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The aim of the present paper was to investigate the most adequate method for the assessment of hormone receptor status in breast cancer in routine clinical settings. Subjects were 486 patients with primary breast cancer who underwent surgery and postoperative tamoxifen monotherapy in 1982-1993. Using representative sections of the primary lesion in each patient, estrogen receptors (ER) were immunohistochemically stained. Patients were divided into ER-positive and ER-negative groups using various methods, and then overall and 5 year recurrence-free survival rates were compared. The results of ER status, which are diagnosed on entire cancer area and invasive cancer area, matched in 98% of cases. When assessing prognosis based on the proportion of positive cells, a significant difference in 5 year recurrence-free survival was seen between ER-positive and ER-negative patients for a cut-off of 10%, and in overall and 5 year survival for a cut-off of 33%. Based on the proportion and the intensity of positive cells (Allred score), a significant difference was seen in overall and 5 year survival for a cut-off in total scores between 4 and 5 points. When assessing hormone receptors of breast cancer in routine clinical settings, it is sufficient to determine the proportion of positive cells in the entire cancer area.

Background: To establish tailor-made therapy for breast cancer, we investigated the possibility of predicting chemotherapy sensitive cases based on pre-therapeutic histological features., Methods: A total of 87 breast cancer patients underwent neoadjuvant chemotherapy with a paclitaxel (80 mg/m(2)/q1w, 12 courses)or an epirubicin regimen (90 mg/m(2)/q3wks, 4 courses). We investigated the chemo-sensitivity of invasive ductal carcinoma, solid-tubular carcinoma consisting of highly malignant cancer cells with many mitoses. We refer to this type of carcinoma as " chemo-sensitive carcinoma " and compared the histological therapeutic effects of chemo-sensitive and chemo-insensitive carcinomas., Results: 1) Out of 87 patients, 20 cases (23%) showed the histological features of chemo-sensitive carcinomas on pre-therapeutic needle biopsy specimens. The remaining 67 cases (77%) were classified as chemo-insensitive carcinoma. 2) Histologically marked or complete response were observed in 50% (10/20) of chemo-sensitive carcinomas and 10% (7/67) of chemo-insensitive carcinomas (chi(2)=15.33, p=0.0001). Multivariate analysis of chemo-sensitive carcinoma, including HER2, hormone receptor and p53 status, revealed that chemo-sensitive carcinoma had a significant correlation with the histological therapeutic effects (p=0.01119). 3) Pathological complete response (pCR) was achieved in 35% (7/20) of chemo-sensitive carcinomas and 1.5% (1/67)of chemo-insensitive carcinomas (chi(2)=20.71, p<0.0001). Multivariate analysis revealed that chemo-sensitive carcinoma had a significant correlation with pCR (p=0.0091)., Conclusion: The histological features of chemo-sensitive carcinoma were significant predictive factors for chemotherapeutic efficacy.

A very rare case of muco-epidermoid carcinoma of the breast is reported. A 54-year-old woman noticed a breast lump and consulted the Cancer Institute Hospital, Tokyo. Physical examination revealed a mass with an unclear margin in the upper outer area of the left breast. Both mammography and ultrasonography showed an irregularly shaped mass, suggesting invasive carcinoma. Aspiration cytology revealed solid clusters of two types of cancer cells: ones with mucus in the cytoplasm, and others without mucus. Cytological features resembled muco-epidermoid carcinoma of the salivary gland but it was not possible to establish a diagnosis of the histological type because muco-epidermoid carcinoma of the breast had not previously been encountered by the authors. After incisional biopsy, left mastectomy with axillary lymph node dissection was performed. Histologically the tumor was surrounded by a fibrous pseudocapsule and was composed of intraductal carcinoma foci and invasive cancer nests. Intraductal carcinoma foci were the low papillary type. Stromal invasion showed many solid nests composed of mucus-containing and squamoid cancer cells. There was no common invasive ductal carcinoma component in this tumor. These histological features confirmed the diagnosis as muco-epidermoid carcinoma of the breast. This is the first report of muco-epidermoid carcinoma of the breast in Japan.

The recent decoding of a number of animal genomes has provided unprecedented information regarding evolution and gene structures, but this information must be supplemented with precise gene annotations and the temporal and spatial expression patterns of individual genes. In the present study, we systematically identified and characterized 566 zinc finger genes in the genome of Ciona intestinalis, an emerging model system for genome-wide studies of development and evolution. Of these genes, 356 genes encoded a potential transcription factor based on putative nucleic acid binding activity or domains of unknown function. We further examined the expression patterns of 225 genes during embryogenesis, and, when considered with a previous study [Imai, K.S., Hino, K., Yagi, K., Satoh, N., Satou, Y., 2004. Gene expression profiles of transcription factors and signaling molecules in the ascidian embryo: towards a comprehensive understanding of gene networks. Development 131, 4047-4058], we have characterized the developmental expression patterns of nearly 85% of the potential zinc finger-containing transcription factors. Overall, zinc finger genes are preferentially maternally expressed with little larval expression during development. The present study provides a valuable reference for genome-wide studies in this species and for future studies wishing to examine zinc finger gene expression patterns in other animals.

A patient with intraductal papilloma who had abnormal bloody discharge from Montgomery's areolar tubercle underwent mammary ductography, mammary ductoscopy from the tubercle, and microdochectomy.A 43-year-old woman who was being followed-up for left breast cancer noticed bloody discharge from Montgomery's areolar tubercle of the right breast. Because the discharge continued for 2 months, further examinations were conducted. Mammary ductoscopy of Montgomery's areolar tubercle showed a normal internal duct structure. The presence of yellowish superficial lesions suggested intraductal inflammation or superficial hyperplasia of the duct epithelium. Lavage cytology revealed benign papillary lesions. Since the discharge continued and we could not completely exclude malignancy, microdochectomy was performed. Histologically a lactiferous duct was connected to Montgomery's areolar tubercle and an intraductal papilloma was seen in part and considered to have caused the bloody discharge. Bloody discharge from Montgomery's areola tubercles is extremely rare, the present case was our first experience with ductoscopy of Montgomery's areolar tubercle out of 641 cases of mammary ductoscopy performed on patients with bloody nipple discharge from 1998 to 2004. In our case, Montgomery's areolar tubercles were connected to a lactiferous duct. Although there are a few breast carcinomas that cause bloody discharge and eruption of areola, areolar preservation should be performed with the knowledge that disease may also involve the areola through the lactiferous ducts.

Background: Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. Although the survival of patients with IBC has been greatly improved by the use of combined treatment modalities, women with IBC still have lower survival rates. We have summarized a single-center experience involving IBC patients. Our objectives are to clarify molecular alterations of HER-2/neu and p53 in IBC and to investigate the prognostic factors., Methods: Between January 1990 and December 2000, 57 patients with IBC were referred to the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The incidence of IBC among primary breast cancers was 1.0% (57/5,757) in our hospital. Forty-six patients meeting Haagensen's criteria for inflammatory breast carcinoma were evaluated. All patients had biopsy-proven carcinomas but no distant metastases at referral. The median age at diagnosis for IBC was 51.8 (range, 28 to 70). All patients underwent a mastectomy. Chemotherapy was performed pre- or post-operatively. Three-year and 5-year survival rates were 56.5%, and 40.7%, respectively. Expressions of HER-2/neu and the p53 protein were determined retrospectively by immunohistochemical (IHC) staining of thin paraffin-embedded sections of primary tumors., Results: Of 46 patients, 23 (50.0%) with tumors testing positive for HER-2/neu fared somewhat worse than those with negative tumors, but the differences were not significant for either overall survival (OS) or disease-free survival (DFS). Of 46 patients, 19 (41.3%) whose tumors were positive for p53 fared somewhat better than patients with negative tumors, with no significant differences in either OS or DFS. Patients presenting with less than ten pathologically involved axillary lymph nodes showed significantly better OS and DFS., Conclusions: Overexpression of HER-2/neu and the p53 protein were not significant prognostic factors in inflammatory breast cancer. However, the increased incidence of HER-2/neu and the poor outcome of IBC may be of clinical interest, suggesting the need for clinical trials of antibody therapy targeted to HER-2/neu. Moreover, a high prevalence of p53 may be useful in determining the specific use of chemotherapy.

The widespread use of screening mammography has resulted in increased detection of nonpalpable breast lesions here in Japan. For the histopathologic work-up of these lesions, stereotactic core biopsy is essential as a minimally invasive diagnostic procedure. However, the number of facilities that provide this procedure cannot keep up with the increasing demand from patients. Another issue is interpreting the results of the biopsy. With a histological diagnosis using needle samples, there is always a risk of underestimation or a false-negative result. To avoid missing cancers after stereotactic biopsy, it is important to check for sampling errors and for discrepancies between the radiologic and pathologic findings. We are pushing for the rapid spread of an ideal form of stereotactic breast core biopsy (using prone-type units, digital methods, and vacuum-assisted breast biopsy devices) throughout Japan so that every patient can undergo this examination.

Background: Healing is a phenomenon by which the intraductal component of breast cancer disappears and is replaced by fibrous tissue. Focally localized healing often prevents confirmation of the continuity of intraductal carcinoma., Objective: To clarify the clinicopathological characteristics of breast cancer with healing., Patients and Methods: At our hospital, 308 patients (311 breasts) underwent breast conservation therapy without neoadjuvant chemotherapy for breast cancer in 2000. These surgical specimens were histopathologically investigated with 5 mm serial sections. We assessed the proportion and the characteristics of breast cancer with healing., Results: (1) The proportion of breast cancer with healing was 7% (21/311). (2) In the 21 patients, the mean age was 59.2 years, and the mean diameter was 2.8 cm. (3) The histological type of the breast cancer varied: noninvasive ductal carcinoma in 2 cases, papillotubular carcinoma in 5, solid-tubular carcinoma in 8, scirrhous carcinoma in 5, invasive lobular carcinoma in 1, and Paget's disease in 1. However in all cases, the histologic type of the intraductal carcinoma foci was the comedo/solid type and the nuclear grade of cancer cells was high. (4) In cases with healing, areas of healing were seen in an average of 5 (1-26) blocks, compared with intraductal carcinoma foci in 13 blocks (2-40). Healing was located on the nipple side of the main lesion in 8 cases, the peripheral side in 9, and both sides in 4. In 3 cases, healing was seen at the surgical margin of the partial mastectomy specimen., Conclusion: The proportion of breast cancer cases with healing was 7% and these cases were intraductal carcinoma of the comedo/solid type, consisting of highly malignant cancer cells.

Carcinosarcoma is a rare malignant tumor of the breast. A 59-year-old woman was admitted to our hospital with a complaint of a right breast mass for one month. The mass grew rapidly, and modified radical mastectomy was performed. Based on the histological findings of carcinomatous and sarcomatous components entangled without a transition area, and the results of immunohistochemical staining, carcinosarcoma of the breast was diagnosed. Within 9 months of the surgery, a recurrent lesion appeared in her chest wall. As shown by local resection, this recurrent tumor had only a carcinomatous component. Such tumors are very rare, and there have been no detailed reports of recurrence patterns of carcinosarcoma. Here we report our pathological findings in detail.

A 45-year-old woman with malignant fibrous histiocytoma (MFH) of the breast following breast conserving therapy (BCT) is described. She noticed a lump in her left breast 52 months after BCT for breast cancer. The lump was excised and nodular fasciitis was initially diagnosed. However, the tumor recurred locally 4 times in the next 18 months. MFH was finally diagnosed. This case is considered to be radiation-induced sarcoma. The risk of radiation-induced sarcoma after BCT seems to be very low, however careful follow-up is necessary.