Concordance in judgments among c-erbB-2 (HER2/neu) overexpression detected by two immunohistochemical tests and gene amplification detected by Southern blot hybridization in breast carcinoma.

We compared the c-erbB-2 protein overexpression status detected by the HercepTestTM (DAKO A/S, Grostrup, Denmark) with another conventional immunohistochemistry system using an anti-c-erbB-2 rabbit polyclonal antibody (Nichirei Co., Tokyo, Japan) and with the c-erbB-2 gene amplification status detected by Southern blot hybridization in 101 surgically resected breast carcinomas. According to the criteria for overexpression, recommended by the manufacturer, c-erbB-2 overexpression by HercepTestTM was detected in 24 cancers (24%), comprising six score-2 tumors and 18 score-3 tumors.

Preferential occurrence of breast carcinomas with loss of chromosome 16q and der (16) t (1;16) / der (1;16) in middle-aged patients with hyperplasia of mammary glands.

Structural and numerical alterations of chromosome 16 are considered to be commonly involved in the genesis of breast cancer. To reveal etiological factors that predispose cells to these alterations, we examined the frequencies of chromosome 16 aneusomy, 16q loss and 1;16 fusion indicating der (16) t (1;16) / der (1;16) by multi-color fluorescence in situ hybridization in 46 tumors resected mostly from young ( /= 75 years old) women, and compared the results with those in a patient group representing a common age distribution of Japanese patients in whom chromosome 16 status in the tumor had already been studied. The correlation of these chromosome 16 alterations with age, hyperplasia in adjacent mammary glands, cancer history, and obesity indices was investigated in a total of 244 patients.

Dedifferentiated liposarcoma of retroperitoneum and mesentery: varied growth patterns and histological grades--a clinicopathologic study of 32 cases.

The purpose of this study was to obtain further information regarding cellular differentiation and proliferative characteristics of dedifferentiated liposarcoma (DDL) arising in the retroperitoneum and mesentery for accurate diagnosis and prognostic criteria. The patients included 20 men and 12 women, mean age, 60 years (range, 33 to 80 years). Twenty-seven tumors were located in the retroperitoneum and 5 in the mesentery.

Extrathoracic solitary fibrous tumors: their histological variability and potentially aggressive behavior.

The histological variability of solitary fibrous tumors may contribute to the difficulty in diagnosing these neoplasms, especially when they arise in extrathoracic sites. Like intrathoracic lesions, the behavior of extrathoracic solitary fibrous tumors is currently unpredictable because these types of tumor have only recently been recognized. This study therefore was undertaken to examine the clinical behavior and histological, immunohistochemical, and ultrastructural features of 24 extrathoracic solitary fibrous tumors with long-term follow-up.

Prognostic relevance of a histological grading system using MIB-1 for adult soft-tissue sarcoma.

Several histological grading systems have been proposed and found as strong indicators of outcome in soft-tissue sarcomas. However, a putative independent prognostic influence of recently developed biological and molecular markers remains to be established. This study investigated the prognostic relevance of a histological grading system based on the assessment of proliferative activity in adult soft-tissue sarcomas of the extremities, trunk, head, and neck.

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.

Heterotopic sebaceous glands in the esophagus: histopathological and immunohistochemical study of a resected esophagus.

A resected esophagus with numerous heterotopic sebaceous glands was examined in an attempt to determine whether esophageal heterotopic sebaceous glands are the result of a metaplastic process or a congenital anomaly. The present case concerns a 79-year-old Japanese man with numerous esophageal heterotopic sebaceous glands accompanied by superficial esophageal cancer. The resected esophagus possessed numerous heterotopic sebaceous glands, which could be seen clearly as slightly elevated, yellowish lesions.

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.

Detection of alterations in chromosomes 16 and 1 by fluorescence in situ hybridization in breast tumors cytologically or histologically equivocal for malignancy.

Structural and numerical alterations, and fusion of chromosomes 16 and 1 have been shown to occur frequently in low-grade breast carcinoma, but not in benign papilloma by fluorescence in situ hybridization (FISH). We carried out FISH analysis of 11 benign tumors and 3 breast tumors for which the preoperative diagnosis was equivocal for cancer. In 11 benign lesions and 1 benign phyllode tumor which was cytologically equivocal for malignancy, alteration of the chromosome 16 or 1 signal was not detected as a predominant cell clone.

Collagenous fibroma (desmoplastic fibroblastoma): report of four cases and review of the literature.

Background: Collagenous fibroma (desmoplastic fibroblastoma) is poorly recognized and may be mistaken for other benign or even malignant spindle-cell tumors of soft tissue because of the small number of reported cases.

Design: Collagenous fibromas resected from four adult women were studied histologically and immunohistochemically.

Results: The tumors were well-circumscribed firm masses, measuring from 1.

Prognostic significance of accumulation of gene and chromosome alterations and histological grade in node-negative breast carcinoma.

The histological grade of atypia is a known prognostic indicator for breast cancer patients and correlates with many gene and chromosome alterations. To investigate the independent prognostic significance of gene and chromosome alterations in axillary node-negative (n0) breast cancers of the invasive ductal and invasive lobular types, the prevalence of eight gene and chromosome alterations and their association with histological grade and recurrence was studied in 129 consecutive patients who had undergone resection over an average follow-up period of 43.4 months.

New chemotherapeutic agents for the treatment of non-small cell lung cancer: the Japanese experience.

Non-small cell lung cancer (NSCLC) is refractory to systemic chemotherapy, compared with small cell lung cancer. Until recently, only five drugs--cisplatin, vindesine, mitomycin, ifosfamide, and vinblastine--could produce overall response rates of 15% against NSCLC. However, recent efforts have contributed to the development of new drugs with activity against NSCLC, including irinotecan hydrochloride (CPT-11), paclitaxel, docetaxel, vinorelbine, and gemcitabine.

Detection of numerical and structural alterations and fusion of chromosomes 16 and 1 in low-grade papillary breast carcinoma by fluorescence in situ hybridization.

Intracystic papillary breast tumors, including intraductal papilloma and low-grade intracystic papillary carcinoma, constitute a group for which differential diagnosis is frequently difficult. We examined the status of chromosomes 16 and 1 by multicolor fluorescence in situ hybridization (FISH) analyses and the DNA ploidy patterns by flow cytometry in 26 intracystic papillary tumors. Alterations of chromosomes 16 and 1 were detected by FISH in 93 and 85%, respectively, of 14 low-grade papillary carcinomas, and the latter alterations always concurred with the former.

Epidermization in the esophageal mucosa: unusual epithelial changes clearly detected by Lugol's staining.

A 58-year-old Japanese man with superficial esophageal cancer accompanied by unusual epithelial changes, including esophageal mucosal epidermization, is reported. Staining with Lugol's iodine clearly showed irregular unstained lesions, which could not be seen clearly macroscopically, in the resected specimen. Histologic examination of the irregular unstained areas showed definite granular and horny layers regarded as epidermization, acanthosis with slight nuclear enlargement, and epithelial atrophy.

Squamoid features and expression of involucrin in primary breast carcinoma associated with high histological grade, tumour cell necrosis and recurrence sites.

Although breast carcinomas are considered to originate from glandular epithelial cells, some exhibit 'squamoid features', comprising stratification with a gradient in the nuclear-cytoplasmic ratio within individual cancer cell nests on microscopy. In parallel with a histological review of squamoid features, we immunohistochemically investigated the expression of involucrin, a marker of terminal squamous differentiation, in 223 breast carcinomas with one to three regional nodal metastases but no distant metastases and analysed their association with other clinicopathological parameters to explore their clinical and biological implications. Squamoid features and involucrin expression, detected in 22% and 27% of cases respectively, correlated with each other and were associated with high-grade atypia, a solid-nest pattern, cancer cell necrosis on histology and negative oestrogen receptor status.

Detection of allele loss on chromosome 16q in DNA isolated from fine needle aspiration specimens of breast tumors. A simulation study using surgically resected specimens.

Objective: To clarify whether analysis of loss of heterozygosity (LOH) on chromosome 16q is possible using DNA isolated from fine needle aspiration specimens, a simulation study was performed using resected biopsy or mastectomy specimens of 37 breast carcinomas and 3 fibroadenomas.

Study Design: A highly polymorphic (AC)n repeat region on the D16S305 locus on chromosome 16q24 was amplified in the DNA samples by the polymerase chain reaction (PCR) using 32P-labeled oligonucleotide primers, and the PCR products were electrophoresed in denaturing gel for detection of LOH by autoradiography.

Results: PCR was successful in 34 cases, and LOH was detected in 10 (71%) of 14 carcinomas but not in the 3 fibroadenomas.

Prognostic value of p53 protein accumulation in cancer cell nuclei in adenocarcinoma of the uterine cervix.

Adenocarcinoma of the uterine cervix (CxAd) is one of the most distressing malignancies of the female reproductive system because of its tendency to spread aggressively and to be resistant to radiation and systemic therapies. To clarify the prognostic significance of p53 alteration in CxAd, we immunohistochemically examined the incidence of p53 nuclear accumulation, which is considered to be mostly parallel with p53 gene mutation, and its association with clinicopathological parameters in 26 patients with CxAd. The overall incidence of p53 nuclear accumulation was 46% (12 of 26), being higher in groups with clinically advanced disease, higher degrees of cellular atypia, and deeper myometrial invasion, but significantly lower in patients with integration of human papillomavirus (HPV) type 16 or 18 DNA.

Frequent occurrence of c-Ki-ras gene mutations in well differentiated endometrial adenocarcinoma showing infiltrative local growth with fibrosing stromal response.

The frequency of c-Ki-ras mutation was examined by polymerase chain reaction (single-strand conformation polymorphism and direct sequencing analysis) and its association with histological parameters was analyzed in 110 endometrial adenocarcinoma hysterectomy specimens. The c-Ki-ras mutation was detected in 24 cases (22%). It occurred irrespective of tumor size, stage or histological grade, and was more frequent in tumors associated with endometrial hyperplasia (11 of 20, 55%) than in those without (10 of 73, 14%).

Pattern of gene alterations in intraductal breast neoplasms associated with histological type and grade.

To reveal any association between the histological type and grade of intraductal breast neoplasms and the manner of accumulation of gene alterations, eight types of gene alterations, i.e., loss of heterozygosity (LOH) on chromosomal arms 16p, 16q, 17p, 17q, and 18q, amplification of the c-erbB-2 and hst-1/int-2 genes, and mutation of the p53 gene, were examined by Southern blot analysis or single-strand conformation polymorphism analysis in a total of 60 cases of intraductal breast cancer and 18 nonmalignant proliferative lesions.

Malignant progression of adenomyoepithelial adenosis of the breast.

A case of breast tumor is described, which consisted of dense and uniform proliferation of ducts and lobules composed of both epithelial and myoepithelial cells and in which multiple foci of adenocarcinoma were observed. The tumor surrounding the carcinoma foci was identified as 'adenomyoepithelial adenosis'. Adenomyoepithelial adenosis was not monoclonal by clonal analysis, but revealed a relatively high labeling index for proliferating cell nuclear antigen by immunohistochemistry.

Allele loss on chromosome 16q24.2-qter occurs frequently in breast cancers irrespectively of differences in phenotype and extent of spread.

Loss of heterozygosity on chromosomal arm 16q has been shown to be a frequent event in sporadic breast cancer and is suggested to be involved in cancer development through inactivation of a tumor-suppressor gene. To specify the commonly deleted region in which the unknown tumor-suppressor gene is located, a deletion map of chromosome 16 was constructed for 78 breast cancers, using 27 polymorphic DNA markers. Loss of heterozygosity on chromosome 16q was detected in 38 of the tumors.

p53 mutations and c-erbB-2 amplification in intraductal and invasive breast carcinomas of high histologic grade.

In order to clarify the clinical significance of mutations of the p53 gene and amplification of the c-erbB-2 gene in breast carcinoma, these gene alterations were examined in 101 invasive, seven predominantly intraductal and 10 intraductal breast carcinomas by single-strand conformation polymorphism-direct sequencing or Southern blot-hybridization analysis. p53 mutations were detected in 32 (32%) of the invasive cases and two (12%) of the 17 intraductal/predominantly intraductal cases, whereas c-erbB-2 amplification was detected in 14 (14%) of the invasive and six (35%) of the intraductal/predominantly intraductal cases. Irrespective of differences in the positions and types of the mutations, cases carrying p53 mutations were almost always Grade 3 histologically and with a low hormone-receptor value.

Prognostic factors for recurrent breast cancer: univariate and multivariate analyses including histologic grade and amplification of the c-erbB-2 proto-oncogene.

Post-recurrence survival was examined in 62 breast cancer patients who had undergone curative radical mastectomies between 1974 and 1976 and suffered recurrences within 127 months of surgery. The prognostic value of 11 clinical, histological and genetic factors, including histologic grade of malignancy and amplification of oncogenes was analyzed using univariate and multivariate analyses. Not only the site of first recurrence, clinical stage and size of primary tumor at initial surgery, and disease-free period, but also histologic grade and amplification of the c-erbB-2 proto-oncogene were significant prognostic indicators of recurrent breast cancer.

Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis.

Mutations of the p53 gene were investigated after tumor cell enrichment by cell sorting based on differences in DNA content and polymerase chain reaction single-strand conformation polymorphism analysis in 24 surgical specimens of primary gastric cancer. p53 mutations were detected in exons 4-8 in 64% (9 of 14) of aneuploid tumors but in none of 10 diploid tumors examined. Four of five tumors containing two or three aneuploid subpopulations showed the presence of p53 gene mutations.

Point mutation of c-Ki-ras oncogene in gastric adenoma and adenocarcinoma with tubular differentiation.

The presence of point mutation at codons 12, 13 and 61 of the c-Ki-ras oncogene was investigated in 7 cases of gastric adenoma and 35 cases of gastric adenocarcinoma using DNA samples from formalin-fixed and paraffin-embedded tissues. Oligonucleotides encompassing the three codons were amplified by using the polymerase chain reaction (PCR), and then examined for point mutation by the selective oligonucleotide hybridization technique. Point mutation was detected in three of the 7 adenomas (43%) and three of the 35 carcinomas (9%).