Taizou Shiraishi

Mitogen-activated protein kinase pathway is involved in α6 integrin gene expression in androgen-independent prostate cancer cells: role of proximal Sp1 consensus sequence

Metastatic diseases of prostate cancer reveal high expression of alpha6 integrin and the activation of mitogen-activated protein kinases (MAP kinase). Therefore, the present study was conducted to examine whether MAP kinase pathway is involved in the alpha6 integrin gene expression in androgen-independent prostate cancer cell lines. alpha6 integrin mRNA expression, the alpha6 integrin promoter-induced luciferase activities and MAP kinase enzyme activities in androgen-independent LNCaP and PC-3 cell lines were higher than those in androgen-dependent LNCaP. Deletion and mutation analysis showed that Sp1 consensus sequence at -48 to -43 bp from the transcription start site was necessary for basal promoter activity. Binding of Sp1 to its consensus sequence in three cell lines was confirmed by electrophoretic mobility shift assays. Sp1 binding to its consensus sequence, as well as promoter activity and mRNA expression, were found to be inhibited by an inhibitor of MAP kinase kinase 1 and 2, U0126, in the androgen-independent cell lines. Our results indicate that the proximal Sp1 is necessary for basal promoter activity of the alpha6 integrin, suggesting that signal transduction from MAP kinases to activation of Sp1 might be involved in alpha6 integrin gene expression in androgen-independent prostate cancer cell lines.

New diagnostic reporting format for endometrial cytology based on cytoarchitectural criteria

Objective:  The aim of this study was to develop a new reporting format for endometrial cytology that would standardize the diagnostic criteria and the terminology used for reporting.

Does presence of prostate cancer affect serum testosterone levels in clinically localized prostate cancer patients

The relationships between serum level of testosterone (T) and prostate cancer (PCa) are complex. The present study evaluated whether presence of PCa alters serum T levels. Subjects were 125 patients with clinically localized PCa treated using radical prostatectomy (RP), for whom pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment prostate-specific antigen, Gleason score and pathological stage. Serum T and human luteinizing hormone (LH) levels before and after RP were then compared in 118 of the 125 patients. Mean pretreatment T level was significantly higher in patients with organ-confined PCa (pT2; 4.03±1.50 ng ml−1) than in patients with nonorgan-confined cancer (pT3; 3.42±1.06 ng ml−1; P=0.0438). No association existed between pretreatment serum T level and pathological Gleason score. After RP, serum T level (5.60±1.90 ng ml−1) was significantly elevated compared to preoperative level (3.89±1.43 ng ml−1; P<0.0001). In parallel, significant increases were seen in postoperative serum LH level (6.86±3.64 ng ml−1) compared to preoperative level (5.11±2.47 ng ml−1; P=0.0001). In contrast, differences in serum T levels according to pathological stage disappeared postoperatively (P=0.5513). Significant increases in serum T and LH levels were seen after RP, compared to preoperative levels in parallel. This study suggests that serum T levels are altered by the presence of PCa, supporting the possibility that PCa may inhibit serum T levels with negative feedback in the hypothalamic–pituitary axis.

Morphological characteristics of basal-like subtype of breast carcinoma with special reference to cytopathological features

Expression profiling of invasive breast carcinomas by DNA microarray techniques has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpression, and basal-like) that are associated with different clinical outcomes and with different chemotherapy. Basal-like carcinoma is associated with younger patient age, high histological grade, aggressive clinical course, development of distant metastasis, poor prognosis, and relatively high mortality rate. Basal-like carcinomas do not express estrogen receptor, progesterone receptor, or HER2 (triple-negative phenotype). Therefore, patients with basal-like carcinomas are not likely to benefit from endocrine therapies or trastuzumab, but are likely to benefit from systemic chemotherapy. Although genetic, morphological, and immunohistochemical features of basal-like carcinomas have been reported, there is no universal definition for those tumors. Furthermore, there are no specific morphological and immunohistochemical features that can identify those tumors in routine diagnostic materials. In the present paper, we present data of histological and cytological features of basal-like breast carcinoma, and discuss about its morphological spectrum.

Anaplastic transformation from papillary thyroid carcinoma with increased serum CA19-9

A 24‐year‐old woman presented with anaplastic transformation from papillary thyroid carcinoma with increased serum CA19‐9. The patient had been diagnosed as having papillary thyroid carcinoma with lung metastasis at 11 years of age. She received a total thyroidectomy with cervical lymph node dissection followed by iodine‐131 (131I) therapy over 12 years, but died due to sudden onset of rapid dissemination. Elevated serum CA19‐9 was detected in the terminal stage, and anaplastic transformation was confirmed by post‐mortem examination. Although there are few clinical reports suggesting a prognostic indicator for anaplastic thyroid carcinoma, CA19‐9 may be a useful serum marker for this tumor. Pediatr Blood Cancer 2005; 45:64–67.

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization.

Prostate-specific antigen (PSA) screening has led to a remarkable increase in prostate cancer cases undergoing operative therapy. Over half of patients with locally advanced cancer (≧pT3) develop rising PSA levels (biochemical failure) within 10 years. It is very difficult to predict which patients will progress rapidly to advanced disease following biochemical failure (BF). Therefore, a more useful prognostic factor is needed to suggest the most appropriate therapies for each patient. To determine chromosomal aberrations, we examined 30 patients with stage pT2 or pT3 primary prostate adenocarcinomas and no metastases (pN0M0) by comparative genomic hybridization (CGH). Laser capture microdissection (LCM) was used to gather cancer cells from frozen prostate specimens. Common chromosomal alterations included losses on 2q23–24, 4q26–28, 6q14–22, 8p12–22 and 13q21–31, as well as gains on 1p32–36, 6p21 and 17q21–22. Losses at 8p12–22 and 13q21–31 were observed more frequently in pT3 than pT2 tumors (P<0.05 and P<0.01, respectively). Losses at 8p12–22 were more frequent in tumors with BF (P<0.05), and those at 13q12–21 were more frequent in tumors with Gleason score (GS) 7 or more than lower GS (P<0.05). These findings suggest that losses of 8p12–22 and 13q21–31 are important determinants of prostate cancer progression.

Epithelial Bmp (Bone morphogenetic protein) signaling for bulbourethral gland development: A mouse model for congenital cystic dilation

The bulbourethral gland (BUG) is a male‐specific organ, which secretes part of the semen fluid. As the BUG is located in the deep pelvic floor, its developmental process is still unclear. Bone morphogenetic protein (Bmp) signaling plays pivotal roles in various organs. However, the function of Bmp signaling for BUG development is still unclear. The present study aimed to elucidate the role of Bmp signaling in the development of the BUG. We observed the prominent nuclear accumulation of phosphorylated (p) SMAD1/5/8, the downstream molecules of Bmp signaling, during BUG epithelial development. These results suggest that Bmp signaling contributes to BUG development. Bmp receptor1a (Bmpr1a) is known as the major type 1 signal transducer in some organogeneses. To analyze the Bmp signaling function for BUG development, we examined epithelial cell‐specific Bmpr1a gene conditional mutant mice utilizing the tamoxifen‐inducible Cre recombinase system. We observed cystic dilation and epithelial hyperplasia of the BUG in the Bmpr1a conditional knockout mice. The mutant cystic BUG specimens also showed inflammatory lesions. These BUG abnormalities resembled some of the BUG malformations observed in human congenital syndromes. The current study suggests that Bmp signaling possesses an essential role in BUG development and homeostasis. This would be the first report showing that the mutation of the Bmpr1a gene in the BUG epithelia phenocopied some abnormalities of human congenital syndromes affecting the BUG duct.

Clinicopathological factors affecting survival and recurrence after initial hepatectomy in non-B non-C hepatocellular carcinoma patients with comparison to hepatitis B or C virus.

We evaluated clinicopathological factors affecting survival and recurrence after initial hepatectomy in non-B non-C (NBNC) hepatocellular carcinoma (HCC) patients with comparison to hepatitis B or C virus, paying attention to relationship between alcohol consumption and histopathological findings. The medical records on the 201HCC patients who underwent initial hepatectomy between January 2000 and April 2013 were retrospectively reviewed. NBNC patients had higher prevalence of hypertension (47.4%), diabetes mellitus (35.5%), alcohol consumption (>20 g/day) (61.8%), and preserved liver function than hepatitis B or C patients. The 5-year survival rate of NBNC patients (74.1%) was significantly better than hepatitis B (49.1%) or C (65.0%) patients (NBNC versus B, P = 0.031). Among the NBNC patients, there was no relationship between alcohol consumption and clinicopathological findings including nonalcoholic fatty liver disease activity score (NAS). However, the 5-year OS and RFS rates in the alcohol-unrelated NBNC patients tend to be better than in the alcohol-related. By multivariate analysis, independent factors for OS in NBNC patients were Child-Pugh B/C, intrahepatic metastasis (im), and extrahepatic recurrence. NBNC patients, who were highly associated with lifestyle-related disease and preserved liver function, had significantly better prognosis compared to hepatitis B/C patients; however, there was no association between alcohol consumption and histopathological findings.

A case of pancreatic ductal adenocarcinoma with marked infiltration with IgG4-positive cells

A 75-year-old man was diagnosed as having pancreatic ductal carcinoma containing remarkable lymphocytic and plasma cell infiltration, as revealed by the cytological examination of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) specimen. The EUS-FNA specimen showed small amounts of atypical epithelium with noticeable lymphocytes and plasma cells. A pancreatic resection was performed, and the histopathological features showed an invasive pancreatic ductal carcinoma with autoimmune pancreatitis (AIP) lymphoplasmacytic sclerosing pancreatitis (LPSP)-like lesions. Most of the plasma cells were immunoreactive to anti-IgG4 antibody. EUS-FNA may be necessary for the differential diagnosis of AIP and pancreatic cancer, and close attention should be given to the presence of marked lymphoplasmacytic cells in EUS-FNA specimens while making the diagnosis.

Cytological findings of an ectopic pancreas of the stomach obtained at endoscopic ultrasound-guided fine needle aspiration, differential diagnosis from acinar cell carcinoma: a case report.

An ectopic pancreas occurs in various sites of the gastrointestinal tract, such as the gastroesophageal junction, gastric antrum and jejunum. Because an ectopic pancreas tends to present as a submucosal mass, its clinical differential diagnosis includes a gastrointestinal stromal tumour (GIST) and neuroendocrine tumour (NET). Also, pancreatic-type acinar cell carcinoma (ACC) has been reported to occur in the stomach. Therefore, this should also be considered in the differential diagnosis. A few reports about the cytological findings of an ectopic pancreas using endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) have been published. Herein, we present a case of an ectopic pancreas of the stomach that was obtained using EUS-FNA, and discuss the cytological differential diagnosis from ACC.