Ryusuke Terada

Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer

Heat shock proteins (Hsp) 70 and Hsp 40 are stress proteins that cooperate as chaperones in mammalian cells. We determined the expression of Hsp 70 and Hsp 40 in 81 gastric cancers. Immunoreactivities to Hsp 70 and Hsp 40 were detected in 67.9 and 22.2% of tumors, respectively. Immunohistochemical analysis showed enhanced Hsp 70 and Hsp 40 expression in gastric tumor tissue, relative to the surrounding normal tissue. Overexpression of Hsp 70 and Hsp 40 was also confirmed by immunoblotting. Among various clinicopathological parameters, low histopathological differentiation was associated with reduced expression of both proteins.

Higher frequencies of numerical aberrations of chromosome 17 in primary gastric cancers are associated with lymph node metastasis

Abstract: We investigated the correlation between the frequency of numerical aberrations of chromosome 17 and clinicopathological features of gastric cancer. The copy number of chromosome 17 was examined with fluorescence in-situ hybridization (FISH) in frozen specimens from 100 primary gastric cancers. Chromosomal numerical aberrations were diagnosed as chromosomal loss (single signal) or gain (triple or more signals), in each cell. The frequency of numerical aberrations of chromosome 17 correlated significantly with the depth of invasion (P < 0.01), lymph node metastasis (P < 0.0001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.01). Numerical aberrations of chromosome 17 were associated with lymph node metastasis in 32 early gastric cancers. Multiple regression analysis identified the depth of invasion and numerical aberrations of chromosome 17 as independent significant determinants of lymph node metastasis. Our findings suggest that alterations in chromosome 17 may be linked with tumor progression in primary gastric cancer.Our results also indicate that numerical aberrations of chromosome 17 detected by FISH provide important information about the malignant potential (in particular, lymph node metastasis) of primary gastric cancer.

Clinical and histopathological features of colonic stromal tumor in a child

Abstract: Neoplasms of the colonic submucosa are rare in children. Gastrointestinal stromal tumors (GISTs) are undifferentiated tumors, usually diagnosed by immunohistochemistry. We report a 4-year-old girl with a submucosal GIST of the ascending colon, which was detected by computed tomography. Diagnosis after ileocecal resection was established by histology. In addition, sections were examined immunohistochemically, using antibodies against vimentin, desmin, α-smooth muscle actin, S100, neuron-specific enolase, c-kit, and CD34. Hematoxylin and eosin-stained sections showed interlacing fascicles with occasional palisades of epithelioid and spindle cells. The tumor cells were positive for vimentin and CD34. To our knowledge, this is the first reported case of colonic stromal tumor in a child.

Clinical significance of nm23 expression and chromosome 17 numerical aberrations in primary gastric cancer

The metastasis suppressor gene nm23 located on chromosome 17 might be one of the targets in deletions of chromosome 17. In this study, we analyzed the expression of nm23 and chromsome 17 aberrations in gastric cancer and assessed their clinicopathological and prognostic significance. In 103 gastric cancer patients, we examined nm23 expression by immunohistochemistry and detected chromosome 17 aberrations by fluorescence in situ hybridization. There was a significant difference in the expression of nm23 among differentiated histologic types (well>moderately>poorly) (p<0.01). Negative expression of nm23 correlated with depth of invasion (p<0.01), lymph node metastasis (p<0.05), lymphatic invasion (p<0.05), venous invasion (p<0.05), poor prognosis (p<0.05), and chromosome 17 loss (p<0.05). Chromosome 17 aberrations broadly correlated with clinicopathological variables and were associated with poor prognosis (p<0.05). Univariate analyses identified nm23 (p<0.05), chromosome 17 aberrations (p<0.05), tumor size (p<0.01), depth of invasion (p<0.0001), lymph node metastasis (P<0.001), hepatic metastasis (p<0.01), peritoneal dissemination (p<0.01), and lymphatic invasion (p<0.01) as significant prognostic factors. Multivariate analysis showed that expression of nm23 and chromosome 17 aberrations were not independent prognostic indicators. Our results indicate that negative expression of nm23 and chromosome 17 numerical aberrations correlate with tumor progression and poor prognosis but are not independent prognostic indicators.

Evaluation of Metastatic Potential of Gastric Tumors by Staining for Proliferating Cell Nuclear Antigen and Chromosome 17 Numerical Aberrations

Background: Aberrations in chromosome 17 are important in carcinogenesis. We recently reported that numerical aberrations in chromosome 17 were associated with tumor progression in gastric cancer. The aim of this study was to determine the biological characteristics of gastric tumor cells with chromosome 17 numerical aberrations.Methods: Gastric tumor sections (n = 105) and metastatic lymph nodes (n = 16) were stained simultaneously for PCNA (proliferating cell nuclear antigen) and chromosome 17 centromere. Cancers were classified as follows: Group 1: PCNA(+) and numerical chromosomal aberration(+); Group 2: PCNA(−) and numerical chromosomal aberration(+); Group 3: PCNA(+) and numerical chromosomal aberration(−); and Group 4: PCNA(−) and numerical chromosomal aberration(−).Results: The frequency of Group 1 cells correlated with lymphatic invasion (P < .0001), lymph node metastasis (P < .0001), and venous invasion (P < .01). The frequency of these cells in gastric lesions was lower than in metastatic lymph nodes (P < .01). Logistic regression analysis identified the depth of invasion followed by the frequency of Group 1 cells were two of the most significant independent factors that could predict lymph node metastasis and lymphatic invasion.Conclusions: The frequency of gastric tumor cells positive for PCNA and chromosome 17 numerical aberrations may be an indicator of the metastatic potential of gastric cancers.

Chromosome 8 numerical aberrations in stage II invasive ductal carcinoma: correlation with patient outcome and poor prognosis.

Aberrations in chromosome 8 are common in breast cancer. However, the relationship between numerical aberrations of chromosome 8 and clinical behavior (especially prognosis) in breast cancer is not well understood. In this study, a total of 40 specimens of stage II invasive ductal carcinomas (IDCs) was analyzed by fluorescence in situ hybridization (FISH) with a chromosome 8 centromere-specific probe and DNA flow cytometry (stage IIA: 20 cases; stage IIB: 20 cases). All cases were followed for at least 5.7 yr (mean: 7.5 yr; median: 7.7 yr) after surgery or until death. Single (loss), double, and triple or more signals (gain) of chromosome 8 were found in 7.6±3.5% (range: 2–16%; median: 7%), 53.7±13.2% (range: 25–81%, median: 53%), and 38.7±13.2% (range: 17–65%, median: 38%), respectively, of tumors. The frequencies of chromosome 8 gain and disomy correlated with patient outcome (respectively p<0.05 and p<0.01). When median ratios of chromosome 8 loss, disomy, and gain were used as the cutoff values, the survival curves revealed that patients in the low-frequency group survived significantly longer than those in the high-frequency group for chromosome 8 gain (p<0.05), and patients in the high-frequency group survived significantly longer than those in the low-frequency group for chromosome 8 disomy (p<0.05). Poor prognosis was not associated with age, tumor size, lymph node metastasis, histologic type, TNM stage, estrogen-receptor status, progesterone-receptor status, or DNA ploidy. Our results suggest that the frequencies of chromosome 8 gain and disomy is a potentially useful parameter for predicting prognosis of stage II IDCs.

Small nonfunctioning islet cell tumor in the body of the pancreas: report of a case.

Islet cell tumors of the pancreas are uncommon, and nonfunctioning tumors are even rarer than functioning ones. We report the case of a 67-year-old woman with a small nonfunctioning islet cell tumor, 6 × 5 mm in diameter, which was detected incidentally by ultrasonography, and subsequently confirmed by double-helical computed tomography. Diagnosis was established by histopathological examination after 80% distal pancreatectomy with splenectomy, and by various laboratory tests. Histologically, the islet cell tumor showed highly cellular spindle or epithelioid cells, which were positive for Grimelius stain. Immunohistochemical examination revealed that the tumor cells were positive for chromogranin A, but negative for somatostatin, insulin, glucagon, and gastrin. Its small size, location, and benignity make this a very rare type of nonfunctioning islet cell tumor.