Kuniyoshi Tamaki

Nuclear p53 immunoreaction associated with poor prognosis of breast cancer

p53 protein has been frequently detected at high levels in the nuclei of human breast cancer cells. We analyzed inununohistochemically the association between nuclear localization of p53 protein and clinical and histological parameters of breast cancer patients. Surgically resected tissues of 73 primary breast cancers were processed by acetone fixation and paraffin embedding and examined using an anti‐p53 monoclonal antibody, Pabl801. p53 immunoreactivity was detected in the nuclei of cancer cells in 17 cases (23%). The nuclear p53 immunoreaction was closely associated with overexpression of c‐erbB‐2 protein (P<0.05), high histologic grade (P<0.01), advanced clinical stage (P<0.05), and negative estrogen receptor status (P< 0.01). When 31 cases which had been followed up for more than 50 months were examined, a positive nuclear p53 immunoreaction was found to he significantly associated with shorter overall survival of patients (P<0.01). These results suggest that inununohistochemical examination of nuclear p53 protein is clinically useful as an indicator of breast cancer aggressiveness.

Correlation of KIT and EGFR overexpression with invasive ductal breast carcinoma of the solid‐tubular subtype, nuclear grade 3, and mesenchymal or myoepithelial differentiation

Although KIT and EGFR overexpressions are reported to occur in breast cancer, their pathological significance is still unclear. We examined KIT, EGFR, and c‐erbB‐2 overexpressions immunohistochemically in 150 cases of surgically resected breast cancer and their correlation with the histological type and grade and mesenchymal and/or myoepithelial immunophenotype of primary tumors. To facilitate the analysis, we constructed a tissue microarray comprising 2‐mm diameter tissues cored from the representative tissue block of each tumor. KIT, EGFR, and c‐erbB‐2 overexpressions were detected in 15 (10%), 12 (8%), and 23 (15%), respectively. The KIT was more frequent in the group comprising comedo‐type ductal carcinoma in situ and invasive ductal carcinomas (IDCs) of the solid‐tubular subtype than in the group of other histological types (P = 0.027), and the EGFR was more frequent in IDCs of solid‐tubular type than in other histological types (P < 0.05). KIT and EGFR overexpressions were correlated with nuclear grade 3 (P = 0.0095 and 0.0005) and tended to be concurrent (P = 0.005). KIT overexpression was correlated with vimentin and S‐100 expression (P = 0.003 and P = 0.005), and EGFR overexpression was correlated with S100 expression (P = 0.0001). These correlations with grade and mesenchymal/myoepithelial markers were not observed for c‐erbB‐2 overexpression. KIT and EGFR appeared to be indicators of high‐grade breast carcinoma groups that often contain the carcinomas with mesenchymal and/or myoepithelial differentiation, which are distinct from the group with c‐erbB‐2 overexpression. (Cancer Sci 2005; 96: 48 –53)

Primary small cell (oat cell) carcinoma of the breast: Report of a case and review of the literature

A case of primary small cell (oat cell) carcinoma of the breast in a 41‐year‐old woman is presented. The patient was alive and well without disease 16 months after modified radical mastectomy and subsequent chemotherapy. The tumor cells revealed morphologic similarity to oat cell carcinoma of the lung and immunohistochemical expression of neuroendocrine markers. In ultrastructural examination, the tumor cells had neurosecretory granules. Review of nine previously reported cases and this case of primary small cell carcinoma of the breast has revealed that this type of tumor shows prominent vascular invasion, frequent lymph node metastasis, infrequent expression of estrogen receptor, and also very poor prognosis. Immunohistochemical study for the c‐kit proto‐oncogene product, which has been reported to be a specific marker for pulmonary small cell carcinoma, demonstrated positive reactivity in approximately 80% of the tumor cells of this case, which is the first report according to our knowledge. The expression of c‐kit might be some aid to the diagnosis of primary small cell carcinoma of the breast.

Efficacy and Significance of Sentinel Lymph Node Identification with Technetium-99m-labeled Tin Colloids for Breast Cancer

PurposeThe sentinel lymph node (SLN) is thought to reflect the metastatic status of the remaining axillary lymph nodes in patients with breast cancer. We used technetium-99m-labeled tin colloids to identify SLN. The efficacy and significance of SLN identification using this method were investigated in terms of number, size, location, and tumor metastasis. The efficacy of the emulsion charcoal injection method for the intraoperative visible identification of SLN was also evaluated.MethodsTwenty-five patients with invasive breast cancer were studied. Under ultrasonographic guidance, technetium-99m-labeled tin colloid particles (3 ml) were injected into 3 sites around the tumor within 3 mm of the margin or into the wall of the excisional biopsy cavity 2 hours before surgery. At surgery, just before the incision, an emulsion of charcoal particles (2.5 ml) was injected into 3 sites of the breast parenchyma surrounding the tumor. All patients underwent mastectomy with axillary dissection to the infraclavicular region. The radioactivity of each dissected lymph node was measured. All axillary specimens were processed in individual blocks for permanent section histopathologic evaluation with H &E.ResultsSLN were defined as lymph nodes with 100 000 or more counts per minute (cpm) in radioactivity after injection of labeled tin colloids. In all 25 patients, SLN were identified (mean, 1.9 SLN/patient; range,l-4). Since the mean uptake in SLN was 383 124 cpm, but only 884 cpm in non-SLN nodes, discrimination between SLN and non-SLN nodes was easy. Clearly visible lymph nodes with charcoal staining accounted for 83.3% of all SLN, although 21.3% of non-SLN also stained. SLN were located only in the axillary region, but there were no other specific features in the location or size of SLN. The SLN were metastatic in 10 of the 25 patients: in 4, the SLN were the only metastatic nodes whereas in the remaining 6 patients, other axillary nodes were also positive. Fifteen patients with no metastasis in SLN had no tumor involvement in any other lymph nodes. There were no skip metastases.ConclusionSLN identified with labeled tin colloids have clinical value in predicting the metastatic status of the remaining axillary lymph nodes in breast cancer.

Effect of anastrozole and tamoxifen on lipid metabolism in Japanese postmenopausal women with early breast cancer.

Endocrine therapies that profoundly decrease estrogen levels potentially have a detrimental effect on the cardiovascular system. This study evaluated the effect on lipid metabolism of one such agent, the new generation aromatase inhibitor anastrozole, compared with tamoxifen, when used as adjuvant treatment in postmenopausal Japanese women with early breast cancer. All patients had completed primary surgery and were randomized to anastrozole 1 mg once daily (n=22) or tamoxifen 20 mg once daily (n=22). Anastrozole significantly reduced levels of triglycerides and remnant-like particle cholesterol, whereas tamoxifen significantly increased these. Activity of lipoprotein lipase and levels of high-density lipoprotein cholesterol significantly increased after anastrozole treatment. In contrast, activity of hepatic triglyceride lipase, also a key enzyme of triglyceride metabolism, significantly decreased following treatment with tamoxifen. We thus conclude that in our study anastrozole had a beneficial effect on lipid profiles of postmenopausal women with early breast cancer after 12 weeks of treatment.

Sentinel lymph node identification for patients with breast cancer using large-size radiotracer particles: technetium-99m-labeled tin colloids produced excellent results.

Sentinel lymph node (SLN) biopsies using radioactive tracers have been reported to detect the metastatic status of the axillary lymph nodes in breast cancer patients. However, the optimal radioactive tracer particle sizes remain to be determined. In this study, identification of SLNs with large radiolabeled tin colloid particles was evaluated. Seventy‐five patients with T1‐2, N0 breast cancer were enrolled. Two hours prior to surgery, 1 to 2.5 mL technetium‐99m–labeled tin colloid particles were injected around the tumor under ultrasonographic guidance. Immediately before the operation, dye fluids were also injected around the tumor to increase the interstitial pressure. After axillary dissection, lymph nodes with ×100 or more uptake of radioactivity than the mean of the other lymph nodes are considered to be SLN. All lymph nodes from the axillary dissections were pathologically investigated, and the characteristics of SLNs were evaluated. SLNs were clearly identified in 74 of 75 patients (98.7%). Of 37 patients without SLN metastasis, pathological investigation revealed no further involvement of the remaining non‐SLNs. The SLNs tended to be larger in size, and more than 50% were located in the lower medial site of the axilla. This is the first study to show that SLNs could successfully be identified with radiolabeled tin colloid particles. When SLNs were negative for metastases, non‐SLNs were always negative.

Indications and Technique of Sentinel Lymph Node Biopsy in Breast Cancer Using 99m-Technetium Labeled Tin Colloids

BackgroundThe status of the sentinel lymph node (SLN) can reflect the status of other lymph nodes in breast cancer. The efficacy of dye injection and radiolabeled tin colloids for the accurate identification of the SLN was investigated. The indications for SLN biopsy for determing clinical nodal status were also investigated.MethodsA total of 108 patients with breast cancers less than 5 cm were enrolled. Ninety-six patients were clinically node negative and 12 were node positive. About 2 hours before surgery, 1 to 2.5 ml of 99m-technetium-labeled tin colloid was injected around the tumor. Just before the operation, dye was also injected into the tissue surrounding the tumor. Six clinically node negative patients were omitted from the dye-injection process. The SLN was identified as a lymph node with extremely high radioactivity using a gamma probe or a gamma counter. Complete axillary dissection was performed and the metastatic status investigated by hematoxylin and eosin staining.ResultsIn clinically node negative patients undergoing dye-injection, the SLN was identified in 89 of 90 patients (98.9%), and there was only one patient with lymph node metastasis outside the SLN. However, in clinically node positive patients undergoing dye-injection, the identification rate of the SLN was 66.7% (8 of 12 patients) and there was one patient with lymph node metastasis outside the SLN (12.5%). Without dye-injection, the SLN could be detected in 4 of 6 patients (66.7%).ConclusionsSuccessful identification of the SLN with tin colloid requires concomitant dye-injection and candidates for SLN biopsy should be restricted to clinically node negative cases.

Optimal particle size of radiocolloid for sentinel node identification in breast cancer — Electron microscopic study and clinical comparison

BackgroundSentinel node (SN) biopsy using a radiotracer is easy to learn, reproducible, and performed by the majority of breast cancer surgeons. However, this technique raises the question: what is the optimal particle size of colloid?MethodsPatients were injected with conventional tin colloid (median particle diameter: 700 nm) and the predominant particle size of radiocolloid retained in the SN was measured using electron microscopy. This showed a narrow distribution of colloidal size (100–150 nm). Patients were then injected with modified tin colloid having a median particle size of 100 nm. A clinical comparison was performed between conventional particle size or reduced particle size tin colloid and the SN biopsy success rate, the number of SNs, and the colloidal uptake in SNs.ResultsA total of 118 patients were injected with the conventional tin colloid (group I) and 124 patients with the smaller particle colloid (group II). The identification rate and the number of SN in both groups were almost equal, and the patients with low-uptake SNs were not significantly less in group I (p = 0.55).However, in the subgroup of patients 60 years of age or more, group II had significantly more SNs than group I (1.4 vs 1.9;p = 0.03) and low-uptake SNs were significantly less common than in group I (0 = 0.02).ConclusionsThe improvement of colloidal uptake in SNs using the smaller particle size tin colloid was confirmed, and this impact was statistically significant in the older population.

Clinicopathologic and Technical Factors Associated with the Uptake of Radiocolloid by Sentinel Nodes in Patients with Breast Cancer

AbstractPurpose. Sentinel-node biopsy is becoming widely accepted in breast cancer treatment. Using the radioisotope technique, a lower risk of identification failure is related to the amount of radiocolloid in the sentinel nodes. The aim of this study was to identify the factors associated with the colloidal uptake of the sentinel nodes. Methods. Technetium-labeled colloid was injected peritumorally, with or without subdermal injection. According to the maximum radioactivity of the sentinel nodes, patients were divided into high (≥100 counts/s) or low (<100 counts/s) uptake groups. The uptake was compared in relation to the clinicopathologic and technical features. Results. The sentinel node was identified in 183 of 186 patients (98.4%), with 60 and 123 patients in the low- and high-uptake groups (mean: 39 and 1003 counts/s), respectively. Multivariate analysis showed that an age of 65 years or older and a sentinel-node size of 8 mm or more were significantly more predominant in the low-uptake group. Conclusion. Care must be taken when performing sentinel-node biopsy, especially for aged patients and for those with large sentinel nodes. The optimal technique should be determined on the basis of these results.

Trichoblastoma of the skin occurring in the breast. A case report.

BACKGROUND Trichoblastoma is a rare benign skin appendage tumor constituted mostly of follicular germinative cells. It can arise on any part of the body except the palms, soles, nail units and mucosal membranes. No case of it in breast skin has been reported before. Furthermore, fine needle aspiration cytology findings on this lesion have not been described before. CASE A 76-year-old female presented with a firm nodule in her left breast. The tumor was well demarcated, about 1.5 cm in diameter. Fine needle aspiration cytology revealed clusters composed of relatively uniform cells with a high nuclear/cytoplasmic ratio. In the midst of some clusters, the tumor cells had a more abundant cytoplasm. Fibrocellular interstitium or dense cyanophilic acellular material occasionally was attached to them. The tumor cells had oval or fusiform nuclei that had fine, evenly dispersed chromatin. To exclude a diagnosis of breast cancer, it is important to recognize that the clusters are composed of basaloid cells with focal squamous eddies and that there is at least focally peripheral palisading. The histopathologic diagnosis was trichoblastoma. CONCLUSION Fine needle aspiration cytology can distinguish trichoblastoma from malignant diseases of the breast and may be used to diagnose the lesion in conjunction with clinical findings.