Biomedical subjects
Publications and source records attributed to Tetsuya Murata.
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A pathologists' assistant (PA) is recognized as a well-trained clinical technologist in pathologic examinations. Some nations including the United States and United Kingdom have developed such roles with good results. In Japan, there are some serious problems with the PA system. The most important problem is the limitation of activity, such as cutting specimens and screening biopsy samples. The latter probably conflicts with Japanese medical law. Although a PA system would relieve the burden on pathologists it should be careful to introduce of a PA system in Japan.
It was hypothesized that four histopathological types or subtypes of breast carcinoma were undifferentiated types characterized by bidirectional differentiation toward both luminal epithelial and myoepithelial cells and had characteristic molecular changes: invasive ductal carcinoma (IDC) with a large central acellular zone, atypical medullary carcinoma (a subgroup in Grade 3 solid-tubular carcinoma), matrix-producing carcinoma, and spindle-cell carcinoma (or carcinoma with spindle-cell metaplasia). In 32 cases of the undifferentiated type and 37 cases of the relatively differentiated types, we immunohistochemically examined the expressions of myoepithelial markers and KIT, epidermal growth factor receptor (EGFR), and c-erbB-2 oncoproteins. Vimentin, S-100, and alpha-smooth muscle actin were positive in 28 (88%), 22 (69%), and 15 (47%) of the undifferentiated types, but were positive in seven (19%), one (3%), and one (3%) of relatively differentiated types (P < 0.0001). KIT and EGFR overexpressions were detected more frequently in the undifferentiated types (34 and 88%, respectively) than in relatively differentiated types (3 and 3%, respectively) (P < 0.0001, for both). In 11 (85%) of 13 cases with KIT overexpression, EGFR overexpression concurred. c-erbB-2 overexpression was almost equally detected in both the undifferentiated and relatively differentiated types, and did not correlate with KIT or EGFR overexpression. Phosphotyrosine was detected in 16 (67%) of 24 cases with KIT, EGFR, and/or c-erbB-2 overexpression but only in six (18%) of 34 cases without KIT, EGFR, or c-erbB-2 overexpression (P = 0.0002). The undifferentiated-type breast carcinomas appeared to show mammary epithelial stem cell-like features, and they could be identified by KIT and/or EGFR overexpressions.
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Kuttner tumor (known as chronic sclerosing sialadenitis) is a totally benign inflammatory lesion and to date there has been no report of malignancy. However, because of its clinical features, the clinical diagnosis is often that of a salivary gland neoplasm. We report a case of Kuttner tumor and discuss its differential diagnosis, especially the pathological diagnosis. Kuttner tumor may be mainly due to T lymphocyte immune reaction and of itself is a benign lesion, but it may provide a state in which a malignant lesion arises.
We managed a peculiar case of lymphoma showing immunohistochemical overexpression of cyclin D1. At initial examination the patient had meningeal lymphomatosis and general lymphadenopathy. Histologic examination of biopsy specimens of inguinal lymph nodes showed tumor cells and vague nodular growth resembling lymphoblasts. The results of flow cytometric analysis were positive for CD10, CD20, CD103, and immunoglobulin G (IgG) and Ig kappa and were negative for CD5, CD23, and terminal deoxynucleotidyl transferase activity. Results of immunohistochemical analysis of paraffin-embedded specimens were positive for cyclin D1 and Bcl2 in the tumor cells. Sixty percent of tumor cells had positive results for MIB1/Ki67. Cytogenetic and molecular studies revealed tumor cells simultaneously had t(14;18)(q32;q21), t(11;22)(q13;q11), t(8;14)(q24;q32), and t(3;14)(q27;q32) with the rearrangement of BCL1, BCL2, BCL6, and c-MYC genes. Lymphadenopathy showed a quick and complete response to doxorubicin-containing systemic chemotherapy with rituximab, but the central nervous system disease progressed and killed the patient.
The use of neoadjuvant chemotherapy for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors, especially for patients with Stage IV b (Japan criteria). We report our experience with a six-drug chemotherapeutic regimen that resulted in sufficient downstaging of the tumor in some patients to justify surgical resection. From Jan. 2001 through December 2003, 6 patients received 5-FU as a continuous infusion (200 mg/m2/day), calcium leucovorin weekly by intravenous bolus injection (30 mg/m2), mitomycin-C every 6 weeks (10 mg/m2 intravenously), and dipyridamole daily orally (75 mg), according to the UCLA regimen and gemcitabine weekly (600 mg/m2) and heparin as a continuous infusion (0-3,000 U/day) for locally advanced unresected pancreatic cancer. All of these patients were evaluable for response and survival. There were 5 partial responses (83% response rate) and 1 no response. Four of 5 responding patients had sufficient tumor regression to meet clinical criteria for resectability, three of whom underwent a curative resection. All patients who underwent downstage operation were still alive for the follow-up period (4-23 months).
The methylation status of 7 genes was examined in four cell lines, 36 samples of benign prostatic hyperplasia (BPH), 20 samples of prostatic intraepithelial neoplasia (PIN) and 109 samples of prostate cancer (PCa), using methylation-specific PCR (MSP): the pi-class glutathione S-transferase (GSTP1), retinoic acid receptor beta 2(RARbeta2), androgen receptor (AR), death-associated protein kinase (DAPK), tissue inhibitor of metalloproteinase-3 (TIMP-3), O(6)-methylguanine DNA methyltransferase (MGMT), and hypermethylated in cancer-1 (HIC-1). The frequencies of methylation in PCa were 88% for GSTP1, 78% for RARbeta2, 36% for DAPK, 15% for AR, 6% for TIMP-3, and 2% for MGMT, whereas the values were 11% for AR and DAPK, 6% for TIMP-3, 3% for GSTP1, and 0 for RARbeta2 and MGMT in BPH. Aberrant methylation of the GSTP1 and RARbeta2 genes was detected in 30% and 20% of PIN, respectively. Most samples of BPH and PCa were positive for HIC-1 methylation. Regarding accumulation of methylated cancer-related genes, there were significant correlations between PCa and BPH as well as PIN and BPH. In the present study, a high frequency of aberrant promoter methylation of the GSTP1 and RARbeta2 genes was noted in PCa. Our findings suggest that methylation of cancer-related genes may be involved in carcinogenesis of the prostate.
Primary carcinoid tumor of the testis only accounts for 0.2% of all carcinoid tumors in Japan. The clinicopathological features, including differences between Japanese and Europe/United States (Eur/US) series', which are known in ovarian carcinoids, have not yet been sufficiently recognized. In the present study, five testicular carcinoids from various clinicopathological viewpoints were analyzed, with a review of the literature. All 15 cases in Japan, including 10 previously reported, were insular carcinoids. Three of the 15 cases (20%) were associated with a teratoma. Serotonin production was confirmed in at least 10 cases (five cases in the present study and five cases in previous studies), but carcinoid syndrome was present in only two cases. Three of the 15 cases (20%) showed distant metastases, and the tumors that metastasized were larger than those that did not. These features were almost similar to those observed in the Eur/US series. Three pure carcinoids were also studied for the number of sex chromosomes by fluorescence in situ hybridization (FISH). They did not show a significant numerical abnormality of the X chromosome, which is common in testicular germ cell tumors. Therefore, the genetic background of pure carcinoids might be different from that of common germ cell tumors.
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The chromosome aberration t(7;11)(p15;p15) is uncommon but recurrent in leukemia. We experienced a case of acute leukemia with t(7;11)(p15;p15), the hematological appearance of which mimicked myeloid crisis in chronic myeloid leukemia (CML). This case showed splenomegaly, a decreased neutrophil alkaline phosphatase (NAP) score, increased vitamin B12 value, and cells at all stages of neutrophilic maturation in both bone marrow and peripheral blood. We initially had difficulty differentiating acute myeloid leukemia (AML) M2 with marked myeloid differentiation from myeloid crisis of Philadelphia chromosome (Ph)-negative CML. Immature myeloid cells in the peripheral blood disappeared and cytogenetic analysis indicated that marrow cells changed to the normal karyotype after remission induction therapy. Therefore, this case was thought not to be myeloid crisis but AML M2 subtype. The NUP98/HOXA9 fusion transcript was detected by reverse transcription-polymerase chain reaction (RT-PCR) at exon A but not exon B of NUP98.
A case of anthracosis of the esophagus is reported. The patient was a previously healthy 69-year-old Japanese woman. A black and slightly elevated lesion was detected in her esophagus by upper gastroesophageal fiberoscopic examination. Endoscopically, the lesion looked like malignant melanoma. Thoracic esophagotomy was then performed. Histological examination revealed a pigmented lesion beneath the mucosal epithelial layer. The lesion consisted of an aggregation of histiocytes containing an abundance of tiny black pigments. A few mature lymphocytes and plasma cells were also evident in the periphery of the lesion. Histologically, these findings looked like lymph nodes in the pulmonary hilus; however, no lymph nodal structure was evident in the esophageal wall. Traction diverticula were also noted in the pigmented lesion. The patient has remained well without disease for 9 months since the surgery. Although anthracosis is a rare condition in the esophagus, the present case gave warning to pathologists and clinicians that it does indeed occur. Endoscopists and pathologists should differentiate anthracosis from malignant melanoma because the treatment and outcome are quite different for each.
It is generally agreed that the autogenous bone flap which has been removed at the time of external decompression would be superior to any artificial material if it can be used in cranioplasty. Cranioplasty using autogenous frozen bone graft has been reported and showed good results except for infection and severe bone absorption. We conducted 39 cases of cranioplasty with cryopreserved autogenous bone in the presence of 10% of Dimethylsulfoxide (DMSO), which has been reported as a cryoprotective agent. Although no remarkable histological effects have been recognized in frozen bone with or without DMSO, we have obtained excellent clinical results without bone absorption in 24 of the cases. These results suggest that DMSO is helpful for frozen bone preservation.
Carcinogenesis of the prostate involves androgen influences, and associations between genetic polymorphisms of androgen receptor and metabolizing enzymes and prostate cancer risk have been reported. Roles for non-androgenic hormones are not well defined, but they also may have an impact judging from epidemiological and animal experimental alphalambda zeta of data. The purpose of the study was to determine whether hormone-related polymorphisms are associated with prostate cancer risk. A case-control study was performed with 147 Japanese prostate cancer patients and 266 urological controls. Polymorphisms of target genes [cytochrome P450 (CYP) 1B1, Leu432Val; debrisoquine hydroxylase, (CYP2D6)*4; aromatase (CYP19), Arg264Cys; estrogen receptor (ER)alpha-Xx (Xba I) and Pp (Pvu II); ERbeta-Rr (Rsa I); progesterone receptor (PR) Alu in intron 7] were examined by PCR-based methods. The capital and small letters signify the absence and presence of restriction sites, respectively. Odds ratios (OR) were adjusted for age using multiple logistic regression analysis with SPSS Medical Pack. Among the seven examined genetic polymorphisms, significant associations between CYP1B1 Leu432Val (OR 4.80; 95% confidence interval (CI), 1.21-19.05) and Alu in intron 7 of PR (OR 4.17; 95%CI, 1.26-13.85) were found. As for combined effects, the CYP1B1 polymorphisms (Leu/Val+Val/Val) together with heterozygosity for Alu in the PR were more frequent among prostate cancer patients (1.45%) than controls (0.41%), although without significance (OR, 3.99; 95%CI, 0.36-44.8). The combination of ERalpha (P/p+p/p) polymorphisms with heterozygosity for Alu in the PR demonstrated an OR of 4.56 (95%CI, 1.01-20.6). This pilot study showed that CYP1B1 and PR polymorphisms, alone or in combination, might be associated with prostate cancer risk. They might, therefore, have potential as a tool for identifying high-risk individuals.