[Show abstract][Hide abstract] ABSTRACT: We compared claudin-4 with Ber-EP4 and carcinoembryonic antigen as markers to distinguish mesothelioma from lung adenocarcinoma, poorly differentiated lung squamous cell carcinoma, and serous adenocarcinoma of the uterus or ovary. All mesothelioma specimens were negative for claudin-4, but 3 of 18 specimens were focally positive for Ber-EP4. In contrast, lung adenocarcinoma including poorly differentiated adenocarcinoma was highly positive for claudin-4, but expression of Ber-EP4 and carcinoembryonic antigen varied widely. Claudin-4 in poorly differentiated squamous cell carcinoma had a lower positive expression rate than in adenocarcinoma. Granular claudin-4 immunoreactivity was conspicuous in poorly differentiated squamous cell carcinoma; this immunoreactive pattern was also observed in mesothelioma. Claudin-4 was thus considered very useful marker for distinguishing mesothelioma and adenocarcinoma, even if histological specimens are small, as in biopsies that contain limited numbers of tumor cells. However, it should be mentioned that claudin-4 has a limit in discrimination between squamous cell carcinoma from mesothelioma.
No preview · Article · Jun 2013 · International Journal of Surgical Pathology
[Show abstract][Hide abstract] ABSTRACT: The PTEN/PI3k/Akt pathway is a pathway in intracellular growth signal transduction that also plays an important role in the onset and progress of cancer. PTEN is a tumor suppressor that inhibits this pathway. This study examined how PTEN expression influences the prognosis of stage IV prostate cancer. Case subjects were extracted from The Queens Medical Center cancer tumor registry-database in Hawaii, USA, and included 192 stage IV prostate cancer patients that underwent androgen deprivation therapy (ADT) and who had a prostate tissue sample taken between 1992 and 2006. Of these, 133 cases under the age of 85 years whose tissue was available and could be assessed, and who did not receive anti-cancer chemotherapy, were extracted. We were able to obtain pretreatment PSA values in 108 of the 133 cases. Samples were immunohistochemically stained for PTEN and evaluated on a 4 level scale of 0, l+, 2 +, and 3 +. The relationship between the overall survival rate and age/pretreat-ment PSA value/Gleason score, and the relationship between PTEN expression and overall survival rate were statistically analyzed. The age at ADT initiation, pretreatment PSA value, and median survival period was 71.2 years, 53.4 ng/ml, and 80.4 months, respectively. A Gleason score of less than 7 accounted for 25% and 75% had a score of over 8. The ratio of PTEN 0, 1+, 2 +, and 3+ was 45%, 8%, 5%, and 42%, respectively. A correlation was found between pretreatment PSA values, Gleason score, and age in all stage IV prostate cancer cases, but there was no correlation with PTEN expression. On subdividing the 133 stage IV prostate cancer cases into the 3 stages of C, Dl, D2 of the Jewett staging system, a correlation was found between PTEN expression and the survival rate in the stage D2 group. Moreover, in stage D2 prostate cancer, a significant difference between the Gleason score and PTEN expression was observed by multivariate analysis. This suggests that strong PTEN expression may be a prognostic factor of stage D2 prostate cancer and that such an expression is an independent prognostic factor.
[Show abstract][Hide abstract] ABSTRACT: We report a non-invasive mixed mucin-producing and squamous differentiated tumor of the uterine cervix. This tumor was composed of two cell types: mucin-producing cells and non-mucin-producing cells. These cells were intimately mixed with each other, and showed intraepithelial spreading. The mucin-producing cells showed signet-ring or columnar shapes, and were localized to the lower-to-upper epithelial layer. The non-mucin-producing cells had eosinophilic cytoplasms with a monotonous appearance through the epithelium. Mitosis was sometimes observed in both cell types. Immunohistochemically, both cell types were positive for p16(INK4A) . The non-mucin-producing cells were positive for p63 and 34βE12, suggesting squamous differentiation. Although most mucin-producing cells were p63(-) , a few of them were p63(+) and many 34βE12 immunoreactive cells were found in the mucin-producing cells. This tumor was adenosquamous carcinoma in situ.
Full-text · Article · Jan 2013 · Journal of Obstetrics and Gynaecology Research
[Show abstract][Hide abstract] ABSTRACT: Mesothelioma is one of diseases that is showing an increase in incidence in recent years. The cytologic characteristics of mesothelioma are widely variable. To distinguish mesothelioma from adenocarcinoma or reactive mesothelial cells is difficult, and consequently the diagnostic accuracy by cytology is not high. Here, we analyzed the appearance ratio of intracytoplasmic vacuole cells as it seems to be a useful means to distinguish mesothelioma from reactive mesothelial cells. Body cavity effusions in 17 cases of epithelial mesothelioma and 10 cases of reactive mesothelial cells were analyzed. Intracytoplasmic vacuole cells were classified as: 1) peripheral vacuole-like (PV) cells, 2) central vacuole (CV) cells, and 3) vacuole (V) cells that lack PV and CV cell features. Comparison of the appearance of intracytoplasmic vacuole cells between mesothelioma and reactive mesothelial cells revealed that the appearance ratio of PV cells was significantly high in mesothelioma. We further analyzed the structural features of mesothelioma. Mesothelioma was subclassified into two groups; group A shows a solid cluster and group B shows a flat cluster or isolated cells, namely a non-solid cluster. Comparison of the vacuole cells in groups A and B indicated that the appearance of PV and CV cells was significantly higher in group B. These findings suggested that the appearance ratio of PV and CV cells is useful to distinguish mesothelioma from reactive mesothelial cells, particularly in cases of mesothelioma that show a fiat cluster or an isolated cell and mimic reactive mesothelial cells. Thus, when PV or CV cells are identified, intensive clinical examinations are necessary for the diagnosis of mesothelioma. The present findings provide a clue for the diagnosis of mesothelioma that may be misdiagnosed as reactive mesothelial cells in effusion cytology.
[Show abstract][Hide abstract] ABSTRACT: In diffuse large B-cell lymphoma (DLBCL), a CD20-negative relapse is clinically significant because it is associated with chemo-refractory phenotypes and loss of a therapeutic target. The alteration of the CD20 gene is reported as infrequent in CD20-negative relapse in B-cell lymphoma. We established a DLBCL cell line with loss of CD20 expression (SD07) from a patient at CD20-negative relapse. She was initially diagnosed with CD20-positive DLBCL and received repeated immuno-chemotherapy that included rituximab. SD07, which has an immunoglobulin κ rearrangement identical to that of lymphoma cells at CD20-negative relapse, showed homozygous deletion of the CD20 gene with loss of the copy number of 11q12. SD07 is the first case in which it is proven that the loss of CD20 expression in relapsed DLBCL is the result of deletion of the CD20 gene. Deletion of the CD20 gene is a molecular mechanism of CD20-negative relapse in a subset of DLBCL.
No preview · Article · Jul 2012 · European Journal Of Haematology
[Show abstract][Hide abstract] ABSTRACT: Human intestinal spirochetosis is a common condition in Western countries, but it is not well recognized in Japan. To determine the incidence and clinicopathologic findings of human intestinal spirochetosis in Japan, we performed a prospective study of a series of endoscopically resected biopsy specimens of the large intestine over a 4-month period at a single hospital located in Tokyo, Japan. Among 1025 samples, 42 cases of human intestinal spirochetosis were detected (4.1%). Genomic DNA from formalin-fixed paraffin-embedded biopsy specimen, tissue samples was subjected to polymerase chain reaction analysis for the detection of two strains of spirochetes (Brachyspira aalborgi and Brachyspira pilosicoli) by amplifying species-specific portions of the NADH oxidase gene and 16S ribo-somal RNA. B. aalborgi and B. pilosicoli were detected in 37 and 8 cases, respectively, with 5 cases having dual infection of both species. These results from a precise prospective study suggest that intestinal spirochetosis infection in Japan is not rare, and that the incidence is similar to that in Western countries. This finding differs from those of several retrospective studies that have claimed that the prevalence of intestinal spirochetosis is extremely low in Japan. In the current study, most cases of intestinal spirochetosis were asymptomatic, and the cases with digestive symptoms among the 1025 samples did not show any correlation with the status of intestinal spirochetosis infection. These results suggest that human intestinal spirochetosis infection is not pathogenic, but it is an incidental and/or indigenous infection that does not require treatment.
[Show abstract][Hide abstract] ABSTRACT: We report on three cases of ulcerative colitis who presented with increased levels of serum carcinoembryonic antigen (CEA) during the active stage. All cases were pancolitis with a moderate to severe disease course. After remission induction with medical therapies, serum CEA levels decreased to the normal reference range. Immunohistochemical analyses demonstrated the existence of CEA not only along with the apical surface of the colonic epithelia but also at the cytosol of the inflamed epithelia where goblet cells were depleted during the active stage. We speculate that CEA was up-regulated by inflammatory response particularly in the process of epithelial regeneration.
No preview · Article · Apr 2012 · Clinical Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: T/NK cells are involved in approximately 85% of primary cutaneous lymphomas, and more than half of the cases are mycosis fungoides (MF) and Sezary syndrome. Primary cutaneous lymphoma is classified functionally based on clinical behavior, histology and surface characteristics; the diagnostic rate has improved due to implementation of clonality analysis. We examined the progression to lymphoma in 14 cases that were clinicopathologically diagnosed as lichen planus (LP); 18 as parapsoriasis en plaques (PP), an inflammatory disorder; and 8 (28 samples) as MF in Showa University Hospital from 1993 to 2011. Immunohistochemical staining was performed on all samples, and PP and MF samples were further examined by clonality analysis. Dissociation of CD4/CD8 was not found in any LP samples, but was revealed in 33% of PP and 88% of MF samples. There was a strong tendency for a decrease of CD7 in PP and MF samples. CCR3 was negative in all LP, PP, and MF samples. CCR4 and CXCR3 were positive in many more PP and MF samples, compared with LP samples. All of the PP samples were negative in the T-cell clonality analysis, but 50% of MF samples were positive. These results suggest that the surface properties of PP are closer to those of MF, rather than LP. Therefore, PP may also have the potential for tumorous change, in addition to being an inflammatory skin disease. Moreover, the validity of the clonality analysis in auxiliary diagnosis of MF should be checked further.
[Show abstract][Hide abstract] ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is one of the most common lymphoid neoplasms, characterized by heterogeneity in the clinical, immunophenotypic, and genetic features. The proliferation and progression of neoplastic cells are known to be closely related to abnormalities in various positive and negative cell-cycle regulators. Skp2 positively regulates the Gl-S transition by promoting degradation of the cyclin-dependent kinase inhibitor p27. Skp2 is frequently overexpressed in a variety of cancer cells and has been implicated in oncogenesis. In this study, we performed immunohistochemical analysis of the cell cycle-associated proteins, Skp2, p27, and Ki-67, in 33 patients with diffuse large B-cell lymphoma (DLBCL), and evaluated the correlation between the clinicopathological characteristics and the expression levels of these proteins. In 33 patients, Skp2 expression was correlated with Ki-67. The patients also were classified into two groups according to the so-called "Hans classifier": Germinal centre B-cell like (GCB) type and non-GCB type. Skp2 expression correlated with Ki-67 in the non-GCB type, but not in the GCB type. There was no significant correlation between Skp2 and p27, or p27 and Ki-67. It was suggested that Skp2 is a valuable marker for predicting proliferation of neoplastic cells in DLBCL.
[Show abstract][Hide abstract] ABSTRACT: Although dysfunction of VE-cadherin-mediated adherence junctions in vascular endothelial cells (ECs) is thought to be one of the initial steps of atherosclerosis, little is known regarding how VE-cadherin is disrupted during atherogenic development. This study focused on the role of calpain, an intracellular cysteine protease, in the proteolytic disorganization of VE-cadherin and subsequent progression of atherosclerosis.
Increased expression of m-calpain was observed in aortic ECs in atherosclerotic lesions in humans and low-density lipoprotein receptor-deficient (ldlr(-/-)) mice. Furthermore, proteolytic disorganization of VE-cadherin was shown in aortic ECs in ldlr(-/-) and apolipoprotein E-deficient (apoE(-/-)) mice. Long-term administration of calpain inhibitors into these mice attenuated atherosclerotic lesion development and proinflammatory responses, as well as VE-cadherin disorganization, without normalization of plasma lipid profiles. Furthermore, in vivo transfection of m-calpain siRNA to ldlr(-/-) mice prevented disorganization of VE-cadherin and proatherogenic hyperpermeability in aortic ECs. Treatment of cultured ECs with oxidized LDL, lysophosphatidylcholine, or LDL pretreated with secreted phospholipase A(2) led to the induction of m-calpain but not of μ-calpain, thereby eliciting selective m-calpain overactivation. These data suggest that lysophosphatidylcholine-induced m-calpain directly cleaves a juxtamembrane region of VE-cadherin, resulting in dissociation of β-catenin from the VE-cadherin complex, disorganization of adherence junctions, and hyperpermeability in ECs.
Subtype-selective induction of m-calpain in aortic ECs during atherosclerotic progression is associated with proteolytic disorganization of VE-cadherin and proatherogenic hyperpermeability in cells. Thus, a strategy to selectively inhibit m-calpain may be useful for the therapeutic treatment of patients with atherosclerosis.
[Show abstract][Hide abstract] ABSTRACT: The purpose of performing pleural cauterization is developing heat denaturation, and we can induce pleural thickening and also reduce the bullae by shrinking the pleura It originates in a method of the cauterization whether there will be tissue damage. So a safe and reliable method of cauterization is required. Here, we investigated the indications for and effectiveness of cauterization techniques performed at our facility. We perform cauterization while dropping saline solution, so when using a Salient Monopolar Sealer, we can avoid excessive thermo-coagulation and more easily control cauterization. Furthermore, on the basis that only emphysematous pleura will turn white on cauterization, bullae can be distinguished, which is particularly effective in the case of lesions with unclear borders. In the case of a large emphysematous bulla, shrinkage of the bulla by cauterization can provide a sufficient surgical field, and a smaller lesion can then be stapled.
No preview · Article · Apr 2011 · Kyobu geka. The Japanese journal of thoracic surgery
[Show abstract][Hide abstract] ABSTRACT: Endoscopic examination shows that serrated neoplasias (SNs), such as serrated adenomas and sessile serrated adenomas, exhibit different mucosal crypt patterns. However, it remains unclear whether advanced serrated polyps with different mucosal crypt patterns have different clinicopathological or molecular features.
We classified the mucosal crypt patterns of 86 SNs into three types (hyperplastic, adenomatous, and mixed pattern) and evaluated their clinicopathological and molecular features.
We found significant differences in the proliferative activity status between SNs with mixed/adenomatous patterns and those with the hyperplastic patterns. SNs with the hyperplastic pattern were frequently located in the proximal colon and had a macroscopically superficial appearance, whereas SNs with the adenomatous pattern were often located in the distal colon and had a protruding appearance. Furthermore, a significant difference was observed in the frequency of the CpG island methylator phenotype (CIMP), involving the methylation of two or more CIMP-related genes (MINT1, MINT2, MINT31, p16, and MLH1), between SNs with the hyperplastic pattern and those with the mixed/adenomatous patterns (18/32 (56%) vs. 8/28 (29%) or 7/26 (27%); P=0.0309 or P=0.0249, respectively). Moreover, the prevalence of KRAS mutations was significantly higher in SNs with the adenomatous pattern than in those with the hyperplastic pattern (7/26 (27%) vs. 1/32 (3%); P=0.0173). In comparison with other patterns, the mixed pattern was detected more frequently in mixed serrated polyps (MSPs), which contain separate histological components. Some MSPs exhibited concordant molecular alterations among the different histological components.
The clinicopathological and molecular features of SNs correlated strongly with their mucosal crypt patterns, which were observed using chromoendoscopy.
No preview · Article · Mar 2011 · The American Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Recent studies have suggested that circulating inflammatory cells augment the growth of thrombus in acute coronary syndrome (ACS). We therefore immunohistochemically analyzed thrombi in aspirates obtained from patients immediately after the onset of ACS.
Two hundred twenty samples were studied. Total thrombus area, white thrombus area, and red thrombus area were measured. As antibodies in immunohistochemical staining, myeloperoxidase (MPO), CD66b, CD68, p-selectin, tissue factor (TF) and PAI-1 were employed respectively.
The ratios of areas of red and white thrombi correlated with whole sample areas of enlarged thrombi (r = 0.48, p < 0.001). The immunohistochemical findings revealed granulocytes and macrophages aggregated around p-selectin-positive platelets that shared the boundary between white and red thrombi, a region where MPO and CD66b expression was abundant in neutrophils. The ratios (%) of MPO- and CD66b-positive cells significantly correlated with whole sample areas (r = 0.50; p < 0.001 and r = 0.49; p < 0.001, respectively). Neutrophils and macrophages within thrombi were positive for TF and PAI-1. Along the boundary between red and white thrombi, TF and PAI-1 positivity coincided with MPO-, CD66b- and CD68-positive cells. The ratios of cells positive for both TF and PAI-1 in this area significantly correlated with the whole sample area (r = 0.43, p < 0.001 and r = 0.60, p < 0.001, respectively).
These results suggested that enhanced activation of peripheral neutrophils together with increased TF and PAI-1 expression might comprise a considerable portion of thrombus enlargement.
No preview · Article · Mar 2011 · Thrombosis Research
[Show abstract][Hide abstract] ABSTRACT: Distinguishing adult T-cell leukemia/lymphoma (ATLL) from peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is pathologically difficult in the absence of clinical findings of monoclonal cells infected with human T-cell lymphotropic virus type-1 (HTLV-1). However, if the immunophenotypic difference between ATLL and PTCL-NOS is clearly identified, the pretest probability of ATLL will increase even without clinical information of HTLV-1, when distinguishing ATLL from PTCL-NOS. We clinicopathologically studied paraffin-embedded tissues of 37 patients who were diagnosed with ATLL or PTCL-NOS according to the WHO classification, 4th edition, at Showa University Hospital from November 1983 to September 2009. We analyzed the immunophenotypic differences between ATLL and PTCL-NOS by using immunohistochemistry. Significant differences between ATLL and PTCL-NOS were observed for CD7, CD25, CD56, CCR4, and TIA-1. Loss of CD7 was observed in all ATLL cases. CD25-positive cases represented 72% of the ATLL cases, i.e., more than in PTCL-NOS cases (P = 0.005). Similarly, CCR4-positive cases constituted 72% of the ATLL cases, i.e., more than in PTCL-NOS cases (P < 0.001). CD56- and TIA-1-positive cases were significantly more frequent in patients with PTCL-NOS than in patients with ATLL (CD56, P = 0.01; TIA-1, P = 0.03). Immunophenotypic evaluation for CD7, CD25, CD56, CCR4, and TIA-1 using immunohistochemistry is useful for distinguishing ATLL from PTCL-NOS. Therapies with anti-CD25 and anti-CCR4 antibodies are expected to be effective in ATLL treatment, because of high CD25- and CCR4-positive rates in ATLL patients.
[Show abstract][Hide abstract] ABSTRACT: We report a 62-year-old man who was a human T-lymphotropic virus type 1 (HTLV-1) carrier with strongyloidiasis. He was born in Okinawa, Japan, an area endemic for both Strongyloides stercoralis and HTLV-1. On admission he presented with nausea and abdominal bloating and then he developed severe respiratory distress with septic shock. S.stercoralis rhabditiform larvae were found by sputum microscopy and then he was diagnosed as a disseminated strongyloidiasis with severe pulmonary strongyloidiasis. HTLV-1 carriers are at increased risk of developing severe strongyloidiasis.
[Show abstract][Hide abstract] ABSTRACT: We retrospectively studied the clinicopathological factors of patients with T- and NK- cell neoplasms (T/NK-N) based on the 4th edition of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues in Showa University Hospital. This study included 107 patients with T/NK-N, including 25 (23.4%) with peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS); 19 (17.8%) with adult T-cell leukemia/lymphoma (ATLL); 17 (15.9%) with extranodal NK/T cell lymphoma, nasal type (ENKTL); 10 (9.3%) with angioimmunoblastic T-cell lymphoma (AITL); 9 (8.4%) with primary cutaneous CD30 positive T-cell lymphoproliferative disorders (C-CD30 + LPD); 8 (7.5%) with T lymphoblastic leukemia/lymphoma (T-ALL/LBL); 8 (7.5%) with mycosis fungoi-des (MF); 4 (3.7%) with anaplastic large cell lymphoma, ALK negative (ALCL, ALK-); and 7 with others. Among all analyzable patients, the 5-year overall survival (OS) rate was 41% and the median duration of OS was 34.8 months. Patients with C-CD30 + LPD had significantly longer survival rates than those with ATLL and AITL. Patients with a level of serum-soluble interleukin-2 receptor (sIL-2R) ≥ 1300 U/mL at diagnosis had significantly lower survival rates (P = 0.02). With the exception of ATLL patients, high sIL-2R level at diagnosis was significantly associated with reduced survival (P = 0.02). sIL-2R levels at diagnosis were lower in patients with ENKTL, C-CD30 + LPD, ALCL, ALK -, MF, and T-ALL/LBL than in those with other subtypes. At diagnosis, serum iron levels below the normal range (male, 50 μg/dL; female, 35 μg/dL) and total iron-binding capacity < 250 μg/dL were significantly associated with reduced survival (P = 0.02). Our study suggests that high sIL-2R levels and iron restriction at diagnosis are poor prognostic factors. To date, there have been no reports on the correlation of iron restriction and T/NK-N. In order to establish a prognostic model including parameters of iron metabolism, a greater number of patients should be evaluated in larger clinical trials.
[Show abstract][Hide abstract] ABSTRACT: We report on a case of a primary low-grade endometrial stromal sarcoma (ESS) that progressed to a secondary high-grade ESS. In the secondary tumor, the immunohistochemical profile and focal tumor cell proliferation pattern suggested that this tumor was not truly undifferentiated, but possessed features of endometrial stroma. Low-grade ESS of our patient's primary tumor showed p53 protein overexpression, which is unusual in low-grade ESS, and her secondary high-grade ESS showed more prominent p53 immunoreactivity. This indicates that low-grade ESS that shows p53 immunoreactivity might progress to high-grade ESS, and it is considered that such cases of low-grade ESS should pay attention to the prognosis. Immunoreactivity for epidermal growth factor receptor was observed in both tumors, suggesting a relationship between the primary and secondary tumors in our case. Further study requires more immunohistochemical data for cases in which low-grade ESS transitions to high-grade ESS; in particular, data on epidermal growth factor receptor expression are necessary to define new therapeutic strategies for ESS.
Full-text · Article · Jul 2010 · International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists