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).

[Myeloperoxidase-antineutrophil cytoplasmic antibody positive alveolar hemorrhage during propylthiouracil therapy for hyperthyroidism].

A 62-year-old woman had been treated with propylthiouracil(PTU) for hyperthyroidism. Because bloody sputum, dyspnea, and severe hypoxemia developed, the patient was admitted to our hospital. Chest X-ray and chest computed tomographic (CT) films disclosed diffuse infiltrative shadows in both lung fields.

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.

Evaluation of the interobserver agreement in the number of mitotic figures of breast carcinoma as simulation of quality monitoring in the Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) protocol.

In the National Surgical Adjuvant Study for Breast Cancer (NSAS-BC), node-negative breast cancers were divided into higher- and lower-risk groups according to the histopathological nuclear grade given at individual collaborating hospitals, and the higher-risk group was entered into a randomized protocol of adjuvant therapy. Because the nuclear grade was the composite of nuclear atypia and mitotic counts, maintenance of interobserver agreement in mitotic counts was indispensable for the success of the protocol study. Fourteen pathologists participating in the protocol judged whether or not 20 photomicrographs suspected of showing mitotic cancer-cell figures truly showed mitoses.

A quantitative model using mean and standard deviation for evaluation of interobserver agreement in nuclear atypia scoring of breast carcinomas in a protocol study.

A quantitative model was devised for the purpose of evaluating interobserver agreement in the judgment of the nuclear atypia score of cancer cells in protocol studies. In this model, the mean nuclear atypia score (mu) among observers was considered to approximate the 'true' nuclear atypia score of the tumor, and with an identical mu the strength of interobserver agreement was evaluated by the difference between the ideal standard deviation (sigma) and the observed sigma in the slide conference session. This model was applied to the data of a total of 216 invasive ductal carcinomas acquired at eight slide conference sessions held for the standardization of nuclear atypia scoring and monitoring of interobserver agreement level for enrolled cases in a surgical adjuvant protocol on breast cancer.

Utility of the monoclonal antibody HIK1083 in the diagnosis of adenoma malignum of the uterine cervix.

Objectives: The aim of this study was to qualify a staining technique for the diagnosis of adenoma malignum.

Methods: The gastric mucin expression of adenoma malignum, ordinary endocervical adenocarcinoma, and normal cervical glands was immunohistochemically compared using the monoclonal antibody HIK1083.

Results: The three categories were clearly distinguished, with 90% (9/10) of cases with positive adenoma malignum, 30% (3/10) of cases with weakly positive ordinary cervical adenocarcinoma, and no (0/10) cases of positive normal cervical glands.

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.

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.

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.

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.

The efficacy and limitations of repeated slide conferences for improving interobserver agreement when judging nuclear atypia of breast cancer. The Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) Pathology Section.

Background: The pathology section of the Japan National Surgical Adjuvant Study of Breast Cancer protocol study was set up to establish histological criteria for assessing high-risk node-negative breast cancers and standardize the subjective criteria used by collaborating pathologists for nuclear grading of cancers.

Methods: In order to standardize the nuclear atypia criteria, five slide conferences were held. A total of 57 observers assigned nuclear atypia scores to 119 breast carcinomas that were presented using a slide projector or a TV monitor and discussed their histological findings.

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.

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.

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.

A clinicocytopathologic study of adenoma malignum of the uterine cervix.

Objectives: To investigate the nature and the clinical course of adenoma malignum (the so-called minimal deviation adenocarcinoma) of the uterine cervix by conducting a retrospective study of 6 cases consecutively treated in a single institute.

Methods: The pathologic classification of adenoma malignum was performed according to the WHO classification (1994).

Results: These tumors accounted for only 1.

The possible prognostic significance of p53 immunostaining status of the primary tumor in patients developing local recurrence after breast-conserving surgery.

Prognostic factors for distant metastases in patients with local recurrence after breast-conserving treatment (BCT) were studied. Fifty-six patients who developed local recurrence after BCT were recruited from 18 key hospitals/institutes in Japan. All 10 patients whose primary tumors were DCIS fared well without evidence of distant failure for a median follow-up period of 57 months (range 41-72) after the local recurrence.

Toward the development of a universal grading system for ovarian epithelial carcinoma. I. Prognostic significance of histopathologic features--problems involved in the architectural grading system.

Objective: Because there is no universally accepted grading system for ovarian epithelial carcinoma, we attempted to compare the prognostic utility of the individual components used in some systems--both architectural and cytologic features, as well as mitotic activity and histologic tumor type--to determine which of these components fit best with survival.

Methods: We studied 461 patients with invasive ovarian carcinoma who had uniform treatment, complete clinical data including staging and follow-up, and slides available for review. Each tumor was assigned a histologic subtype, architectural grade (based on whether the predominant pattern was glandular, papillary or solid), nuclear grade, mitotic count, and FIGO grade (based on the system for endometrial carcinoma).

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.

[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.

Combination of consecutive low-dose cisplatin with bleomycin, vincristine, and mitomycin for recurrent cervical carcinoma.

Purpose: To evaluate the efficacy and toxicity of combination chemotherapy with bleomycin, vincristine, mitomycin, and consecutive low-dose (CLD) administration of cisplatin (CLD-BOMP) for patients with recurrent cervical carcinoma.

Patients And Methods: Ninety patients with recurrent cervical carcinoma and no prior chemotherapy were enrolled onto this study. The median age was 56 years.

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.

Toward the development of a universal grading system for ovarian epithelial carcinoma: testing of a proposed system in a series of 461 patients with uniform treatment and follow-up.

Background: Most published series of ovarian carcinoma find a correlation between histologic grade and survival, but the grading system used commonly is not specified, and several different systems exist, some of which use different criteria for different histologic types. However, several studies have shown marked interobserver variability in distinguishing among the histologic types of ovarian carcinoma. The authors attempted to derive a universal grading system for all invasive ovarian carcinomas (IOC), based on the Nottingham system for grading all types of mammary carcinoma.

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.

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.

A case-control study on risk factors for local recurrences or distant metastases in breast cancer patients treated with breast-conserving surgery.

A case-control study was conducted on 143 case-control sets recruited from the 18 key hospitals/ institutes in Japan to identify risk factors for local recurrences and distant metastases after breast-conserving surgery in breast cancer patients: (1) positive surgical margin was a risk factor for local recurrences (relative risk (RR) = 16.70, p < 0.001) but not for distant metastases, (2) positive p53 immunostaining was a risk factor for both local recurrences (RR = 5.