis is still unclear. To clarify the malignant potential of seminoma with hCG production, the serum levels of the beta subunit of hCG (β‐hCG) and lactic acid dehydrogenase (LDH) were examined in 35 and 40 patients, respectively, and the Immunohistochemical expression of β‐hCG examined in 45 tumors. The elevation of the LDH serum level correlated to the Invasive status, metestatic status and poor outcome, while that of the serum β‐hCG level correlated only to the metastatic status. Immunohistochemical expression of β‐hCG was observed in syncytiotrophoblastic giant cells in 11 tumors and a few mononuclear seminoma cells In 36 tumors. Expression was not associated with the malignancy potential, except where the expression In mononuclear cells Inversely correlated to the invasive status. These results suggest that most seminomas produce a slight amount of hCG; that an elevated hCG serum level Indicates the pressnce of metastatic tumors and mainly reflects an increase in tumor volume but not in cellular malignancy potential; and that the LDH serum level, rather than hCG, is more useful as a prognostic indicator for patients with seminoma.
High reactivity of monoclonal antibody (TO73) with human malignant tumor cell line
Authors: Kakihara Toshio , Fukuda Takeaki , Yamada Toshiyuki , Tanaka Atsushi , Uchiyama Makoto , Naito Makoto , Emura Iwao
Published: December 2008

The biological characteristics d a new monoclonal antibody (TO73) reacting with a vincristine‐resistant human leukemic cell line (KY‐VCR) were, evaluated. Immunological and electron‐immunological studies showed that TO73 reacted with the surface glycoprotein of KY‐VCR. TO73 was found to have no effect on cell growth and intracellular uptake of vincristine. In human neoplastic cell ilnes TO73 was found to react with 11 of 27 (41%) cell lines. With regard to de novo primary tumor with one exception, TO73 did not react with any of the examined primary tumor cells. The patient with TO73‐positive leukemia died of induction failure due to drug resistance. Complete remission was achieved in the other leukemic patients. These results indicate that TO73 antigen may be associated with immortalization of tumor cells and poor prognosis in some cases.
Primary squamous metaplasia of the breast
Authors: Mills Alan E. , Daniel William J.
Published: December 2008

A case of primary or idiopathic squamous metapiasia of the breast occurring in a 45‐year‐old woman is presented. Immunohistochemical studies suggested that the metapiasia had arisen in ductular eplthellum. No evidence of neopiasia was identiffied.
Immunohistochemical study on histogenesis of congenital epulis and review of the literature
Authors: Uǧraš Serdar , Demírtaš Ísmall , Bekerecioǧlu Mehmet , Kutluhan Ahmet , Karakök Metin , Peker Öder
Published: December 2008

Congenital epulis is a very rare lesion found only in newborn infants. This tumor is multiple in about 10% of reported cases, rarely with the simultaneous involvement of the maxilla and mandibula, as in this article. In the presented case, light microscopy demonstrated large eosinophilic granular cells arranged in solid nests that are separated by thin fibrovascular areas. The tumors In the maxilla and mandibula were investigated with a panel of polyclonal and monoclonal antibodies, and using immunoperoxidase methods on formalin‐fixed, paraffin‐embedded sections. Immunohistochemical studies revealed strong and diffuse cytoplasmic staining for neuron specific enolase and vimentin. However, all other reactions were negative. These results suggest that the congenital epulis may be derived from uncommitted nerve‐related mesenchymal cells.
Dedifferentiated liposarcoma with an inflammatory malignant fibrous histiocytoma‐like component presenting a leukemoid reaction
Authors: Hisaoka Masanori , Tsuji Seiji , Hashimoto Hiroshi , Aoki Takatoshi , Uriu Kohei
Published: December 2008

A rare case of dedifferentiated llposarcoma (well‐differentiated llposarcoma with an inflammatory mallgnant fibrous histiocytoma (MFH)‐like anaplastlc component) occurrtng in a 69‐year‐old male is presented. The patient had noticed a dull pain in his left loin and thigh for about 1 month. Computed tomography examination revealed a low‐density mass lesion, measuring about 6 cm In diameter, in the left lliopsoas muscie, and It was surgically removed. Grossly, the lesion was composed of an encapsulated, soft, whitish mass and an adjacent, well‐demarcated, yellowish hard nodule, measuring about 2.5 cm In diameter. Microscopically, both lesions showed features of an inflammatory variant of MFH and a sclerosing type of well‐differentiated liposarcoma, respectively. To our knowledge, only two cases of dedifferentiated liposarcoma combined with inflammatory MFH as a dedifferentiated component have been recorded in the literature. The salient feature of the present case is a systemic inflammatory reaction, as shown by prominent leukocytosis (up to 73 900/mm3) and the elevated serum value of C reactive protein (up to 26.0 mg/dL), which were transiently reduced after surgery. The Inflammatory reaction was suggested to be induced by cytokines, such as granulocyte colony‐stimulating factor and interleukin‐6, which were probably produced by the tumor cells in the present case, because the elevated serum values of those cytokines were decreased after surgery.
Angiomyofibroblastoma of the vulva: Case report with immunohistochemical, ultrastructural and DNA ploidy studies and a review of the literature
Authors: Sasano Hlronobu , Date Fumiko , Yamamoto Hironao , Nagura Hiroshi
Published: December 2008

A case of anglomyofibroblastoma of the vulva in a 49‐year‐old woman was examined. The tumor measured 3×2.5×2 cm and appeared light gray to tan In color on the cut surface. Light microscopic examinations revealed that spindle or oval shaped tumor cells were arranged in loose edematous stroma with numerous thin‐walled vessels. Ultrastructurally, cell organellae were not well developed but intracytoplasmic filaments of intermediate size were abundant in the tumor cells. Desmin, CD34 and vimentin immunoreactivity were detected in almost all of the tumor cells. Both estrogen and progesterone receptors were diffusely expressed In the tumor, suggestive of the sex sterold‐dependency of this tumor. The Ki‐67 labeling index was less than 1% and the DNA content of the tumor cells, which was examined by image cytometry, demonstrated diploidy (DNA index=0.97). These findings may reflect the quiescent or slow growing features of angiomyofibroblastoma.
Costimulatory molecules (CD80 and CD86) on Reed‐Sternberg cells are associated with the proliferation of background T cells in Hodgkin's disease
Authors: Nozawa Yoshihiro , Wakasa Haruki , Abe Masafumi
Published: December 2008

To elucidate the relationship between Reed‐Sternberg (R‐S) cells and background T cells, the expression of CD80 and CD86 of R‐S cells in Hodgkin's disease (HD), and the ligand CD28 expression and the MIB‐1 index of background T cells were immunohistochemically investigated. CD80 and CD86 were found to be expressed on R‐S cells in almost all cases of HD. CD28 was expressed with strong intensity on many background T cells around R‐S cells. The MIB‐1 index of background T cells was 30.3% (range, 15.5–38.9%) and was much higher than 10.9% (range, 9.8–11.7%) in B cell lymphomas. These results suggest that the interaction between CD80 and CD86 on R‐S cells, and CD28 on background T cells may induce T cell proliferation and be associated with tumor mass of HD.
p53 protein expression in non‐Hodgkin's lymphomas is infrequently related to p53 gene mutations
Authors: Oka Takashi , Sarker Ashit Baran , Teramoto Norihiro , Yoshino Tadashi , Akagi Tadaatsu
Published: December 2008

Accumulation of the p53 protein has been found In several types of lymphomas. However, p53 gene mutations have been infrequently demonstrated in some specific types of lymphomas. In the present study, a correlation between p53 immunoreactivity and p53 gene mutations in a large panel of non‐Hodgkin's lymphoma (NHL) cases is attempted. A panel of 202 cases of NHL was evaluated by immuno‐hlstochemical staining for p53 protein. All cases that were immunohistochemically positive for p53 protein were analyzed by the polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) method to identify mutations within the pS3 gene. In order to confirm the mutation, sequencing of PCR‐amplified p53 gene segments was performed. Overexpression of p53 protein was found in 59 of the 202 cases of NHL, but only four of these 59 cases showed a shift on SSCP analysis, and point mutations were detected in three of them by the subsequent sequencing. p53 Immunoreactivity was generally greater in high‐grade lymphoma. The results of this study suggest that Immunohistochemlcal reactivity for p53 protein is not a reliable Indicator of the presence of their structural alterations of p53 gene exons 4–9 in NHL.
Upregulation of nucleobindin expression in human‐activated lymphocytes and non‐Hodgkin's lymphoma
Authors: Kubota Tetsuo , Mlyauchl Motohiro , Miura Keljl , Hirokawa Goh , Awaya Akira , Miyasaka Nobuyuki , Kurosawa Yoshikazu , Kanal Yoshiyukl , Maruyama Koshi
Published: December 2008

Nucleobindin (Nuc) was originally found to be an enhancement factor of antl‐DNA antibody production secreted by a lymphold cell line derived from a lymphoprollferatlve MRL/Ipr mouse. It has been shown that Nuc has a unique structure containing a DNA‐ and two calcium‐binding domains, and a leuclne zipper motif, but Its biological roles have not yet been fully elucidated. Expression of Nuc was first studied in human lymphocytes. Expression of Nuc mRNA in normal peripheral blood mononuclear cells was significantly increased upon mitogen stimulation. Anti‐human Nuc monoclonal antibody H‐1D8 immunopreclpitated Nuc protein in the nuclear extract of Molt‐4 cells. Furthermore, in the immunohlstochemlcaf staining of tumor specimens from 108 patients with non‐Hodgkin's lymphoma (NHL) with H‐1D8, H‐1D8‐posltlve cells were observed in nearly all cases in varying frequency. According to the Working Formulation, the percentage of cases in which more than 90% of the tumor cells were stained with H‐1D8 was 65% in the high grade of the histological malignancy, 54% In the Intermediate grade, and 22% in the low grade; however, normal ceils surrounding the tumor cells were virtually negative for H‐1D8. These results showed that the level of Nuc expression in human lymphocytes reflects the status of activation or proliferation of the cells, thus providing a clue for the further investigation into biological roles of Nuc. In addition, It might be applicable to the clinlcopathological estimation of NHL as a novel Indicator.
Prognostic significance of Ki‐67, p53, and Bcl‐2 expression in prostate cancer patients with lymph node metastases: A retrospective immunohistochemical analysis
Authors: Masuda Mitsunobu , Takano Yasuo , Iki Masayuki , Asakura Tomoyuki , Hashiba Takafumi , Noguchi Sumio , Hosaka Masahiko
Published: December 2008

The prognostic significance of Ki‐67, p53, and Bcl‐2 expression was evaluated in prostate cancer patients with lymph node metastases. Immunohistochemical staining of archived material obtained from 56 patients was performed by the streptavldin‐biotin method. Univariate survival analysis showed that a Ki‐67 labeling index (Ki‐67 LI) of ≥8.4 in the primary tumor identified a group of patients with a significantly poorer prognosis (P<0.001). Furthermore, a Ki‐67 LI of ≥8.7 in the nodal metastatlc tumor was also associated with a poorer prognosis (P<0.01). Multivariate analysis showed that the Ki‐67 LI of primary tumors (P<0.01) and lymph node metastases (P<0.01) had independent prognostic value. p53 and Bcl‐2 expression had no prognostic value in patients with prostate cancer and lymph node involvement. The Ki‐67 LI has more prognostic value than p53 and Bcl‐2 expression for patients with prostate cancer that has spread to the lymph nodes.
The first reported case of intestinal spirochaetosis in Japan
Authors: Nakamura Shin‐lchl , Kuroda Tuguhisa , Sugai Tamotsu , Ono Sadahide , Yoshida Toru , Akasaka Iichiro , Nakashima Fumie , Sasou Shunichl
Published: December 2008

A 65‐year‐old Japanese male consulted Ozuchi Prefectural Hospital (Iwate, Japan) on 19 January 1994 complaining of weight loss. Cecal mucosal biopsy material, which was stained with hematoxylln‐eosin revealed a thick, basophllic fuzzy fringe covering the surface epithelium. Transmission and scanning electron microscopy observations demonstrated the presence of slightly wavy spirochaetes with tapered ends, which were attached to the surface epithelium of the colonlc mucosa via one of these ends. The patient did not display any clinical symptoms of Inflammatory bowel disease, and laboratory tests eliminated an Immunodeficiency condition. Thus, in the present case, the Intestinal spirochaetes appear to be harmless commensals. This paper presents the first reported case of Intestinal spirochaetosis fn Japan.
Metastatizing low‐grade clear cell leiomyosarcoma of the uterus
Authors: Karpuz Vildan , Joris François , Letovanec Nicolas , Branchmanskl Franchise , Kapanci Yusuf
Published: December 2008

An unusual case of uterine clear cell tumor is reported In a 56‐year‐old woman. The neoplasm was Identified as a peculiar low‐grade leiomyosarcoma, composed mainly of watery, clear large cells with round, fairly regular nuclei. No appreciable pleomorphlsm or high mitotlc activity was noted. There was no necrosis. The presence of occasional areas of transition between these cells and typical spindle leiomyosarcoma cells, together with the immunohisto‐chemical results, allowed the recognition of a smooth muscle origin of this clear cell tumor. The patient was treated by hysterectomy. Six years later she developed an Inguinal metastasis resembling an hibernoma, and then later developed a large retroperitoneal metastasis, which was composed entirely of clear cells and was distinguished from a Ilposarcoma by Immunohlstochemlstry.
Coexpression of HGF and c‐Met/HGF receptor in human bone and soft tissue tumors
Authors: Fukuda Toshio , Ichimura Eiji , Shinozaki Tetsuya , Sano Takaaki , Kashiwabara Kenji , Oyama Tetsunari , Nakajima Takashi , Nakamura Toshikazu
Published: December 2008

To understand the interaction between hepatocyte growth factor (HGF) and its receptor c‐Met on various bone and soft tissue tumors, their expressions were investigated by western blot analysts, immunohistochemistry and enzyme immunoassay. Western blot analysis revealed that c‐Met protein was expressed in 21 (38.8%) of 54 tumors, which detailed to seven (25.9%) of 27 bone tumors and 14 (51.8%) of 27 soft tissue tumors. Most malignant fibrous histiocy‐tomas (MFH) and all neurofibromas expressed c‐Met protein. The highest expression of c‐Met protein was seen in a case of biphasic synovial sarcoma, where its immunoreac‐tivity was localized only on the epithelial component and not on the sarcomatous component. By enzyme immunoassay for HGF, all but one MFH showed HGF production and the mean level of HGF was the highest among the tumors investigated. Neurofibmmas and osteosarcomas had the next highest mean levels of HGF production, respectively. Coexpression of HGF and c‐Met was obsewed in 19 (35.2%) of 54 tumors and was frequently observed in neurofibroma, followed by MFH and synovial sarcoma. Although the mode of interaction between HGF and c‐Met varies among the various bone and soft tissue tumors including MFH, their signaling system may play an Important role in the development and progression of bone and soft tissue tumors.
c‐Met expression of thyroid tissue with special reference to papillary carcinoma
Authors: Oyama Tetsunari , Ichimura Elji , Sano Takaaki , Kashiwabara Kenji , Fukuda Toshio , Nakajima Takashi
Published: December 2008

It has become clear that papillary carclnomas of the thyroid often express the receptor for c‐Met/hepatocyte growth factor (HGF) receptor, but little Is known about the role of the HGF and c‐Met system In the pathogenesis of thyroid carcinoma. In this study, the expression of c‐MeUHGF receptor was evaluated in thyroid tlssue by western blot and immunohistochemistry, and compared with the concentration of HGF. Clinicopathologlcal characteristics were also compared. Fmeen of 20 papillary Carcinomas (75%) showed eMet bands of 145 kDa. No or only a low frequency of c‐Met expression was detected in healthy thyroid tissue (0/5), thyroiditis or Basedow's disease (0/2), adenomatous goiters (0/8), follicular adenomas (119, 11%) and undifferentiated carcinomas (0/2). These results were confirmed by immunohistochemistry, but a relatively higher frequency of c‐Met expression was detected in adenomatous goiters (25%), follicular adenoma (44%) ancl papillary Carcinoma (100%) using formalin‐fixed and paraffin‐embedded materials. A strong immunoreaction for c‐Met was observed In the tumor cytoplasm of paplllary carcinomas among the fibrous tissues situated at the perlphery of the tumor. The densito‐metrically measured expression of c‐Met had no relation to tumor stage in papillary carcinoma, but did correlate to the concentration of HGF in papillary carcinomas. In conclusion, in thyroid lesions, c‐Met was highly expressed specifically in the cytoplasm of papillary carcinomas. c‐Met expression was not related to the aggressiveness of the tumor but was related to the concentration of HGF, which was probably derived from the stroma. Also, the c‐Met system might play a role in the pathogenesis of papillary carcinoma of the thyroid.
Coexpression of hepatocyte growth factor andc‐Metproto‐oncogene product in synovial sarcoma
Authors: Motoi Toru , Ishida Tsuyoshi , Kuroda Masahiko , Horiuchi Hajime , Oka Teruaki , Matsumoto Kunio , Nakamura Toshikazu , Machinami Rikuo
Published: December 2008

Hepatocyte growth factor (HGF) is a heterodlmeric polypep‐tide growth factor that has pleiotropic roles, Including those of mitogen, motogen and morphogen. The HGF receptor Is characterized as ac‐Metproto‐oncogene product (c‐Met), which is a heterodimeric tyrosine kinase receptor. Hepatocyte growth factor acts as a mediator between the mes‐enchymal and epithelial tissues because HGF is produced by mesenchymal cells and c‐Met is mainly expressed on various epithelial cells. Furthermore, the HGF/c‐Met system plays an important role in embryogenesis and the regeneration of various organs. Synovial sarcoma (SS) are unique sarcoma that show epithelial differentiation, but little is known about their histogenesis. The expression of HGF and c‐Met was examined by immunohlstochemlstry In SS specimens from 12 patients (six each of biphasic and monopha‐sic fibrous types). lmmunohistochemical coexpression of HGF and c‐Met was demonstrated in the epithelial component of five biphasic SS, while only c‐Met was expressed in the epithelioid nests of three monophasic fibrous SS. The spindle cell component was negative for HGF and c‐Met. In SS, positivity for epithelial markers, such as cytokeratins and epithelial membrane antigen, was diffusely observed in the epithelial component and was focally observed In spindle cells, while vlmentin was positive predominantly in the spindle cell component. The areas expressing HGF and c‐Met corresponded to distinct epithelial structures; however, HGF and c‐Met expression were not found in any other tumor cells expressing epithelial markers in the spindle cell component of SS. Considering the morphogenlc effect of HGF, which has been known to be one of Its most important roles, the unique immunohlstochemical localization of HGF and c‐Met In SS suggests that the HGF/c‐Met system may be closely related to the formatlon of epithellal (glandular) structures In biphasic SS.
nm23‐H1 protein immunoreactivity in intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix
Authors: Lee C. Soon , Gad Jacqueline
Published: December 2008

Differences In the Immunohlstochemlcal expression of the 17 kDa protein encoded by the human nm23‐H1 gene were studied In premallgnant lesions and Invasive squamous cell carcinoma (SCC) (N = 8) of the cervix using routine streptavldln‐blotln Immunohistochemlstry and a polyclonal antibody to the nm23‐H1 protein. The premalignant lesions were kollocytic atypla due to wart virus Infection (N = 5), low‐grade cervical intraepithelial neoplasia (CIN) (N = 7) and high‐grade CIN (N = 7). The carcinomas were either moderately (N = 3) or poorly differentiated (N = 5). The non‐neoplastlc controls were normal squamous epithelium from cases with uterine prolapse (N = 7) and normal squamous epithelium not affected by the Infective or neoplastic areas of some of the cases with wart virus Infection (N = 2) and carcinoma (N = 2). Moderate to strong cytoplasmic and, occasionally, nuclear Immunostainlng for the nm23‐H1 protein was seen in all cells above the basal layer of the normal squamous epithelium. However, most of the cervical SCC show a relative reduction in nm23‐H1 immunoreactivity (7/8 cases; 88%). This difference In nm23‐H1 expression was statistically significant (P = 0.0006; Chi‐squared test with continuity correction). All of the cases with wart virus Infection (N = 5; 100%) displayed moderately strong nm23‐H1 immunostaining throughout the squamous epithelium except for the basal layer where no staining was observed. The cases that had low‐grade squamous dysplasia of the cervix (CIN Ml) (N = 7; 100%) also displayed moderate to strong nm23‐H1 Immunoreactivity In the epithelium except for the basal layer (CIN I) or the lower two‐thirds of the epithelium (CIN II). nm23‐H1 Immunoreactivity was either absent or was significantly reduced in all of the high‐grade CIN (CIN III) cases (At = 7; 100%) in which only the non‐dysplastJc superficial third of the squamous epithelium displayed nm23‐H1 immunolabeling. The difference in nm23‐H1 expression between low‐grade and high‐grade CIN cases was statistically significant (P = 0.0013; Chi‐squared test with continuity correction). Similarly, the difference between low‐grade CIN and SCC cases in the expression of nm23‐H1 was also significant (P = 0.0041; Chi‐squared test with continuity correction). However, no statistically significant difference in nm23‐H1 immunoreactivity was found between cases of high‐grade CIN and SCC. In conclusion, nm23‐H1 protein immunoreactivity is reduced in high‐grade CIN and cervical SCC but not in low‐grade CIN. These findings suggest that reduced expression of the protein may be Important early in the sequential development of cervical squamous neoplasia.