Shunsuke Haga

Relationship between the morphological and biological characteristics of intraductal components accompanying invasive ductal breast carcinoma and patient age.

We divided 324 cases with invasive ductal breast carcinoma into three age groups, and investigated the differences in proliferative activity and extension of the intraductal components among the age cohorts. Proliferative activity was expressed as the number of MIB 1-positive nuclei per 1000 cancer cells in the intraductal components (MLI), and the intraductal component extension farthest from the invasive focus was defined as the maximum distance of ductal spread (MXDS). Moreover, analyses were conducted for three grade types, classified according to the classification system of ductal carcinoma in situ. The under-40 age group had significantly higher MXDS values than the other two age groups (p = 0.0280), and this trend was more marked in those with the non-high grade without necrosis type (p = 0.0045). The under-40 age group had higher MLIs, but the differences did not reach statistical significance (p = 0.0793). In regard to those with the high grade type, the under-40 age group had significantly higher MLIs than the other two age groups (p = 0.0269), and this trend was not significant in the cases with any other grade types. Associations between the age group and the margin status of the lumpectomy specimens were investigated in the 143 cases in which breast conserving surgery was tried. The under-40s had a significantly higher margin-positive rate in their lumpectomy specimens than the other two age groups (p = 0.0362), and this trend was also seen in the groups with the non-high grade without necrosis type (p = 0.0256). These results confirm the importance of considering patient age when designing surgical procedures for breast conserving therapy.

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.

Radiotherapy with concurrent docetaxel for advanced and recurrent breast cancer

BackgroundDocetaxel has shown remarkable radiosensitizing propertiesin vitro. In this study we investigated whether the addition of docetaxel to radiotherapy enhanced tumor response in patients with advanced or recurrent breast cancer.MethodsA total of 35 patients were enrolled in this study. Docetaxel was administered concurrently during radiotherapy. Radiation doses were 54 to 69 Gy (median 60 Gy). In those enrolled through January 2000, docetaxel 40 mg/m2 was administered biweekly (once every two weeks), with subsequent dose adjustments based on tolerance and bone marrow and liver function. Beginning in February 2000, a weekly docetaxel schedule was used instead. This new regimen was based on data suggesting reduced myelosuppression with this regimen. The weekly dose rate was 20 mg/m2, with dose reductions for impaired organ function.ResultsAll patients were evaluated for toxicity and response and a total of 40 irradiated sites were evaluated for local response. The overall response rate of irradiated sites was 95% and the CR rate was 68%. CR and PR were achieved in 40%, 37% of patients, respectively. Acute toxicities were tolerated by most patients: 17% had Grade 3-4 neutropenia, 6% had Grade 3-4 radiation dermatitis, and 3% had Grade 3-4 pneumonitis.ConclusionThe combination of docetaxel with radiotherapy is an active and safe regimen in patients with inoperable advanced or recurrent breast cancer. We determined the recommended dose of docetaxel with concomitant radiotherpy to be 20 mg/m2 weekly for a Phase II study. Further study is necessary to assess the impact of this treatment on long-term outcome.

Histopathological study of local residual carcinoma after simulated lumpectomy

From 1989 to 1991, 24 patients with invasive ductal carcinoma underwent simulated lumpectomy at Tokyo Womens Medical College Daini Hospital. The mastectomy specimens were then examined histopathologically in serial sections for the presence of residual tumors or multicentricity. Lumpectomy specimens from cancer foci at resected margins were also examined. In this study, 23 of 24 patients demonstrated positive resection margins (95.8%). Residual tumors were found in mastectomy specimens from 16 patients (66.7%); unilateral multifocal carcinomas were found in 2 of these patients (8.3%). The incidence and severity of residual tumors did not correlate with primary tumor size or the distance between the nipple and the primary tumor but directly correlated with the severity of intraductal spread of the primary tumor. Tumors with central necrosis were associated with a higher incidence of residual tumors. Our study thus indicates that there is a high risk that some residual tumor will be left in the conserved breast when lumpectomy is performed. Multifocal carcinoma and tumors showing severe intraductal spread and central necrosis are thus associated with extensive residual tumors and are likely to cause local recurrence.

Adenocarcinoid of the Appendix: Report of Two Cases

Abstract.Adenocarcinoid of the appendix is a rare tumor with the histological features of both adenocarcinoma and carcinoid tumor. However, its biological behavior and malignant potential are still unclear. We treated two patients with this unusual tumor; a 60-year-old man and a 79-year-old woman. Both patients were initially diagnosed with acute appendicitis followed by an appendectomy. At surgery, the appendix was seen to be acutely inflamed without any macroscopic signs of tumor. Postoperative histological analysis revealed an adenocarcinoid tumor in the appendix, which had spread diffusely into its wall without forming a mass. Immunohistochemical staining with p53, MIB-1, bcl-2, and carcinoembryonic antigen suggested that neither of these tumors were particularly aggressive. Adenocarcinoid of the appendix is a rare tumor, which is very difficult to diagnose preoperatively and even macroscopically, making histological examination essential.

Breast cancer in a male patient with prolactinoma

A 68-year-old manw as diagnosed as having left primary breast cancer. Systemic bone roentgenography showed no evident metastasis, however, skull roentgenography revealed ballooning of the sella turcica, suggesting a pituitary tumor, which was subsequently confirmed by computed tumography. Because there was a high serum prolactin level, the pituitary tumor was diagnosed as a prolactinoma. A modified radical mastectomy was performed for the breast cancer, and bromocriptine therapy given for the prolactinoma. Prolactin is known to initiate and promote breast cancer in mice and rats but little is known about its role in human breast cancer. If hyperprolactinemia plays an important role in the tumorigenesis of human breast cancer as it does in mice and rats, the incidence of breast cancer in patients with hyperprolactinemia may be high. To our knowledge, however, only four such cases have been reported. The present rare case of male breast cancer with prolactinoma is discussed with reference to the literature.

Allelic losses as prognostic markers for breast cancers

Abstract Specific allelic losses in the DNA of tumor cells are potential indicators of postoperative prognosis. Patients whose tumors showed allelic losses at 1p34, 3p25, 8p22, 13q12, 17p13.3, or 17q21.1 had a significantly higher risk of postoperative mortality than women whose tumors retained both alleles at those loci (the 5-year mortality rates in patients with loss vs those with retention were: at 1p34, 23% vs 10%, 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). Allelic losses at these loci may serve as negative prognostic indicators to guide postoperative management, especially in the selection of patients who should be offered intensive adjuvant therapy.

The expression of variant exon v7-v8 CD44 antigen in relation to lymphatic metastasis of human breast cancer

The purpose of this prospective study was to evaluate the expression of CD44 splice variant epitopes in human breast cancer and their potential as prognostic indicators.Invasive breast cancer tissues obtained from 91 patients were examined for expression of the standard CD44 antigen and variant CD44 antigens (v5, v6, v7, v7–v8, and v8–v10) by immunohistochemical staining to investigate the relations of these antigens to clinicopathological factors and prognosis.The expression of standard CD44 antigen was detected in 54.9% of 91 patients with primary human breast cancer. The variant epitopes of CD44 examined, i.e., v5, v6, v7, v7–v8, and v8–v10, were expressed in 54.9%, 54.9%, 0%, 34.1%, and 0%, respectively. There was a significant difference in tumor size, lymph nodal status, and degree of lymphatic permeation between patients who were positive for exon v7–v8 and those negative for this variant (p < 0.01). Prognosis was also significantly worse in patients positive for CD44 v7–v8 than in those negative for this variant. However, multivariate analysis with the three prognostic indicators tumor size, lymph nodal status, and the degree of lymphatic invasion, has shown that the expression of CD44 v7–v8 antigen in breast carcinoma was not a significant independent prognostic factor and was closely dependent on lymphatic invasion and nodal status. Fourteen of 31 patients who were positive for CD44 v7–v8 experienced recurrences. The mode of recurrence was lymphatic metastasis in 10 out of these 14 patients. Breast cancer cells expressing v7–v8 CD44 antigen have an extremely high affinity for lymph nodes and lymphatic vessels, and are likely to metastasize to distant lymph nodes even at a very early stage in the progression of this disease. This suggests that not only the anatomical factors but also organ affinity plays an important role in the establishment of lymph nodal metastasis of breast cancer.

A Case of Benign Schwannoma of the Transverse Colon with Granulation Tissue

Schwannomas occurring in the gastrointestinal tract are rare, and among them, schwannomas of the large intestine are extremely rare. In this paper, we report a case of a macroscopically atypical schwannoma of the transverse colon. The case is a female aged 67. Stool occult blood test was positive, and colonoscopy revealed a protruded lesion resembling a type 1 carcinoma measuring 4 cm with a reddish and uneven surface on the transverse colon. The surface was smooth and lobulated in observation with indigo carmine spray, and granulation tissue was revealed by biopsies. CT of the abdomen showed an irregular mass, and clinical examinations could not rule out malignancy. Therefore, partial transverse colectomy with peripheral lymph node dissection was performed. Histologically, proliferation of spindle cells was observed originating from the muscularis propria, and most of the upper part of the lesion was replaced by granulation tissue. In immunohistochemical staining, S-100 protein and NSE were positive while KIT, CD34, desmin and smooth muscle actin were negative, and the tumor was therefore diagnosed to be a schwannoma. In addition, since the MIB-1 labeling index was low and virtually no mitosis was observed, it was diagnosed as benign tumor.

Acinic Cell Adenocarcinoma Arising in the Breast of a Young Male: A Clinicopathological, Immunohistochemical and Ultrastructural Study.

A 23-year-old man with acinic cell adenocarcinoma of the breast is reported. He presented with a 4.8 × 4.2 cm mass in his left breast, and excisional biopsy was performed. Under the light microscope, tumor cells had abundant periodic acid-Schiff-positive secretory granules and eosinophilic cytoplasms. Electron microscopy revealed the granules to have various electron densities, a finding characteristic of acinic cell adenocarcinoma. Immunohistochemically, the tumor cells were stained with salivary-type amylase. Electron microscopic and immunohistochemical investigation greatly facilitated the diagnosis of this acinic cell adenocarcinoma, which was in an unusual location. We believe this is the first case report of acinic cell adenocarcinoma of the mammary gland studied utilizing light microscopic, ultrastructural and immunohistochemical techniques.