Hisaki Fukushima

Immunohistochemical evaluation for hormone receptors in Breast Cancer: A practically useful evaluation system and handling protocol

This article reviews the current status of hormone receptor evaluation in and out of Japan, and introduces the proposed working protocol of the task force for Adequate immunohistochemical evaluation in routine practice for breast cancer by the Japanese Breast Cancer Society. Understanding the principles and the developmental process of immunohistochemisty helps us to utilize a scoring system adequately. Methodologies of hormone receptor examination and immunohistochemical procedures are briefly introduced. Each scoring system is based on different principles. The proposed working protocol takes into account the reproducibility of results among observers, institutions and staining procedures, which is justified based on the current situation in Japan. Future directions for the standardization of immunohistochemical hormone receptor evaluation are also described.

Comparison of Evaluations for Hormone Receptors in Breast Carcinoma Using Two Manual and Three Automated Immunohistochemical Assays

The aims of this study were to compare the quality of immunohistochemical assays of estrogen receptor (ER) and progesterone receptor (PR) and to compare the intermethod variability of assays from different manufacturers. immunohistochemical staining was entrusted to the following laboratories in Japan: Kyowa Medex, dealing with the products of BioGenex (Mishima, Shizuoka), DAKO Japan (Kyoto) and Ventana Japan (Yokohama). All slides were semiquantitatively evaluated according to the Allred score. Intermethod variability showed fair to moderate multirater kappa values for ER and PR (for total score, ER, kappa = 0.34; PR, kappa = 0.45). Another scoring system was also applied in which, irrespective of the intensity of nuclear staining, the proportion of cells stained in each specimen was recorded as 0; less than 1%; 1% or more and less than 10%; or 10% or more. Intermethod variability showed substantial multirater kappa values for ER and PR (according to percentage of positive cells, ER, kappa = 0.67; PR, kappa = 0.72). Concerning intermethod consistency, the scoring system based on the percentage of positive cells was advantageous over other scoring systems.

A case of dermatofibrosarcoma protuberans in the skin over the breast of a young woman

A 19-year-old woman with dermatofibrosarcoma protuberans (DFSP) of the breast is described. She presented with a tumor of the left breast with redness and swelling. She had noticed a small tumor five years previously, but it had begun to grow rapidly three months previously. Mammography, ultrasonography and aspiration biopsy cytology demonstrated an apparently benign tumor of the breast preoperatively. Wide excision was performed to confirm the diagnosis. Histologically, the tumor was composed of a uniform population of fibroblasts in a distinct storiform pattern. DFSP was diagnosed in the skin over the breast. This lesion ordinarily originates from the dermis in the trunk and proximal extremities. It is important to diagnose a soft tissue lesion accurately when it occurs in the breast.

Use of serial semithin frozen sections to evaluate the co-localization of estrogen receptors and progesterone receptors in cells of breast cancer tissues.

The extent of co-expression of estrogen receptors (ER) and progesterone receptors (PgR) in breast cancer cells was examined immunocytochemically. Eight surgical cases of infiltrating ductal carcinoma designated as ER-positive and PgR-positive (ER+/PgR+) by enzyme immunoassay (EIA) were used. They were fixed with 4% formaldehyde and cut into serial frozen semithin sections. Using sections stained with either anti-ER or anti-PgR antibody, we ascertained the co-localization of ER and PgR in a single cell and estimated the ratio of the number of cells co-expressing ER and PgR. Twenty-six to 95% of the cells were immunopositive for both ER and PgR, 2-25% of them, varying in cases, were positive for ER but not for PgR, and <3% of the cells were positive for PgR but not for ER. The remaining 5-60% cells were positive for neither ER nor PgR. A significant percentage of breast cancer cells in tissues designated as ER+/PgR+ by EIA showed the phenotype of ER-positive but PgR-negative. The co-expression ratio of ER and PgR in biochemically detected ER+/PgR+ breast cancer may reflect a particular clinical parameter, such as the heterogeneous responsiveness of ER+/PgR+ breast cancers to hormonal treatment. Immunostaining of serial semithin frozen sections for two or more different antigens is a useful method to assess the correlation of localization of antigens.

Mammary ductoscopy by helical CT: initial experience.

BackgroundAn attempt was made to visualize minute intraductal lesions using helical CT in patients with abnormal nipple discharge.MethodsGalactography was performed, immediately followed by CT (ductal CT examination). Based on the image data obtained, ductal images were constructed on a workstation using a Pegasus viewer (ductal CT imaging). Since no criteria for diagnosis by this method are available, ductal CT images were diagnosed by reference to the known ductal fiberscopic findings1,2).ResultsDuctal CT examination was performed in 10 cases, in 9 of whom ductal CT images were successfully constructed. Pathological examination was performed in 8 cases. It was possible to observe the structure of the luminal surface on the constructed ductoscopic images from all directions, but the color tone or the presence or absence of hemorrhage could not be observed.ConclusionsIn the examination for abnormal nipple discharge, ductal CT examination was useful for intraductal observation. Currently, it is a method that allows for observation of the most minute intraductal lesions. However, some issues still remain unresolved. The results of this study suggest that further studies with more cases hold the promise of making ductal CT imaging a useful examination method.BACKGROUND An attempt was made to visualize minute intraductal lesions using helical CT in patients with abnormal nipple discharge. METHODS Galactography was performed, immediately followed by CT (ductal CT examination). Based on the image data obtained, ductal images were constructed on a workstation using a Pegasus viewer (ductal CT imaging). Since no criteria for diagnosis by this method are available, ductal CT images were diagnosed by reference to the known ductal fiberscopic findings. RESULTS Ductal CT examination was performed in 10 cases, in 9 of whom ductal CT images were successfully constructed. Pathological examination was performed in 8 cases. It was possible to observe the structure of the luminal surface on the constructed ductoscopic images from all directions, but the color tone or the presence or absence of hemorrhage could not be observed. CONCLUSIONS In the examination for abnormal nipple discharge, ductal CT examination was useful for intraductal observation. Currently, it is a method that allows for observation of the most minute intraductal lesions. However, some issues still remain unresolved. The results of this study suggest that further studies with more cases hold the promise of making ductal CT imaging a useful examination method.

MR Imaging of the Breast : Current Status and Future Potential

1970年代後半に入ってから, 乳腺疾患に対しても応用され始めたMRIはMRI用造影剤 (Gd-DTPA) と高速撮像法を組み合わせたdynamic MRIの実現により, 病変の検出のみならず質的な診断能をも向上させた。最近の乳癌に対するMRIの診断成績をみると, sensitivityが100%との報告もあり, その完成度の高さを思わせる一方で, specificityに関しては37%ときわめて低いものから97%と高い報告もあり, 成績に大きな幅がある。このようにspecificityに大きな違いが生じる原因としては, 診断基準が定まっていないこと, sensitivityの向上に伴い乳癌とまぎらわしい良性腫瘤も多く検出されるようになったことなどが挙げられ, 診断基準の早期確立が望まれる。現在, MRIは乳腺腫瘤における良・悪性判別のための補助検査として, あるいは乳癌症例に対する術前検査に主として活用されているが, 乳癌治療の進歩に伴って流動していくものと考えられる。今後の課題としては, 癌の早期発見と治療を達成するためにspecificityの改善が挙げられ, MRIでのみ検出可能な腫瘤に対して将来的にはMRガイド下生検の必要性が高まってくるものと思われる。