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F Kasumi

Publications and source records attributed to F Kasumi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Allelic loss at the 8p22 region as a prognostic factor in large and estrogen receptor negative breast carcinomas.

BACKGROUND: Allelic losses of tumor suppressor genes, or the chromosomal regions harboring them, in the DNA of tumor cells may become useful postoperative prognostic indicators. The authors studied frequent loss of heterozygosity (LOH) on chromosome 8p22 and its association with disease progression that occurred later in patients with breast carcinoma. METHODS: To examine whether allelic losses at 8p22 might correlate with postoperative survival during a 5-year period of prospective follow-up, the authors tested tumors from a cohort of 298 breast carcinoma patients informative for 8p22 markers. The tumors were tested for allelic losses of microsatellite markers D8S136 and D8S1106 located at 8p22, a chromosomal region where genetic alterations are frequent in breast carcinomas. RESULTS: Among the 298 breast carcinoma patients, 154 (52%) lost alleles in tumors. Patients whose tumors had lost an allele at 8p22 had a significantly higher risk of postoperative mortality than those whose tumors retained both alleles at those loci; their 5-year mortality rates were 18% (26 patients died among 154 with losses at 8p22) versus 7% (10 patients died among 144 with retentions at 8p22) (P = 0.017). The 8p22 LOH was a significant independent prognostic factor for postoperative survival in a group of patients with large tumors (>2.1 cm) and in a group of patients with estrogen receptor negative tumors in both univariate and multivariate analyses. These data show that 8p22 LOH was a significant prognostic factor for the postoperative survival of certain clinical groups of patients who underwent surgery for breast carcinoma. CONCLUSIONS: Allelic loss on chromosome 8p22 can serve as a negative prognostic indicator to guide the postoperative management of patients, especially patients with large tumors (>2.1 cm) and those with estrogen receptor negative tumors.

Adult↗
PubMed2000

Surgery for ductal carcinoma in situ.

BACKGROUND: Ductal carcinomas in situ (DCIS) are sometimes treated too aggressively by surgery. We discuss minimal invasive surgery for DCIS on the basis of our experience at the Cancer Institute Hospital in Tokyo. METHODS: We performed surgery for 667 cases of DCIS between 1987 to 1998. This twelve year period we divided into three periods; 1987-1990,1991-1994, and 1995-1998. RESULTS: DCIS comprised 10% of all breast cancers, and tended to increase in incidence over time. The number of minimally invasive procedures such as breast conserving treatment (BCT), surgery without axillary dissection, and day surgery increased in later periods. In BCT for DCIS the surgical margin status is the most important factor, the rate of negative surgical margins was higher in DCIS than invasive cancer, and especially high in cases of mammographically detected nonpalpable cancer, the incidence of which is increasing yearly. The outcome of the 667 cases was very good. No distant metastases were observed, and the incidence of ipsilateral breast cancer(including second primary cancer) in these cases was 5% CONCLUSIONS: Because small cancers, including nonpalpable cases, will be detected more frequently, minimal invasive surgery will become more common for DCIS.

Axilla↗
PubMed2000

Mammographic and clinicopathological features of mucinous carcinoma of the breast.

BACKGROUND: We attempted to improve the effectiveness of diagnostic techniques in mammographic imaging of mucinous carcinoma of the breast by defining the characteristics of mammographic images and investigating correlations between these images and various clinicopathological findings. METHODS: Clinicopathological investigations of 92 lesions in 90 cases of mucinous carcinoma of the breast were made. Mammography demonstrated 80 lesions with identical tumor shadow characteristics and these were divided into three patterns, circumscribed, indistinct and blended. Correlations between clinicopathological findings and mammographic images were investigated. RESULTS: Patients with mucinous carcinoma of the breast usually present with a palpable mass. The lymph node metastasis rate in this study was low and prognosis in the early postoperative period was satisfactory. On mammograms, the circumscribed pattern was the most frequent. The investigation of the correlation between histological sub-type and mammographic pattern showed a high percentage of pure type lesions exhibited in the circumscribed pattern while those of mixed histologic type often showed the indistinct pattern. Calcification frequency demonstrated on mammography was 75% for the indistinct and mixed patterns, and approximately 50% for the circumscribed pattern. A high rate of calcification seen outside the tumor shadow suggested a high frequency of invasion and the spread of cancer to neighboring tissues. The circumscribed pattern was least frequently associated with lymph node metastasis, followed by the indistinct and blended patterns in that order. CONCLUSION: Investigation of clinicopathological factors and mammographic findings in mucinous carcinoma of the breast suggests that mammography provides clinically valuable information for the treatment of this disease. These findings indicate the importance of careful mammographic observation at the time of diagnosis.

Adenocarcinoma, Mucinous↗
PubMed2000

Identification of Rad51 alteration in patients with bilateral breast cancer.

The human Rad51 gene, HsRAD51, is a homolog of RecA of Escherichia coli and functions in recombination and DNA repair. BRCA1 and BRCA2 proteins form a complex with Rad51, and these genes are thought to participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Additionally, we have shown that the pattern of northern blot analysis of the RadS gene is closely similar to those of the BRCA1 and BRCA2 genes. It is therefore possible that alterations of the Rad51 gene may be involved in the development of hereditary breast cancer. To investigate this possibility, we screened Japanese patients with hereditary breast cancer for Rad51 mutations and found a single alteration in exon 6. This was determined to be present in the germline in two patients with bilateral breast cancer, one with synchronous bilateral breast cancer and the other with synchronous bilateral multiple breast cancer. In both patients, blood DNAs showed a G-to-A transition in the second nucleotide of codon 150, which results in the substitution of glutamine for arginine. As this alteration was not present in any patients with breast or colon cancer examined, we assume that this missense alteration is likely to be a disease-causing mutation.

Blotting, Northern↗
PubMed2000

Surgical treatment of hepatic metastases from breast cancer.

We have performed a retrospective study to evaluate whether surgical treatment is beneficial in patients with hepatic metastases from breast cancer. Between September 1985 and September 1998, 25 patients with hepatic metastases (14 solitary and 11 multiple), eight of whom had extrahepatic metastases, underwent hepatectomy. All of the detectable liver metastasis were resected in all of the cases. There were no severe postoperative complications. All but one of the patients received adjunctive polychemotherapy after the hepatectomy. After the hepatectomy, recurrent tumors were detected in 18 of the patients, being located in the liver in 12 (67%) of them. Overall, however, hepatectomy ensured that the liver was clinically recurrence-free for a median of 24 months (range 2-132 months). Eleven patients died of recurrent tumors, two died of other causes and the remaining 12 are currently alive. The 2- and 5-year cumulative survival rates after hepatectomy were 71% and 27%, respectively, and the median survival duration was 34.3 +/- 3.2 months, much better than the period of 8.5 months for another series of patients treated with standard or non-surgical therapies at our institution. The number and the size of hepatic metastases, the interval between treatment of the primary lesion and hepatectomy, and the existence of extrahepatic metastasis were not adverse prognostic factors. In conclusion, our data, although limited and highly selective, suggest that surgical treatment of hepatic metastases from breast cancer may prolong survival in certain subgroups of patients to a greater extent than standard or non-surgical therapies.

Adult↗
PubMed2000

Mapping of target regions of allelic loss in primary breast cancers to 1-cM intervals on genomic contigs at 6q21 and 6q25.3.

Allelic losses on the long arm of human chromosome 6 are frequently observed in cancers of the ovary, prostate, and breast. To identify the locations of putative tumor suppressor genes on 6q, we examined 192 primary breast cancers for patterns of allelic loss at 16 polymorphic microsatellite loci distributed along this chromosome arm. Allelic losses at one or more loci were observed in 105 (55%) of the tumors examined. Detailed deletion mapping with appropriate yeast artificial chromosome (YAC) contigs identified two distinct commonly deleted regions; one was confined to a 1-cM interval at 6q21 flanked by D6S1040 and D6S262 and the other to a 1-cM interval at 6q25.3 flanked by D6S305 and D6S411. Allelic losses at 6q21 were more frequent in invasive solid tubular and scirrhous carcinomas than in tumors of less aggressive histologic types (P = 0.0006). Allelic loss at 6q25.3 was associated with loss of progesterone receptor (P = 0.0256). Our results suggest the presence of two tumor suppressor genes for breast cancer on 6q that are likely to be associated with tumor progression and / or loss of hormonal dependency.

Adenocarcinoma↗
PubMed2000

[Characteristics of familial breast cancer].

We report the clinical characteristics of familial breast cancer families at our hospital in which the number of second-degree of breast cancer probands was more than 2. In our hospital, the incidence of onset at a young age was 21.9%, and bilateral breast cancer was 10.5%. These incident rates were significantly higher than sporadic breast cancer. The frequency of familial breast cancer in most Japanese hospitals was about 1.1%, but was 2.0% in our hospital. Familial breast cancer is a rare breast cancer, but the risk is high in breast cancer families. Therefore, it is necessary to follow up not only patients but the families.

Age Factors↗
PubMed2000

Allelic loss at 1p34-36 predicts poor prognosis in node-negative breast cancer.

Allelic losses of specific chromosomal regions in the DNA of tumor cells, which imply loss of tumor suppressor genes normally resident at those loci, may become useful postoperative prognostic indicators for breast cancers that have not yet metastasized to lymph nodes. To examine whether specific allelic losses might correlate with postoperative disease-free survival, we tested tumors from a cohort of 228 node-negative breast cancer patients for allelic losses at 18 microsatellite loci chosen to represent either a known tumor suppressor gene or a region where genetic alterations are frequent in breast tumors. We followed the patients clinically for 5 years or until death (if patient death occurred before completion of 5 years of follow-up). Patients whose tumors had lost an allele at 1p34-36 bore significantly higher risks of postoperative recurrence than those whose tumors retained both alleles of the markers in that region [the 5-year recurrence rate was 15% among patients with losses versus 2% among patients with retention (P = 0.001)]. Multivariate analysis demonstrated that allelic loss at 1p34-36 was an independent postoperative predictor of shorter disease-free survival (hazard ratio, 5.8; P = 0.0117). Thus, allelic losses at 1p34-36 in a tumor might have a potential to serve as a negative prognostic indicator to guide postoperative management of breast cancer patients, especially in the selection of high-risk women who will benefit from adjuvant chemotherapy and endocrine therapy.

Adult↗
PubMed2000

[Day surgery for breast cancer].

In Japan, day surgery for breast cancer usually means partial mastectomy without axillary dissection for small carcinoma under local anesthesia in the outpatient clinic. If histopathological examination of the specimens by serial section reveals that the cancer is noninvasive and completely resected with negative surgical margins, no additional surgery under general anesthesia is needed, and the patient does not require hospitalization. We call this procedure "probe lumpectomy". From 1991 to 1998, 169 patients underwent probe lumpectomy in our institution, and there were no major complications. Of these 169 patients, 64 did not require hospitalization. Ipsilateral breast cancer was observed in two patients, and these tumors were diagnosed not as recurrence but as second primary cancers. No distant metastases were observed. As sentinel node biopsy, which is not always easy under local anesthesia, becomes more common, the indications for day surgery or short-stay surgery will expand. As breast cancer is a malignant disease, informed consent and careful follow-up are needed if the treatment is completed only in the outpatient clinic.

Ambulatory Surgical Procedures↗
PubMed1999

Correlation of Allelic Loss with Poor Postoperative Survival in Breast Cancer.

BACKGROUND: Allelic losses of tumor suppressor genes or the chromosomal regions harboring them in the DNA of tumor cells may become useful postoperative prognostic indicators. METHODS: To examine whether specific allelic losses correlate with postoperative survival in a five-year prospective follow-up, we tested tumors from a cohort of 504 breast cancer patients for allelic loss of 18 microsatellite markers representing either known tumor suppressor genes or regions where genetic alterations are frequent in breast tumors. RESULTS: Patients with allelic loss at 1p34, 3p25, 8p22, 13q12, 17p13.3, or 17q21.1 had a significantly higher risks of postoperative mortality compared withthose whose tumors retained both alleles at those loci (at 1p34, the 5-year mortality rate was 23% among patients with loss vs 10% with retention, p 0.0100; at 3p25, 22% vs 9%, p =0.0014; at 8p22, 24% vs 7%, p =0.0177; at 13q12, 19%vs 8%, p=0.0093; at 17p13.3, 19% vs 9%, p=0.0078; and at 17q21.1, 17% vs 10%, p =0.0475). CONCLUSION: Allelic losses at these loci can serve as negative prognostic indicators to guide post-operative management, especially in the selection of thosewho will benefit from intensive adjuvant therapies.

Journal Article↗
PubMed1999

Somatic mutation of the PTEN/MMAC1 gene in breast cancers with microsatellite instability.

The extent to which microsatellite instability (MI) contributes to the etiology of breast cancer has not been established in any large-scale studies. We examined 528 samples of tumor DNA from patients with primary breast cancer for MI, using 14 polymorphic CA-repeat markers. The frequency of MI in these tumors was unexpectedly low (10/528, 1.9%). The ten MI+ tumors were analyzed for mutations in five potential target genes that contain simple repeat sequences (TGFBIIR, IGF2R, hMSH6, BAX and PTEN/MMAC1). A somatic insertion of an extra adenine in the (A)6 region at codon 321-323 (exon 8) of the PTEN/MMAC1 gene, leading to a frame-shift, was identified in one tumor. This observation represented the first documented instance of PTEN/MMAC1 alteration in a MI+ primary breast cancer.

Breast Neoplasms↗
PubMed1999

Frequent multiplication of chromosome 1q in non-invasive and papillotubular carcinoma of the breast.

Carcinogenesis is considered to be a multistep process that may involve cumulative genetic alterations; one of these mechanisms, gain of chromosomal material, has the potential to activate tumor-promoting genes in breast carcinogenesis. Using 12 polymorphic microsatellite markers on the long arm of chromosome 1 (1q), we examined 130 sporadic breast carcinomas for abnormalities in the copy numbers of these loci in tumor cells using a differential PCR method. We also sought correlations between alterations on 1q and several clinicopathological parameters. At every locus examined, a 2-3-fold increase in copy number of an allele in tumor material was observed in one third of the tumors (46 of 130, 35%), indicating 'multiplication' of 1q. This multiplication involved the entire long arm in majority of those tumors (43 cases, 93%). The multiplication of 1q was observed more frequently in non-invasive ductal and papillotubular histological types than in solid-tubular and scirrhous types (13/25, 52% vs. 27/90, 30%) (P = 0.041). The predominant chromosomal alterations on 1q in breast carcinomas are found to be multiplications rather than losses. The multiplication represents polysomy of the entire region of 1q, and may confer a growth advantage during development and/or progression of non-invasive ductal and papillotubular histologic types of breast carcinomas.

Adenocarcinoma, Papillary↗
PubMed1999

Frequent multiplication of chromosomal region 8q24.1 associated with aggressive histologic types of breast cancers.

Carcinogenesis is considered to be a multi-step process that may involve cumulative genetic alterations. One such alteration, gain of chromosomal material, has the potential for activating genes that promote carcinogenesis in breast tissues. Using 14 polymorphic microsatellite markers on the long arm of chromosome 8 (8q), we examined 142 sporadic breast cancers for abnormalities in the copy-numbers of these loci. At each locus examined, a 2- to 3-fold increase in intensities of bands representing single alleles was observed in 57 (40%) of the tumors, indicating that 'multiplication' of the DNA sequence had occurred on 8q. A 16-cM region on 8q24.1 was commonly multiplied among the tumors with partial multiplications. Multiplication on 8q24.1 was observed more frequently in invasive solid-tubular or scirrhous tumors (48/92, 52%) than in less aggressive histologic types (7/25, 28%, P = 0.031). Thus, multiplication of tumor-promoting gene(s) located on 8q24.1 may play a role in the development and/or progression of a substantial proportion of primary breast cancers, particularly those of the invasive histology.

Alleles↗
PubMed1999

Localization of a tumor suppressor gene associated with the progression of human breast carcinoma within a 1-cM interval of 8p22-p23.1.

BACKGROUND: Frequent allelic losses on the short arm of chromosome 8 in several types of human cancers, and deletion maps of this region in tumor DNAs, have suggested that 8p harbors one or more genes that are important for suppressing tumorigenesis in the tissues in question. METHODS: To define the locations of potential tumor suppressor genes involved in breast carcinoma, the authors examined 144 primary breast carcinomas for loss of heterozygosity at 18 highly polymorphic microsatellite loci on 8p. They also sought correlations between allelic loss on 8p and several clinicopathologic parameters. RESULTS: Allelic loss was observed in 74 of the 144 sporadic breast carcinomas examined. Whereas more than half of the informative tumors showed loss of an allele at every locus on the short arm, 32 showed partial or interstitial deletions. Deletion mapping in this panel of tumors identified two distinct commonly deleted regions, one in a 1-cM interval flanked by D8S511 and D8S1991 at 8p22-p23.1, and the other in a 16-cM interval flanked by D8S136 and D8S1477 at 8p22-p21. Allelic losses in both of these regions were observed more frequently in tumors of the solid-tubular or scirrhous type than in less aggressive histologic types. Furthermore, allelic loss in either region occurred more frequently in larger and infiltrative tumors (T1 < T2 < T3). CONCLUSIONS: The association of allelic losses on 8p with advanced tumor stage and aggressive histologic type implies that loss or inactivation of one of at least two putative tumor suppressor genes on 8p may contribute to the progression of breast carcinoma.

Breast Neoplasms↗
PubMed1999

Frequent allelic loss at the TOC locus on 17q25.1 in primary breast cancers.

Sporadic breast cancers often show allelic losses on the long arm of chromosome 17. Since the BRCA1 gene lies at 17q21.1 and the TOC locus, associated with esophageal cancer, lies at 17q25.1, either gene could be the target of those losses. We examined both loci in 178 primary breast cancers, using microsatellite markers covering the relevant regions of 17q, and observed allelic losses in 97 tumors (55%). Losses were most frequent at markers around the TOC locus (48% at D7S1839 and 43% at D17S1603), where we identified a distinct commonly deleted region within a I -cM interval. Another larger, separate commonly deleted region including the BRCA1 gene was also identified, which exhibited 45% of allelic loss (at D17S934). Allelic loss on 17q was more frequent in tumors of the solid-tubular histologic type (P = 0.0129) and in estrogen-negative and progesterone-negative tumors (P = 0.0281 and 0.0196, respectively). The results indicated that BRCA1 and TOC are independent targets of allelic loss on 17q in primary breast cancers, and that inactivation of the TOC locus in particular may play an important role in the genesis of sporadic breast tumors.

BRCA1 Protein↗
PubMed1999

The location of positive nodes partly influences the prognostic value of the number of positive nodes in breast cancer patients.

BACKGROUND: The aim was to determine whether the number of positive lymph nodes or the location of lymph node metastasis (location number) would permit a more accurate prediction of prognoses. METHODS: We compared the survival rates of 3922 patients with primary breast cancer in relation to the location number and the number of positive lymph nodes. Survival rates were calculated by the Kaplan-Meier method and analyzed using the log rank test. RESULTS: Within the n1 alpha group, the presence of one or two positive nodes was associated with significantly better survival than the presence of three positive nodes. These groups should therefore be distinguished. Within the n1 beta group, there was no significant difference in survival between patients with four and those with seven or more positive nodes. Comparisons of n1 beta and n2 patients after subgrouping by the number of positive nodes (4-9 and 10 or more) revealed a significantly poorer prognosis in the n2 group. CONCLUSIONS: When the prognosis of breast cancer is considered from the viewpoint of lymph node metastasis, the location number as described in the General Rules is an excellent classification. However, we should be aware of possible differences in the prognosis depending on the number of positive nodes, as this is masked by the location number.

Adult↗