Papers - NANASHIMA Atsushi
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Sawai T., Sasano O., Tsuji T., Nanashima A., Yamaguchi H., Yasutake T., Nakagoe T., Ayabe H., Tagawa Y.
Journal of Gastroenterology 33 ( 4 ) 495 - 499 1998.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology
Numerical aberrations of chromosome 17 and nuclear DNA content were compared in patients with hereditary non-polyposis colorectal cancer (HNPCC) and those with sporadic colorectal cancer (SCRC). During a period of 22 years, 30 cases (3.2%) from 28 families satisfied the Japanese clinical criteria of HNPCC. Using freshly frozen tissue samples, we investigated chromosomal aberration with fluorescence in situ hybridization with alpha satellite DNA probe for chromosome 17. Flow cytometric quantification of nuclear DNA content showed DNA aneuploidy in 9 of 15 patients (60.0%) with HNPCC and in 160 of 234 patients (68.4%) with SCRC; there was no significant difference between HNPCC and SCRC. The mean proportion of nuclei with aneusomy 17 (numerical chromosome aberration index: NCAI) in 14 patients with HNPCC was significantly higher than that in 42 patients with SCRC (46.8 ± 5.0% vs 39.0 ± 10.3%, P < 0.01). NCAI increased in proportion with the progression of the disease in SCRC (26.1% in stage I, 33% in stage II, 38.8% in stage IIIa, 42.7% in stage IIIb, and 46.2% in stage IV, P < 0.01), whereas NCAI in HNPCC was high in all stages (43.5%-49.2%). The proportion of patients with multiple numerical aberration of chromosome 17 was significantly higher in HNPCC (9/14) than among SCRC (11/42). Our data suggest that chromosome 17 is present in an unstable condition in HNPCC.
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Nakagoe T., Fukushima K., Tuji T., Sawai T., Nanashima A., Yamaguchi H., Yasutake T., Hara S., Ayabe H., Matuo T., Kamihira S.
Cancer Detection and Prevention 22 ( 6 ) 499 - 505 1998
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancer Detection and Prevention
The expression of blood group antigens A, B, and H, as well as sialylated and nonsialylated forms of Lewis(a) and Lewis(x), was studied using immunohistochemical methods in normal and tumor tissues in the following cohort of patients: 51 patients with primary breast carcinoma, 13 with metastatic lymph node lesions, and 16 with benign tumors of the breast. As a control, normal tissue was obtained from a similar group of 22 patients with breast cancer. The noncancerous tissues expressed the same A/B/H antigens as the patients' red blood cells and also usually expressed Lewis-related antigens. Seventy-six percent of primary carcinomas failed to express the appropriate A/B/H antigens, and in one blood group A patient the tumor tissue expressed B antigen. In the metastatic lesions, Lewis(a)/sialyl Lewis(a) expression was reduced when compared with the primary tumors, but Lewis(x)/sialyl Lewis(x) antigens were still expressed. These results suggest a possible relationship between the metastatic behavior of the tumor and expression of the blood group antigens.
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Preoperative estimation of lymphatic vessel invasion on gastric carcinoma
Yasutake T., Terada R., Yamaguchi E., Tsuji T., Nanashima A., Sawai T., Yamaguchi H., Nakagoe T., Ayabe H., Tagawa Y.
Japanese Journal of Gastroenterological Surgery 31 ( 10 ) 2171 - 2175 1998
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Gastroenterological Surgery
Preoperative estimation of lymphatic invasion by gastric carcinoma was attempted by using clinicopathological or cell and molecular biological methods. In 1129 cases of gastric carcinoma, the size of cancers with lymphatic invasion (71 mm) was significantly (p<0.001) greater than that of cancers without lymphatic invasion (43 mm). Stainability of nm23 was relatively low in cases of positive for lymphatic invasion. Simultaneous attempts to detect of proliferating cell nuclear antigen (PCNA) and numerical chromosomal aberrations were also performed in 100 cases of gastric carcinoma. PCNA was detected by the immunofluorescence method using anti-PCNA antibody (PC-10) after acetone-ethanol fixatin. Numerical chromosomal aberrations were detected by fluorescence in situ hybridization (FISH) using the probe for chromosome 17 centromere. The frequency of the cells with positive PCNA staining that had numerical aberration of chromosome 17 was significantly (p = 0.0001) higher in the cases with lymphatic invasion (15.3%), compared to the cases without lymphatic invasion (9.0). The percentage of the cells that were PCNA-negative with numerical chromosomal aberrations was unrelated to lymphatic invasion. These results revealed that lymphatic vessel invasion is not induced by chromosome aberration or the cell cycle alone, but by a combination of both of them. This method can be performed preoperatively. The results also indicated that tumor size and tha rate of PCNA positivity with numerical aberration of chromosome 17 could be a marker for lymphatic invasion of gastric carcinoma.
DOI： 10.5833/jjgs.31.2171
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Right-sided predominance of superficial early cancers in synchronous multiple colorectal carcinomas
Sawai T., Tsuji T., Yamaguchi E., Nanashima A., Yamaguchi H., Yasutake T., Nakagoe T., Ayabe H.
Journal of the Japan Society of Colo-Proctology 51 ( 8 ) 567 - 572 1998
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of the Japan Society of Colo-Proctology
Between 1989 and 1996, there were 54 patients with synchronous multiple colorectal carcinomas identified in an operative series of 569 patients in the First Department of Surgery, Nagasaki University School of Medicine, for a frequency of 9.6 percent. When comparing the mean age of patients, sex distribution, histological stage, the incidence of extra colonic malignancies, and family history of malignancies in a first degree relatives, there was no significant difference between the group with and without synchronous carcinomas. The anatomical distribution of tumors in the group with synchronous carcinomas revealed a higher percentage of tumors located on right-sided colon (p < 0.05). There were higher incidences of superficial tumors, early carcinomas, well differentiation, and associated adenomatous polyps in the group with synchronous carcinomas (p < 0.00001, respectively). In 74 tumors of early colorectal carcinomas, superficial tumors were significantly more often in right-sided tumors than in left-sided-tumors (p < 0.0002). Non-polypoid growth carcinomas were also more often in right-sided- tumors than in left-sided tumors (p < 0.05). These results suggest the importance of preoperative pancolonoscopy for the identification of early carcinomas and adenomatous polyps in patients with colorectal cancer especially with right-sided tumors.
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Safety of repeated total hepatic inflow occlusion during liver resection
Yamaguchi H., Nanashima A., Hatano K., Shibasaki S., Matsuo S., Sawai T., Yasutake T., Nakagoe T., Ayabe H.
Acta Hepatologica Japonica 39 ( 11 ) 812 - 819 1998
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Acta Hepatologica Japonica
To evaluate the effect on liver due to repeated total hepatic inflow occlusion with Pringle maneuver during liver resection, we analyzed changes in hepatic venous blood of the remaining liver in 16 patients undergoing partial hepatectomy. These patients were divided into two groups as follows : chronic liver disease group consisted of the patients with cirrhosis and/or chronic hepatitis, and normal liver group consisted of the patients with no any chronic liver disease. No significant decreases were found in oxygen saturation (SvO2) between before the first clamping and 15 min after that in both group. Although HVKBR and AKBR decreased significantly 15 min after the first clamping in the chronic liver disease group, they return to the initial levels within the following 5 min of declamping. No significant differences were found in SvO2, lipid peroxide, HVKBR and AKBR between before the first clamping and 5 min after the final declamping in both groups. However, pH and HCO3-significantly decreased and PvCO2significantly increased 5 min after the final declamping in the chronic liver disease group. These results suggested that intermittent total hepatic inflow occlusion during liver surgery induces negligible or no liver damage in the patients with chronic liver disease. However, this procedure may induce a significant metabolic acidosis in these patients.
DOI： 10.2957/kanzo.39.812
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Nanashima A., Nakagoe T., Sawai T., Nakamura S., Yamaguchi H., Yasutake T., Kusano H., Ayabe H.
Diseases of the Colon and Rectum 40 ( 10 SUPPL. ) 1997.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Diseases of the Colon and Rectum
PURPOSE: Sialyl Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. We compared the proportion of specimens of flat-type colorectal cancers expressing STn with that of polypoid cancers, by examining the immunohistochemical reactivity of STn in various morphologic types of early and advanced colorectal cancers. METHODS: A total of 111 biopsies from the colorectal area were examined for STn expression, including 11 adenomas, 58 early cancers, and 42 advanced cancers. Each section was stained immunohistochemically for STn antigen. In each section, we examined STn expression in the cancer area, adjacent mucosa, and normal epithelium. RESULTS: STn expression was detected in 90.9 percent of adenomas, 36.2 percent of early cancers (T1), 64.3 percent of advanced cancers ( > T1), and 52 percent of mucosa adjacent to cancer. The morphology of cancer tissue did not influence the number of specimens exhibiting STn antigen expression in mucosa adjacent to cancer cells. STn antigen was rarely expressed in flat or depressed-type early cancers (T1; 7.1 percent), and the expression was higher in moderately than in well-differentiated adenocarcinomas. In advanced cancers ( > T1), a similar proportion of protruding and small ulcerative cancers expressed STn. CONCLUSION: Our results suggest that the low expression of STn antigen in flat-type cancers may be the result of different mechanisms of cellular transformation during carcinogenesis from the usual adenoma-carcinoma sequence in colorectal neoplasms.
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Analysis of p53 gene deletions in colorectal cancers using fluorescence in situ hybridization
Nanashima A., Tagawa Y., Yasutake T., Taniguchi Y., Sawai T., Nakagoe T., Ayabe H.
Surgery Today 27 ( 11 ) 999 - 1004 1997.11
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Surgery Today
To examine the relationship between the incidence of p53 gene deletion in each nucleus and the clinico-pathological features in colorectal cancers, we performed a cytogenetic study using fluorescence in situ hybridization (FISH). FISH was performed on 5 adenomas and 38 colorectal cancers that had been resected surgically. The nucleus, in which the copy number of the p53 signal was lower than that of chromosome 17, was determined as a deletion of the p53 gene. The mean frequency of the deletion of p53 in adenomas and cancers were 7.8% ± 3.0% and 57.0% ± 19.0%, respectively. Numerical aberrations of chromosome 17 or a deletion of p53 were also detected in DNA diploidy. The mean frequency of the deletion of p53 in 32 cases with aneusomy of chromosome 17 (65.7% ± 14.5%) was significantly higher than that in cases of disomy (51.1% ± 19.3%, P < 0.05). Even though this frequency was high in the early stage, it was not associated with any specific histopathological features. This frequency was also higher in double primary cancers (70.4% ± 16.7%) compared with single colorectal cancers (53.4% ± 18.1%) (P < 0.05). Using FISH, our results demonstrated that the clonal deletion of the p53 locus is an early genetic event of colorectal cancers and that a high incidence of p53 deletion may influence the occurrence of double primary cancers.
DOI： 10.1007/BF02385778
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Tagawa Y., Yasutake T., Sawai T., Nanashima A., Jibiki M., Morinaga M., Akama F., Nakagoe T., Ayabe H.
Clinical Cancer Research 3 ( 9 ) 1587 - 1592 1997.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Clinical Cancer Research
Numerical chromosome aberrations by interphase cytogenetic analysis have been reported in a few samples of colorectal neoplasms. No studies have defined a distinct relationship between these aberrations and clinicopathological features. To investigate the chromosome aberrations as a marker of invasiveness or prognosis, we conducted an interphase cytogenetic study using fluorescence in situ hybridization and examined 142 colerectal neoplasms consisting of 15 adenomas and 127 cancers. The target chromosomes were chromosomes 11 and 17. We also evaluated the nuclear DNA content as detected by flow cytometry, analyzed the relationship between the frequency of aneusomy and clinicopathological features, and examined the survival rate in these patients. The loss of chromosome 11 was observed in 31% of adenomas, whereas in cancers DNA aneuploidy was observed in 63% of cases, a gain of chromosome 17 was observed in 63% of cases, and a gain of chromosome 11 was observed in 42% of cases. Numerical chromosome aberrations in diploid DNA were also observed. Increased depth of invasion (≤T 3 ) and advanced Dukes' stage (≤B) of malignant tumors were associated with a higher frequency of a gain of chromosome 11 (P < 0.01 and P < 0.05, respectively). Increased depth of invasion (≤T 2 ) in cancers was associated with a higher frequency of a gain of chromosome 17 (P < 0.05). Multivariate analysis of postoperative survival showed that a loss or gain of chromosome 11 was independently associated with a poor prognosis (P < 0.05). Numerical chromosome aberrations appear prior to the alteration of nuclear DNA content as detected by flow cytometry and influence the progression of colorectal cancers. Aneusomy of chromosome 11 is associated with poor postoperative prognosis of primary colorectal cancers.
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Sawai T., Sasano O., Shibazaki S., Shibata Y., Tsuji T., Nanashima A., Yamaguchi H., Yasutake T., Hara S., Tagawa Y., Nakagoe T., Ayabe H.
Human cell : official journal of Human Cell Research Society 10 ( 3 ) 193 - 198 1997.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Human cell : official journal of Human Cell Research Society
Fluorescence in situ hybridization with biotinylated repetitive DNA probe specific for the centromeric region of chromosome 17 (p17H8: Oncor) was applied to suspended nuclei which were isolated by Shutte's method from formalin-fixed paraffin-embedded tissue. The tissues were obtained from surgically resected specimens from nine patients with non-small cell lung carcinoma. The isolated nuclei were prepared with 0.05% pepsin/0.1NHCl for 15 minutes at 37 degrees C. Subsequently, these were immersed in 70% acetic acid for 10 seconds at room temperature. After heat denature with hybridization mixture which contained 3 mu 1 DNA probe for 10 minutesat 70 degrees C, 1 x 10(6) nuclei were incubated overnight at 37 degrees C. After washing with 60% formamide/2 x SSC, the hybridized probes were labeled by FITC conjugated avidin. A number of centromeric signals of chromosome 17 wasevaluated by fluorescence microscopy (BH-2, Olympus). Furthermore, a probe-related FITC intensity was quantified using flow cytometry (FACScan, Becton Dickinson). As the results, there was good correlation between a relative fluorescence intensity determined by flow cytometry and a relative fluorescence signal by fluorescence microscopy (p < 0.05).
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Gain of chromosome 20 is a frequent aberration in liver metastasis of colorectal cancers
Nanashima A., Yamaguchi H., Yasutake T., Sawai T., Kusano H., Tagawa Y., Nakagoe T., Ayabe H.
Digestive Diseases and Sciences 42 ( 7 ) 1388 - 1393 1997.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Digestive Diseases and Sciences
To investigate the characteristics of the numerical chromosome aberrations in liver metastasis of colorectal cancers, fluorescence in situ hybridization (FISH) for chromosomes 8, 18, 14/22, and 20 was performed in 18 specimens of primary regions and 18 of metastatic regions in liver metastasis of colorectal cancers compared with 15 of non-liver metastatic cancers. Among these numerical aberrations, the gain of chromosome 20, especially copy numbers exceeding three, was frequently observed in primary and metastatic cancers. Among these numerical aberrations, the gain of chromosome 20, especially copy numbers exceeding three, was frequently observed in primary and metastatic regions of liver metastasis groups compared with that of the non-liver metastasis group (P < 0.05). The incidences of gain of chromosome 20 in both regions of the liver metastasis group were higher than that of the non-liver metastasis group (P < 0.05). The gain of chromosome 20 is a frequent aberration in primary and metastatic regions in patients with liver metastatic colorectal cancers and may be available as a genetic marker for the diagnosis or prediction of liver metastasis.
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Deletion of chromosome 11 and development of colorectal carcinoma
Nanashima A., Tagawa Y., Yasutake T., Fujise N., Kashima K., Nakagoe T., Ayabe H.
Cancer Detection and Prevention 21 ( 1 ) 7 - 11 1997.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancer Detection and Prevention
The deletion of chromosome 11q is observed frequently in tumors of the large intestine. To investigate the relationship between aberrations of chromosome 11 and histopathological features of colorectal carcinoma, we examined the frequency of chromosome aberrations using fluorescence in situ hybridization to 29 short-term cultured cells from surgical specimens. Numerical aberrations were not related to any factors. The deletion of chromosome 11 was frequently observed in larger (≤5 cm) and more invasive tumors (≤T3 category) (p < 0.05). Furthermore, the incidence of aberrations tended to increase in Dukes' B. Although translocation of chromosome 11 was also found in 17% of cases, it was not associated with histopathological features. Our findings indicate that the deletion of chromosome 11 is closely related to the progression of colorectal carcinoma.
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Aneusomy of chromosome 18 is associated with the development of colorectal carcinoma Reviewed
Nanashima A., Tagawa Y., Yasutake T., Sawai T., Tuji T., Sasano O., Nakagoe T., Ayabe H.
Journal of Gastroenterology 32 ( 4 ) 487 - 491 1997.8
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology
Specific loss of heterozygosity of chromosome 18 has been observed frequently in advanced colorectal carcinoma and is closely associated with its development. We investigated the prevalence of numerical aberrations of chromosome 18 in 44 specimens of colorectal carcinomas, using fluorescence in situ hybridization. We also examined the relationship between aneusomy of chromosome 18 and the clinicopathological features of these tumors. Aneusomy of the specimens (monosomy and polysomy) was determined when the same aneusomic population was detected in more than 15% of the nuclei. The frequency of monosomy and polysomy of chromosome 18 in colorectal carcinomas was 43% (19/44) and 29% (12/44), respectively. The prevalence of monosomy and polysomy 18 was significantly higher in cancers with invasion exceeding category T2 compared with T1 (P < 0.01), and with tumor size exceeding 20 mm in diameter compared with tumors less than 20 mm (P < 0.05). However, the prevalence of aneusomy 18 was not associated with other clinico-pathological features. The mean survival period and the 5-year survival rate after operation in patients with aneusomy 18 was not different from findings for those with disomy 18. Our results indicate that aneusomy of chromosome 18 is associated with the development of colorectal carcinoma; however, it is not a useful indicator of postoperative prognosis.
DOI： 10.1007/BF02934087
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Sawai T., Sasano O., Tsuji T., Nanashima A., Yasutake T., Kusano H., Tagawa Y., Nakagoe T., Ayabe H.
Japanese Journal of Gastroenterology 94 ( 7 ) 464 - 468 1997.7
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Gastroenterology
Numerical aberration of chromosome 17 of 14 cases of colorectal carcinoma with multiple primary cancer (multiple cancer) was compaired with that of 35 cases of colorectal carcinoma without any other cancer (single cancer). Fluorescence in situ hybridization with p17H8 was performed on touch smear from fresh materials. The proportion of aneusomy 17 (NCAI numerical chromosome aberration index) in multiple cancers was significantly higher than that of single cancers (37.7±10.5% VS 46.1±8.0% ;p < 0.01). Although NCAI of single cancers conformed to cancer progression (26.1±4.7% in Dukes A, 33.1±7.1% in Dukes B, 39.9±6.9% in Dukes C, and 45.7±12.0% in Dukes D), that of multiple cancers was high in all stages (44.7±7.3%, 44.4±6.8%, 50.4±11.2%, and 49.6±5.6%, respectively). Furthermore, the multiple numerical aberration of chromosome 17 in multiple cancers was more often than that of single cancers (64.3% VS 22.9% ;p < 0.01).
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Intragastric endoscopic surgery using the transanal endoscopic microsurgery technique
Nakagoe T., Sawai T., Uchikawa T., Nanashima A., Yamaguchi H., Yasutake T., Kusano H., Ayabe H.
British Journal of Surgery 84 ( 6 ) 1997.6
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：British Journal of Surgery
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Tagawa Y., Nanashima A., Yasutake T., Hatano K., Nishizawa-Takano J., Ayabe H.
Cytometry 27 ( 4 ) 327 - 335 1997.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cytometry
We studied differences in chromatin patterns and the spatial localization of centromeres of chromosome 11 during the cell cycle between normal peripheral blood lymphocytes (PBL) and human promyelocytic leukemia cells (HL-60) using fluorescence in situ hybridization. The pericentromeres in both cells were located at the periphery during Gq (quiescent) phase, but moved towards the nuclear center in G1 and mid-S phase. During G2, the pericentromeres of PBL continued to move towards the nuclear center whereas those of HL-60 returned to the periphery. The angle defining the spatial location of two pericentromeres, in reference to the center of the nucleus, increased in PBL cells from a mean of 67°during Gq phase to 106°during G1 phase (P < 0.01), and the two pericentromeres remained wide apart throughout the entire cell cycle. In HL-60, the angle also increased during G1, but then decreased during mid-S and G2 phases. Both cells exhibited pericentromeric signals during Gq that were round and compact, and the entire chromatin was loosely condensed. The signal became more loose and dispersed during the G1 and mid-S phases. The pericentromere signal varied during G2 and was generally rod-like or bipartite with condensation of the entire chromatin or chromosome-like. Our results suggest that subtle but important differences in spatial localization of pericentromeres are present during the interphase between normal PBL and HL-60 cells.
DOI： 10.1002/(SICI)1097-0320(19970401)27:4<327::AID-CYTO3>3.0.CO;2-9
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Cytogenetic analysis of gallbladder neoplasms using fluorescence in situ hybridization (FISH)
Nanashima A.
Journal of Hepato-Biliary-Pancreatic Surgery 4 ( 4 ) 431 - 435 1997.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Hepato-Biliary-Pancreatic Surgery
To characterize the numerical chromosome aberrations in gallbladder neoplasms, we examined surgically resected tissues using fluorescence in situ hybridization. The aberrations in 15 specimens of adenocarcinomas and 2 adenomas were compared with those in 4 samples of adenomyomatosis and 17 samples of normal epithelium. We calculated the frequency of aneusomy and determined the chromosome indexes (mean number of chromosomes per nucleus) of chromosomes 17 and 18. The pattern of DNA ploidy was analyzed by flow cytometry. In normal epithelium, adenomyomatosis and adenomas, DNA aneuploidy was not observed, while 13 (87%) carcinomas showed DNA aneuploidy, including 2 specimens with multiploidy. No numerical aberrations were observed in normal epithelium and adenomyomatosis. A numerical gain of chromosome 17 was observed in a single adenoma and in 10 (66%) carcinomas. A numerical gain of chromosome 18 was observed in 6 (40%) carcinomas, but not in other tissues. The chromosome index of chromosome 17 was significantly higher in adenomas and carcinomas (2.45 ± 0.60 and 2.29 ± 0.14, respectively) compared with normal epithelium. Our cytogenetic findings did not correlate with any histopathologic features of carcinomas. Our results indicated that the gains of chromosome 17 and 18 represented early chromosomal alterations in gallbladder neoplasms and were maintained in advanced carcinomas. © Springer-Verlag 1997.
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Nanashima A., Tagawa Y., Morinaga M., Kusano H., Nakagoe T., Ayabe H.
Journal of Gastroenterology 31 ( 6 ) 793 - 800 1996.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology
Quantitative analysis by fluorescence in situ hybridization (FISH) on thin paraffin-embedded tissue sections, using specific probes for chromosomes 11, 17, and 18 was employed in various morphological types of early and advanced colorectal cancer to clarify tumor cytogenetics. The chromosome index (CI) was calculated as a quantitative measure of the chromosome copy number. Compared with the CI of normal epithelium, the CI of chromosome 11 in villous components of adenomas or polypoid early cancers was decreased, while the CI in flat type or advanced colorectal cancers, conversely, was increased (P < 0.05). The CI of chromosome 17 in villous components of adenomas and all cancers was higher than that of normal epithelium (P < 0.05), but the differences were not significant. In protruding advanced cancers, the CI of chromosome 18 was significantly decreased (P < 0.01) compared to the CI of normal epithelium. There was no significant chromosomal heterogeneity between the superficial and the deepest layer in each cancer. In mucosa adjacent to sessile and flat type cancers, the CI of chromosome 17 was significantly higher than the CI in normal epithelium or adenomas (P < 0.05). These results suggest that numerical chromosome aberrations are associated with the histological type of adenoma and the morphological diversity of cancer in the colorectum, and that chromosome 17 abnormality occurs in mucosa adjacent to sessile and flat cancers.
DOI： 10.1007/BF02358604
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Nanashima A., Tagawa Y., Nakagoe T., Nishizawa-Takano J., Hatano K., Uchikawa T., Matsumoto Y., Taniguchi Y., Fujise N., Ayabe H.
Journal of Gastroenterology 31 ( 5 ) 646 - 653 1996.10
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology
The biological characteristics associated with the morphological diversity of colorectal cancers were investigated to elucidate the causes of this diversity. We examined the proliferative and infiltrating activity of tumor cells, indicated by the mean number of Ag nucleolar organizer region associated proteins (NORs) per nucleus (MNA) and the immunohistochemical response to cathepsin B(CB), in various morphological types of early and advanced colorectal cancers. We examined 73 colorectal cancers obtained by endoscopic and surgical resection. MNA values for sessile and flat-elevated cancers were greater than the values for pedunculate, subpedunculate, and flat-or-depressed early cancers (sessile, P < 0.05). In advanced cancers invading the muscularis propria, protruding cancers showed significantly higher MNA values than small ulcerative cancers (P < 0.01). CB expression increased significantly with the progression of colorectal cancers (P < 0.01), but was not related to morphological diversity in early and advanced cancers. In both sessile and flat cancers, CB expression was higher in moderately differentiated than in well differentiated adenocarcinomas. These results indicate that, in colorectal cancers, protruding early cancers without stalks and protruding advanced cancers have higher proliferative activity than pedunculate or flat early cancers and small ulcerative advanced cancers, respectively, and that CB expression is not associated with morphological diversity, but with depth of invasion and histological differentiation.
DOI： 10.1007/BF02347611
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A case of advanced colon cancer measuring 8 mm in diameter
Sawai T., Sasano O., Tsuji T., Nakamura S., Nanashima A., Uchikawa T., Yamaguchi H., Yasutake T., Kusano H., Tagawa Y., Nakagoe T., Ayabe H., Fukuda Y.
Journal of the Japan Society of Colo-Proctology 49 ( 4 ) 323 - 326 1996
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of the Japan Society of Colo-Proctology
A 68 year-old male who had underwent sigmoidectomy for colon cancer on April 6, 1992 was admitted to our hospital. Colonoscopy revealed a small flat-elevated lesion with converging folds of the ascending colon. On preoperative evaluation of a massive invasion to the submucosal layer, right hemicolectomy was performed on September 8, 1994. Macroscopic examination of the resected specimen showed a slightly elevated tumor with converging folds, measuring 5 x 8 mm in diameter. Histopathology revealed a well differentiated adenocarcinoma invading to the subserosal layer. No residual adenomatous tissue was identified, and no metastasis was found in 14 lymph nodes. The proliferating activity of thin small advanced colon cancer was determined by double staining technique of Ki-67 and argyrophilic nucleolar organizer resions (AgNOR) using formalin-fixed paraffin-embedded sections. Labeling index of Ki-67 monoclonal antibody (MIB 1) was 7.3 %. Although the Ki-67 negative cells had low AgNOR counts (mean 2.50), the Ki-67 positive cells had high AgNOR counts (mean 9.98 per nucleus).
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Sawai T., Tagawa Y., Nakagoe T., Yasutake T., Uchikawa T., Nanashima A., Morinaga M., Yamaguchi H., Kusano H., Ayabe H., Tomita M., Miura T.
GASTROENTEROLOGICAL ENDOSCOPY 37 ( 8 ) 1593 - 1599 1995
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：GASTROENTEROLOGICAL ENDOSCOPY
Numerical aberrations of chromosomes # 11 and #17 were evaluated in 22 colorectal carcinomas using endoscopic biopsy specimens by fluorescence in situ hybridization (FISH) with repetitive satellite DNA probes. The patients who were admitted to our hospital for surgical treatment included 7 women and 15 men. The mean age of onset was 67.6 years old (range, 33 to 83). FISH revealed numerical aberrations in 10 out of 20 (50%) on chromosome 11, and 15 out of 22 (68%) on chromosome 17. There were monosomy 11 in 3, trisomy 11 in 7, monosomy 17 in 1, trisomy 17 in 10, and tetrasomy 17 in 4. Although there was no particular relationship between the numerical chromosome instability of #11 and clinicopathologic parameters of colorectal carcinomas, that of #17 was significantly higher in patients with lymph node metastasis (34.0±8.2%VS42.0±10.3%, p<0.05). These results suggested that numerical chromosome instability of #17 may be a marker of lymph node metastasis of colorectal carcinomas, and FISH using endoscopic biopsy specimens was a useful technique for preoperative detection of numerical chromosome aberrations. © 1995, Japan Gastroenterological Endoscopy Society. All rights reserved.