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G Sakamoto

Publications and source records attributed to G Sakamoto.

At least 55 records · Page 3Linked to original sources
PubMed1999

Monitoring of interobserver agreement in nuclear atypia scoring of node-negative breast carcinomas judged at individual collaborating hospitals in the National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) protocol.

BACKGROUND: In the NSAS-BC protocol, the nuclear atypia and mitotic counts are to be judged by pathologists at each participating hospital for assessing high-risk node-negative breast cancers. Therefore, maintenance of interobserver agreement in diagnosis at a higher level is mandatory during the period of patient entry. METHODS: Individual collaborating pathologists originally evaluated the histological eligibility of 107 cases. Three panel pathologists determined consensus diagnoses and 29-37 collaborating pathologists determined modal diagnoses of these cases at three slide conference sessions. The original diagnoses were compared with the consensus and modal diagnoses to estimate the percentage of erroneous judgments. RESULTS: The agreement rate in histological type and nuclear atypia score was 69% (74/107) between the original and consensus diagnoses, 76% (81/107) between the original and modal diagnoses and 86% (92/107) between the consensus and modal diagnoses. The strength of interobserver agreement at the slide conference sessions was moderate (0.447-0.535) by kappa statistics. The original, consensus and modal diagnoses were concordant in 71 cases (66%), but were discordant in 36. Of 35 invasive ductal carcinomas with discordant diagnoses, the discordance arose from the intermediate tumor nature in 15, multiple factors in 13 and erroneous diagnosis in seven (6.5%), if the characteristics of the tumor were judged from the percentage interobserver agreement per tumor at the slide conferences. CONCLUSION: Nuclear atypia scoring given at individual hospitals on case entry was almost reproducible among the pathologists. Continuous efforts are needed to improve interobserver agreement and to decrease erroneous diagnosis for protocol eligibility.

Breast Neoplasms↗
PubMed1999

Allelic loss at 1p34, 13q12, 17p13.3, and 17q21.1 correlates with poor postoperative prognosis in breast cancer.

Allelic losses of tumor suppressor genes (TSGs), or the chromosomal regions harboring them, in tumor DNA may become useful postoperative prognostic indicators. To examine whether specific allelic losses might correlate with postoperative survival in a 5-year prospective follow-up, we tested tumors from a cohort of 264 breast cancer patients for allelic losses of 18 microsatellite markers representing either a known TSG or a region where genetic alterations are frequent in breast tumors. Patients whose tumors had lost an allele at 1p34, 13q12, 17p13.3, or 17q21.1 had significantly higher risks of postoperative mortality than those whose tumors retained both alleles at those loci (at 1p34, a 5-year mortality rate of 29% among patients with losses vs. 7% with retentions, P = 0. 0008; at 13q12, 31% vs. 10%, P = 0.0062; at 17p13.3, 24% vs. 13%, P = 0.026; and at 17q21.1, 31% vs. 13%, P = 0.0047). Furthermore, combined losses at 13q12 and 17p13.3 increased the predicted postoperative mortality risks by a factor of 9.6 (5-year mortality rate of 42% vs. 5% with retentions, P = 0.0001), and combined losses at 1p34 and 17p13.3 raised the predicted postoperative mortality risks by a factor of 8.6 (27% vs. 3%, P = 0.0064). We conclude that allelic losses at these loci can serve as negative prognostic indicators to guide postoperative management of patients. Genes Chromosomes Cancer 26:134-141, 1999.

Adult↗
PubMed1998

Frequent Allelic Loss at 6q26-27 in Breast Carcinomas of the Solid-tubular Histologic Type.

To characterize the effect that inactivation of a putative tumor suppressor gene on 6q appears to have on breast carcinogenesis, we examined loss of heterozygosity in 528 primary breast carcinomas with a polymorphic marker located at 6q26-27, a frequent target region of allelic loss in ovarian and breast cancers. Ofthe 56 informative tumors of the solid-tubular type, 29(52&precnt;)showed allelic lossat 6q26-27;however, only 10 of 42 papillotubular carcinomas(23%)and 34 of 86 scirrhous carcinomas(39%)showed allelic loss(p = 0.0215). These results are consistent with reported alterations at 6q26-27 in serous and mucinous types of ovariancancers, in that they suggest that inactivation of one or more genes in that region may affect carcinogenic mechanisms in a histologic type-specific manner in neoplasms of the female reproductive organs.

Journal Article↗
PubMed1998

Allelic loss on chromosome 1p is associated with progression and lymph node metastasis of primary breast carcinoma.

BACKGROUND: Frequent allelic losses on the short arm of chromosome 1 have been observed in a wide variety of human tumors. Cytogenetic and molecular genetic studies in breast carcinomas have shown frequent alterations on chromosome 1, involving loss of 1p or gain of 1q. METHODS: To define the locations of tumor suppressor genes, 143 primary breast carcinomas were examined for allelic loss using 15 highly polymorphic microsatellite markers on 1p. Correlations also were sought between allelic loss on 1p and several clinicopathologic parameters. RESULTS: Allelic loss was observed in 73 of the tumors (51%). Detailed deletion mapping identified target regions at 1p36, 1p34-p35, and 1p22-p31. Allelic losses at 1.36 or 1p34-p35 were observed more frequently in tumors of the solid tubular and scirrhous types than in less aggressive histologic types. Conversely, allelic loss at 1p22-p31 was correlated with lymph node metastasis and a tumor size > 2 cm. CONCLUSIONS: Inactivation of tumor suppressor genes that lie in either 1p36 or 1p34-p35 might affect carcinogenic mechanisms in a histologic type specific manner, especially the solid tubular and scirrhous types. Alterations of one or more tumor suppressor genes at 1p22-p31 may play a role at late stages of breast carcinogenesis, especially with regard to local progression and lymph node metastasis.

Adenocarcinoma↗
PubMed1998

Identification of a new commonly deleted region within a 2-cM interval of chromosome 11p11 in breast cancers.

Allelic loss has been observed on the short arm of chromosome 11 in a variety of human cancers. We have examined 184 breast cancers for allelic loss anywhere in chromosome 11p, using 15 well-spaced microsatellite markers. Allelic loss was observed in 86 cases (47%) and a new commonly deleted region 2-cM in length was identified at 11p11 between loci D11S986 and D11S1313, in addition to a 12-cM region of a common deletion at 11p15.5. A significant association was found between allelic loss on 11p15.5 and LOH on 11p11 and the loss of progesterone receptors.

Autoradiography↗
PubMed1998

Establishment of histological criteria for high-risk node-negative breast carcinoma for a multi-institutional randomized clinical trial of adjuvant therapy. Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) Pathology Section.

BACKGROUND: A multi-institutional randomized clinical trial of adjuvant therapy for patients with high-risk node-negative (n0) breast cancer has been undertaken in Japan. The pathology panel was organized in order to establish histological criteria to identify patient groups with higher rates of recurrence. METHODS: Initially, three pathologists independently judged the nuclear grade, composed of nuclear atypia and mitotic counts, of 100 n0 invasive ductal carcinomas, focusing on interobserver variation of the nuclear grade and its correlation with patient prognosis. These pathologists then gave consensus histological types and nuclear grades for 130 other n0 breast carcinomas and examined the prognostic significance of the grade. RESULTS: In the first study, nuclear grade 2-3 significantly identified a patient group with a rate of recurrence of 17-20% by any pathologists and the degree of agreement for the grade was fair. In the second study, the consensus type and nuclear grade identified a group (n = 66) with a 22% recurrence rate and another group (n = 64) with a 3.6% recurrence rate at 10 years. In 12 tumors, the resection-fixation interval of the tumor did not generate any significant difference in mitotic counts. CONCLUSIONS: The histological type and the nuclear grade clearly identified a higher-risk patient group with n0 breast carcinoma, and may be applied to the multi-institutional protocol study when the criteria have been well standardized by the pathologists.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Allelic loss on chromosome 9q is associated with lymph node metastasis of primary breast cancer.

Frequent allelic losses on chromosome 9 are seen in a wide variety of human tumors; moreover, two genes (P16 and PTC) whose mutant alleles confer predispositions to some inherited cancer syndromes have been identified on this chromosome. Using 15 highly polymorphic microsatellite markers distributed on both arms of chromosome 9, we tested 96 primary breast carcinomas for allelic loss in order to define the locations of genes that might be involved in this type of tumor. Allelic loss was observed in 37 of the tumors (39%) and detailed deletion mapping identified target regions at 9p21, 9q22.3 and 9q33. Losses at 9q22.3 and 9q33 were correlated with the presence of lymph node metastasis, and allelic loss at 9q22.3 was observed more frequently in scirrhous tumors than in less aggressive histologic types. Therefore, inactivation of tumor suppressor genes in 9q22.3 and 9q33 regions might play a role in progression of breast cancers, especially in metastasis to lymph nodes and in development of scirrhous tumors.

Adenocarcinoma, Scirrhous↗
PubMed1998

Frequent allelic loss at 7p14-15 associated with aggressive histologic types of breast cancer.

We examined 142 primary human breast cancers to determine their patterns of loss of heterozygosity (LOH) at 19 microsatellite markers over the entire length of chromosome 7. Allelic loss at one or more loci on the short arm of chromosome 7 was observed in 37 of the tumors (26%). We found a new target region of allelic loss on 7p between D7S1802 and D7S817 at 7p14-15. LOH on 7p was found more frequently in tumors of the invasive solid tubular and scirrhous type (31 of 87); 36%) than in other less aggressive types (2 of 27; 7%) (P = 0.0047). The results suggest that inactivation of putative tumor suppressor gene(s) located at 7p14-15 may play a role in the development and/or progression of primary breast cancers, particularly those of the invasive solid tubular and scirrhous type. Allelic loss was also found in 56 of 142 tumors on the long arm, and a commonly deleted region was defined between D7S522 and D7S1801 at 7q31.

Breast Neoplasms↗
PubMed1998

Mapping of a new target region of allelic loss to a 2-cM interval at 22q13.1 in primary breast cancer.

Allelic losses on chromosome arm 22q are frequently observed in human meningiomas and in carcinomas of the colon, ovary, and breast. Among 140 primary breast cancers we examined for loss of heterozygosity (LOH) at 16 polymorphic loci on the long arm of chromosome 22, 56 (40%) showed LOH for at least one locus. Eleven of these tumors had retained heterozygosity for markers proximal to the NF2 locus but showed LOH for markers distal to NF2. Deletion mapping indicated a new common region of deletion, 2-cM in extent, at q13.1 between Interleukin 2 receptor beta (IL2RB) and D22S279. Our results raise the possibility that one or more tumor suppressor genes associated with breast cancer may exist at 22q13.1. Comparison of these results with clinicohistological data indicated that allelic losses on 22q tend to occur more frequently in tumors of malignant histological types.

Alleles↗
PubMed1998

[Relationship between DNA ploidy and survival in breast cancer].

The DNA ploidy pattern from fresh frozen specimens and survival rate was investigated in 91 primary breast cancers. Diploid patterns were found in 32 (35.2%) and aneuploid patterns in 59 (64.8%). The 5-year overall survival rate was significantly lower in aneuploid cases (76.3%) than diploid cases (93.8%) (p = 0.042), while there was no significant difference in disease-free survival between the two groups. there were negative nodes, no significant differences in 5-year overall or disease-free survival between patients with diploidy and aneuploidy. In contrast, when there were positive nodes, the 5-year overall and disease-free survival rates in patients with aneuploidy were 60.6% and 48.5%, which were significantly lower (p = 0.048 and p = 0.030) than the corresponding percentages of 92.3% and 84.6%, in those with diploidy. When the ploidy pattern was compared with other factors, a very close correlation was found between the ploidy pattern and histological grading (p < 0.0001). The ploidy pattern determined by flow cytometric DNA analysis may reflect the grade of malignancy of the breast cancer.

Breast Neoplasms↗
PubMed1998

Mapping of a new target region of allelic loss to a 6-cM interval at 21q21 in primary breast cancers.

A detailed analysis of loss of heterozygosity (LOH) in breast cancers was performed with 11 microsatellite markers on the long arm of chromosome 21. Among the 142 tumors examined, 44 (31%) showed LOH at one or more loci. Peak LOH frequency was observed on band 21q21. Deletion mapping identified a new commonly deleted region in a 6-cM interval of 21q21 between loci D21S1432 and D21S1437, and raised the possibility that one or more tumor suppressor genes associated with breast cancer may exist in this region. Comparison of these alterations with clinicopathological parameters revealed an association of LOH on 21q with loss of progesterone receptor (P = 0.0013).

Breast Neoplasms↗
PubMed1997

Correlation of Allelic Losses and Clinicopathological Factors in Primary Breast Cancers.

Human breast cancers frequently show allelic loss or loss of heterozygosity (LOH) at apecific chromosomal regions. To understand the possible role of these genetic alterations in tumor development and progression, we examined LOH at loci on chromosomal arms 1p, 3p. 11p, 13q, 16q, 18q, and 22q in 140 to 246 cases of primary breast cancers and compared it with lymph node metastasis, histological type, tumor stage, estrogen receptor (ER) and progesterone receptor (PgR) status. LOH at 1p22-31 correlated with lymph node metastasis and a tumor size of greater than 2 cm. LOH at 13q12-14 and 18q21 were most frequently observed in tumors of the solid-tubular type. LOH at 1p34-36 was more frequent in tumors of the scirrhous and solid-tubular types than in other less aggressive histological types. Furthermore, a significant association was observed between LOH at 3p14-21, 11p11-15 and 13q12-14 and the absence of progesterone receptors. These results suggest that some clinical characteristics of breast cancers are determined by loss of tumor supperssor genes present at specific chromosomal regions.

Journal Article↗
PubMed1997

Mapping of a breast cancer tumor suppressor gene locus to a 4-cM interval on chromosome 18q21.

DPC4 and DCC, putative tumor suppressor genes implicated in the genesis of several types of human cancer, lie on the long arm of human chromosome 18. We examined 200 primary breast cancers for allelic losses on chromosome 18, using 15 microsatellite markers distributed along the long arm. Allelic loss was detected most frequently (29-30%) at loci mapped to 18q21. Deletion mapping of the 34 tumors showing partial or interstitial deletions identified a commonly deleted region within the 4-cM interval flanked by D18S474 and D18S487 at 18q21.1-q21.3. Although this interval included the DPC4 and DCC genes, we excluded DPC4 from candidacy when polymerase chain reaction-single-strand conformation polymorphism analysis of each exon failed to detect abnormalities in any of the 54 breast cancers that exhibited loss of heterozygosity involving 18q. Allelic loss on 18q was found more frequently in tumors of the solid tubular histological type (24 of 55, 44%) than in other types (24 of 113, 21%) (P = 0.0049). The results suggest that a tumor suppressor gene located within the 4-cM region at 18q21, either DCC or another gene not yet identified, may play a role in the development of some sporadic breast cancers, particularly those of the solid tubular type.

Alleles↗
PubMed1997

Detailed deletion mapping of chromosome arm 3p in breast cancers: a 2-cM region on 3p14.3-21.1 and a 5-cM region on 3p24.3-25.1 commonly deleted in tumors.

Loss of heterozygosity (LOH) on 3p is frequent in human renal cell carcinomas, lung cancers, and breast cancers. To define the region(s) on 3p that harbor presumptive tumor suppressor gene(s) for breast cancer, we examined 196 primary breast tumors for their patterns of LOH at 22 microsatellite marker loci distributed along this chromosome arm. Allelic loss at one or more loci was observed in 101 (52%) of these tumors. Detailed deletion mapping identified two distinct commonly deleted regions; one was localized to a 2-cM interval flanked by D3S1547 and D3S1295 at 3p14.3-21.1, and the other to a 5-cM interval flanked by D3S1286 and D3S1585 at 3p24.3-25.1. The FHIT gene lies in the vicinity of the proximal commonly deleted region. Attempts to correlate LOH on 3p to clinicopathological parameters detected an association with the absence of the progesterone receptor (P = 0.0096). The results suggest that inactivation of unidentified tumor suppressor genes on 3p plays a role in the mechanism whereby hormone dependency is lost in the course of breast carcinogenesis.

Breast Neoplasms↗
PubMed1995

Experience of quadrantectomy with axillary dissection without radiotherapy sustained by serial pathological examination for stage I breast cancer.

Breast conserving treatment usually consists of lumpectomy and axillary dissection followed by a limited dose of irradiation so that no significant side-effects occur. However, the precision of lumpectomy depends on the surgical maneuver and pathological evaluation performed at each institution. For this reason, post-operative irradiation to the preserved breast and for the occult carcinoma in the same breast is absolutely mandatory, and effectively becomes a routine step. In 1986, we started to adopt the new breast-conservation method of quadranectomy with axillary dissection for restricted stage I breast cancer without using radiotherapy, at the Cancer Institute Hospital, Tokyo, Japan. As an alternative to irradiation to ensure safety, we chose to administer an elaborate pathological examination on serial sections. The pathological proof has saved troublesome post-operative irradiation, and the results have shown this method to be safe and clear-cut compared to the traditional breast-conserving treatment cited in the literature. From July 1986 to December 1994, we performed 321 cases of quadranectomy and axillary dissection (Q+Ax). If the detailed pathological examination of 5-mm serial sections revealed the stump to be negative, we did not treat the preserved breast with radiotherapy. Out of 321 cases, 247 were analyzed as being stump-negative and of these 235 did not receive radiotherapy at all. During a 5 year 4 month observation period, we have not yet encountered any local recurrence. However, we have experienced 4 cases (1.70%) in which a second cancer developed in the conserved breast. The annual incidence rate was 0.32%. These results are the best so far compared to other published world reports.

Aged↗
PubMed1995

Incidence of latent breast cancer in Japanese women.

Detection of small or early neoplastic lesions is essential for the secondary prevention of cancer, and for this purpose information concerning their incidence and characteristics is required. Although data for latent or early cancers are available for various organs, details are limited in the case of the breast. The present investigation was carried out to cast light on the incidence of latent cancers, considered as lesions, in women with no symptoms and no palpable mass of the breast. Out of 2126 women visiting our hospital for initial breast examination during July to December in 1987, 542 (25.5%) had no complaint and neither a detectable mass on careful palpation nor a tumor shadow on mammography. However, 21 (3.9%) demonstrated microcalcification, 7 giving the impression of a possible malignancy. Subsequent biopsy of the 7 cases revealed 3 carcinomas. The detection rate of breast cancer in this population was thus 0.6% (3/542). Adopting the frequency (36%) of microcalcification detectable on mammography in 185 breast cancers diagnosed in this period as a base, the incidence of latent breast cancer among women visiting our hospital was calculated to be 1.5%.

Adult↗