A case report of pigmented mammary Paget's disease mimicking nevus of the nipple.

A 43-year-old Japanese woman consulted our hospital for a pigmented lesion on her right nipple. Two years later, the lesion became enlarged, measuring 5 × 5 mm. It was dark brown, had an irregular shape and relatively clear borders. Incisional biopsy yielded a pathological diagnosis of junctional nevus of the skin. An additional 2 years later, a small mass developed under the right nipple area and core needle biopsy yielded a pathologic diagnosis of invasive ductal carcinoma. Partial resection of the right EC areas included the skin of the nipple and sentinel lymph node biopsy was performed. Histologically, the skin of the nipple demonstrated small clusters of pigmented carcinoma cells that were low molecular weight cytokeratin (CAM5.2) positive. Most of the carcinoma cells were small and did not have abundant cytoplasm, but nuclear enlargement and prominent nucleoli indicated malignancy, and the cytoplasm was pale compared with that of the surrounding squamous epithelial cells. Scattered dendritic melanocytes were identified by S-100 protein and HMB-45 immunohistochemically. In the upper dermis, carcinoma cells also involved the lactiferous ducts. A small focus of carcinoma cells that invaded the fat tissues did not contain melanin pigment. The final diagnosis was pigmented mammary Paget's disease. Pigmented lesions on the nipple should be carefully examined, because pigmented mammary Paget's disease sometimes mimics malignant melanoma or junctional nevus.

Alteration of immunohistochemical biomarkers between pre- and post-chemotherapy: hormone receptors, HER2 and Ki-67.

The immunohistochemical (IHC) biomarkers of breast cancer, especially hormone receptors and HER2, are very important because the pharmacological therapeutic strategy is generally decided by biomarker expression patterns. Biomarkers are examined on pre-chemotherapeutic biopsy materials from patients in whom neoadjuvant chemotherapy is planned. Statistically significant changes between pre- and post-chemotherapeutic markers have been reported; however, the alterations in biomarkers are poorly understood. Fluctuation of the Ki-67 labeling index (LI) between pre- and post-neoadjuvant therapy is associated with chemotherapeutic effects and with the prognosis of patients. It has been shown that IHC evaluation of Ki-67 LI is useful as a predictive and a prognostic factor. There are issues to be considered surrounding the use of the IHC Ki-67 LI in routine practice, including the standardization of staining procedures and a cutoff point for Ki-67 LI detection. The current understanding of IHC evaluation of biomarkers for breast cancer under neoadjuvant chemotherapy is reviewed based on the literature.

Fine needle aspiration cytology of ductal adenoma of the breast with intracellular mucin: a report of three cases.

BACKGROUND: Ductal adenoma of the breast is a benign lesion that can mimic both the clinical and cytopathologic features of carcinoma. Benign breast lesions with intracellular mucin are extremely rare, and ductal adenoma with intracellular mucin has not previously been reported. Here we present three cases of ductal adenoma of the breast with foci of intracellular mucin. CASES: Three patients were admitted to Tokai University School of Medicine Hospital and underwent fine needle aspiration cytology and histologic examination by excisional biopsy or partial resection. Fine needle aspiration cytology was performed using a 23-gauge needle, and smears were immediately fixed in ethanol and stained as Papanicolaou preparations. Epithelial cells formed cohesive clusters, consisting of biphasic luminal and myoepithelial cells accompanied by apocrine metaplasia with occasional high nuclear atypia. All three cases showed intracellular mucin, in varying amounts, which led to their being overdiagnosed as malignant lesions. CONCLUSION: To avoid overdiagnosis of ductal adenomas as malignant lesions, it is important to recognize that both intracytoplasmic mucin and atypical apocrine features can be usual cytologic findings of this disease.

HER2 testing on core needle biopsy specimens from primary breast cancers: interobserver reproducibility and concordance with surgically resected specimens.

BACKGROUND: Accurate evaluation of human epidermal growth factor receptor type-2 (HER2) status based on core needle biopsy (CNB) specimens is mandatory for identification of patients with primary breast cancer who will benefit from primary systemic therapy with trastuzumab. The aim of the present study was to validate the application of HER2 testing with CNB specimens from primary breast cancers in terms of interobserver reproducibility and comparison with surgically resected specimens. METHODS: A total of 100 pairs of archival formalin-fixed paraffin-embedded CNB and surgically resected specimens of invasive breast carcinomas were cut into sections. All 100 paired sections were subjected to HER2 testing by immunohistochemistry (IHC) and 27 paired sections were subjected to that by fluorescence in situ hybridization (FISH), the results being evaluated by three and two observers, respectively. Interobserver agreement levels in terms of judgment and the concordance of consensus scores between CNB samples and the corresponding surgically resected specimens were estimated as the percentage agreement and κ statistic. RESULTS: In CNB specimens, the percentage interobserver agreement of HER2 scoring by IHC was 76% (κ = 0.71) for 3 × 3 categories (0-1+ versus 2+ versus 3+) and 90% (κ = 0.80) for 2 × 2 categories (0-2+ versus 3+). These levels were close to the corresponding ones for the surgically resected specimens: 80% (κ = 0.77) for 3 × 3 categories and 92% (κ = 0.88) for 2 × 2 categories. Concordance of consensus for HER2 scores determined by IHC between CNB and the corresponding surgical specimens was 87% (κ = 0.77) for 3 × 3 categories, and 94% (κ = 0.83) for 2 × 2 categories. Among the 13 tumors showing discordance in the mean IHC scores between the CNB and surgical specimens, the results of consensus for FISH results were concordant in 11. The rate of successful FISH analysis and the FISH positivity rate in cases with a HER2 IHC score of 2+ differed among specimens processed at different institutions. CONCLUSION: It is mandatory to study HER2 on breast cancers, and either CNB or surgical specimen can be used.

Somatostatin analogue inhibits the mobility of prostate carcinoma cells: a new therapeutic method for advanced prostate carcinoma.

The somatostatin analogue (SA) Octreotide has been used as a therapeutic reagent for somatostatin receptor type 2a (SSTR2a)-positive cancers. The purpose of this study is to detect SSTR2a in human prostate carcinomas and to elucidate the effects of SA on SSTR2a-positive prostate carcinoma cells to determine the potential of this drug as a new therapeutic method for advanced prostate carcinoma. Immunohistochemical study of SSTR2a was performed on 95 prostate carcinoma cases, and the results showed expression of SSTR2a in 14 of the 95 cases (14.74%); the histological grade (Gleason) and capsular invasion of the prostate carcinoma were directly related to SSTR2a expression. Among the ten cases of lymph node metastasis, SSTR2a expression was markedly higher. In vitro studies were performed using SSTR2a-positive prostate cancer cells, DU145 and PC3. Migration and invasion abilities of DU145 and PC3 cells were inhibited by SA in a dose-dependent manner. This inhibition was reversed by Rho-kinase inhibitor Y-27632. Morphological changes of the prostate cancer cells treated with SA and Y27632 corroborate the migration and invasion assays, although SA had no effect on proliferation of DU145 and PC3 cells. In conclusion, the somatostatin analogue may be beneficial for patients with advanced prostate carcinoma or to protect from distal metastasis if they are positive for SSTR2a.

Recommendations for 'adequate evaluation of hormone receptors' a report of the task force of the Japanese Breast Cancer Society.

The task force of the Japanese Breast Cancer Society was assembled to examine variable factors related to the immunohistochemical evaluation of hormone receptors in breast cancer, and to provide recommendations for adequate handling of specimens and accurate evaluations for hormone receptors. The various factors examined were: i) the adequate handling of breast cancer tissue for IHC, ii) the concordant rate between EIA and IHC assays using 5 different staining methods, iii) the inter-observer diversity for evaluation, and iv) the threshold for the predictive value of endocrine therapy of primary and recurrent/metastatic breast cancers. The conducted studies found that a 10% threshold was stable and reliable in spite of different validations including the concordance between IHC and EIA assays, inter-observer diversity and disease-free survival rates for patients who received tamoxifen for primary breast cancers. It was also found that 1% of threshold was useful in limited situations including the predictive value of endocrine therapy for recurrent/metastatic breast cancers. Based on these results for technical, pathological and clinical validation studies, a recommendation was proposed. Herein, we summarize the evidence, on which the recommendations were made, and customize the recommendations suitable for the current status.

Evaluation of HER2 gene amplification in invasive breast cancer using a dual-color chromogenic in situ hybridization (dual CISH).

Fluorescence in situ hybridization (FISH) assay is considered the 'gold standard' for evaluation of HER2/neu (HER2) gene status, however, it is difficult to recognize morphologic features of tumors using fluorescence microscopy. Thus, chromogenic in situ hybridization (CISH) has been proposed as an alternative method to evaluate HER2 gene amplification. Here, we examined the dual color CISH (dual CISH) method which provides information regarding the copy number of the HER2 gene and chromosome 17 centromere from a single slide. We examined 40 cases of invasive ductal carcinomas of the breast that were resected surgically. HER2 gene status was assessed with FISH (Abbott) and dual CISH (Dako). HER2 gene amplification status was classified according to the guidelines of the American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP). Comparison of the cut-off values for HER2/chromosome 17 centromere copy number ratio obtained by dual CISH and FISH showed that there was almost perfect agreement between two methods (Kappa coefficient 0.96). The results of the two commercial products were almost consistent for evaluation of HER2 gene counts on the sections. The current study proved that dual CISH is comparable with FISH for evaluating HER2 gene status.

High expression of thymidine phosphorylase in basal-like breast cancers: Stromal expression in EGFR- and/or CK5/6-positive breast cancers.

Expression of the estrogen receptor (ER), the progesterone receptor (PgR) or the human epidermal growth factor receptor-2 (HER2) in tumors is a good prognostic marker for breast cancer patients. However, approximately 15-20% of breast cancer patients have triple-negative breast cancer (TNBC; negative for ER, PgR and HER2), and efficient therapeutic modalities for these patients are under investigation. We focused on thymidine phosphorylase (TP), an enzyme metabolizing 5'-DFUR, an intermediate of capecitabine, to 5-fluorouracil in order to investigate the application of well-known therapeutics for TNBC. Results of a gene expression analysis showed that TP expression in TNBC and basal-like breast cancer (BLBC) was higher than that of other subtypes. Immunohistochemically, the high expression of TP in TNBC and BLBC reflected expression in stromal but not tumor cells. Notably, a high TP expression was observed in the stromal cells of EGFR- and/or CK5/6-positive breast tumors. Our present results showing a high expression of TP in BLBC indicate that capecitabine-based chemotherapy would be of benefit for patients with TNBC.

Breast conserving surgery for male noninvasive intracystic papillary carcinoma: a case report.

We report an exceedingly rare case of male breast cancer on two brothers. The patient has family history that his younger brother had breast cancer 5 years ago. The patient was 70-years old man who presented with chief complaint of an indolent tumor mass of the left breast. Mammography demonstrated a well defined mass with microcalcifications. Noninvasive intracystic papillary carcinoma was diagnosed by excisional biopsy. We performed breast conserving surgery (BCS) with sentinel lymph node biopsy for this patient. The histological diagnosis was same as above, with no metastasis of sentinel lymph node. Immunohistochemical study showed estrogen receptor (ER) and progesterone receptor (PgR) were positive respectively, and human epidermal growth factor receptor type 2 (HER2/c-erbB-2) was negative. After surgery, he underwent radiation therapy of 60 Gy for left chest wall include nipple and areolar area. We report the case of BCS for male breast cancer. The preservation of the nipple areolar complex in male patients may also have a positive psychological impact as is the case in women treated for breast cancer. Our patients report an outstanding cosmetic result. As for the man, breast conserving therapy should be enforced without overt nipple and areolar involvement like a woman.

Overexpression of fatty acid binding protein-7 correlates with basal-like subtype of breast cancer.

Fatty acid binding protein-7 (FABP-7) is normally expressed in the mammary gland. The aim of this study was to clarify the phenotype of breast cancers with respect to the overexpression of FABP-7. Reverse transcription PCR (RT-PCR) analysis was carried out on 16 cases, including 4 ER(+)/HER2(-), 2 ER(+)/HER2(+), 3 ER(-)/HER2(+), and 5 ER(-)/HER2(-) samples, and 2 non-neoplastic mammary glands as control tissue. Breast cancers categorized as ER(-)/HER2(-) revealed a high cDNA level of FABP-7 as compared to other groups of breast cancer (p=0.004). An immunohistochemical study carried out on 88 cases showed that FABP-7 overexpression had a strong relationship with triple-negative cases (45.8%, p=0.001) and the basal-like subtype (37.5%, p=0.001). Estrogen receptor (ER) and progesterone receptor (PgR) expressions had reverse correlation with FABP-7 overexpression (p=0.003, p<0.0001), but no significant associations can be identified between human epidermal growth factor receptor-2 (HER2) and FABP-7 (p=0.219). In conclusion, this study is the first to demonstrate overexpression of FABP-7 in triple-negative breast cancers [ER(-), PgR(-)/HER2(-)], especially in basal-like breast cancer, and to give a probable interpretation of the high histological grade and poor prognosis of basal-like breast cancer.

The role of trastuzumab in the management of HER2-positive metastatic breast cancer: an updated review.

Currently, trastuzumab is one of the key drugs in the treatment strategy for HER2-positive breast cancer. Although metastatic breast cancer is unlikely to be cured, some HER2-positive patients have survived for a long time with complete response to trastuzumab therapy. In HER2-positive metastatic breast cancer, single agent trastuzumab is effective and less toxic. Combination of trastuzumab with cytotoxic drugs is also effective. Therefore, major guidelines recommend using trastuzumab as a key drug in the management of HER2-positive metastatic breast cancer. However, many clinical questions still need to be solved. In this article, recent evidence was reviewed to find some answers about these issues.

A new reporting form for breast cytology.

The Cytology and Core Needle Biopsy Subcommittee, organized under the Rules Committee of the Japanese Breast Cancer Society, has prepared a new form for breast cytology reports. This reporting form consists of "diagnostic categories" and "recommendations." The "diagnostic category" is either "specimen inadequacy" or "specimen adequacy." The judgment on "specimen adequacy" is subdivided into four categories: "normal or benign," "indeterminate," "suspicious for malignancy," and "malignant." The "recommendation" indicates descriptions of cytological features and estimated histological type of tumor (these descriptions should be as detailed as possible). On the basis of an analysis of cytological data from 3,439 cases performed before preparing this form, the subcommittee has attached the following recommended goals to this form: (1) the percentage of "specimen inadequacy" should be 10% or less of all samples, (2) the percentage of "indeterminate" samples should be 10% or less of all "specimen adequacy" cases, and (3) 90% or more of "suspicious for malignancy" cases should be diagnosed as "malignant" in a subsequent histological examination. We hope that modification of this form, if it requires revision in the future, will be evidence-based, as was the process for compiling this set of rules.

Metastin inhibits migration and invasion of renal cell carcinoma with overexpression of metastin receptor.

BACKGROUND: Metastin, the final peptide of the KiSS-1 gene, has been proposed to suppress cell motility. OBJECTIVE: This study investigated whether renal cell carcinoma (RCC) tissue expresses metastin or its receptor, and clarified whether metastin can suppress migration and/or invasion and/or proliferation of RCC cells in vitro. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five RCC samples were submitted. Fresh RCC tissues were prepared for real-time RT-PCR, and formalin-fixed and paraffin-embedded tissues blocks were examined by immunohistochemistry. RCC cell lines Caki-1 and ACHN were supplied for cell migration, invasion, and proliferation assays. MEASUREMENTS: Real-time RT-PCR was performed by using Taq Man gene expression system. ENVISION system was used in immunohistochemistry. Wound-healing assay and matrigel assays were used to identify migration and invasion abilities of RCC cell lines. Cell Counting Kit-8 was applied to measure the cell proliferation. Cell morphology was examined under a META system. Statistical analysis was performed with SPSS15.0J. RESULTS AND LIMITATIONS: In twenty-five RCC samples, the mRNA level of metastin receptor was identified to be significantly higher than non-neoplastic renal cortex by real-time RT-PCR (p=0.011). Immunohistochemical study also detected metastin receptor protein in all RCC tumors. In vitro, this study showed that metastin inhibited migration and invasion of Caki-1 and ACHN cells. In contrast, it had no effects on cell proliferation. Metastin (10 micromol/l) induced excessive formation of focal adhesions and stress fibers in Caki-1 and ACHN cells; this phenomenon was inhibited by pretreating pharmacological Rho-kinase inhibitor (Y-27632) to those cells. CONCLUSION: This is the first report regarding overexpression of the metastin receptor hOT7T175 in human RCC. We demonstrate that metastin can inhibit migration and invasion of the RCC cell line, which is regulated by a Rho-kinase inhibitor. Metastin and its receptor are therefore probable targets for suppressing RCC.

What causes discrepancies in HER2 testing for breast cancer? A Japanese ring study in conjunction with the global standard.

We assessed interinstitutional and interobserver consistency of human epidermal growth factor receptor type-2 (HER2) testing using immunohistochemical analysis and fluorescence in situ hybridization (FISH) in a set of 20 breast cancer samples among 10 institutions in Japan and a Herceptin adjuvant study participating laboratory in Germany and identified factors that may lead to discordant results.We found a good agreement in immunohistochemical HER2 scoring between the coordinating institution and 10 participating laboratories (kappa = 0.718) and excellent agreement for FISH (kappa = 0.900). The results of a comparison between 10 Japanese laboratories and the German laboratory was good for immunohistochemical studies (kappa = 0.713) and excellent for FISH (kappa = 0.887). FISH retesting of equivocal samples (2+ immunohistochemically) improved agreement. Discrepancies between results were attributed to the evaluation process in 33.0% of the samples, staining procedures in 25.0%, and a combination of the two in 41.7%. Evaluation of samples according to the American Society of Clinical Oncology/College of American Pathologists guideline increased the number of 2+ immunohistochemical scores. By performing FISH retesting for these samples, consistency among multiple institutions could be archived. The quality of the staining procedures performed and the consistency of evaluations require regular assessment.

Cytological features of the cystic fluid of pancreatic schwannoma with cystic degeneration. A case report.

CONTEXT: Schwannomas are benign neoplasms arising from peripheral nerve tissue. Pancreatic schwannoma is a very rare condition. We present the histological and cytological features of a pancreatic schwannoma with cystic degeneration. CASE REPORT: A 51-year-old male was diagnosed with a cystic tumor measuring approximately 6 cm in the tail of the pancreas. Distal pancreatectomy and splenectomy were performed. Cystic fluid from the tumor was obtained intraoperatively by fine-needle aspiration, and it showed scattered spindle tumor cells against a background of hemosiderin-laden histiocytes. During the operation, we informed the surgeon that the tumor consisted of "atypical spindle cells". Histologically, the tumor was diagnosed as a schwannoma with cystic degeneration which had originated in the pancreas. The diagnosis was confirmed by positive immunostaining of the tumor cells in both histological and cytological materials for S-100 protein. CONCLUSION: Problems occasionally arise with the use of fine-needle aspiration in the diagnosis of cystic diseases of the pancreas because of the difficulty in obtaining adequate specimens. Nevertheless, it should be emphasized that intraoperative fine-needle aspiration is as informative as a frozen section diagnosis, when appropriately performed.

Lower HER-2/chromosome enumeration probe 17 ratio in cytologic HER-2 fluorescence in situ hybridization for breast cancers: three-dimensional analysis of intranuclear localization of centromere 17 and HER-2 signals.

BACKGROUND: Fluorescence in situ hybridization (FISH) is the gold standard for assessing HER-2 status for breast cancers, and paraffin-embedded tissue sections are used routinely for HER-2 FISH. Cytologic samples also are used, but to the authors' knowledge, little is known regarding the reliability of these samples. The objective of this study was to elucidate the usefulness of cytologic specimens for HER-2 FISH testing. METHODS: Histologic and cytologic specimens from 32 patients with invasive ductal carcinoma of the breast were subjected to comparative analysis of HER-2 status by FISH. FISH was performed by using a PathVysion HER-2 DNA Probe Kit according the manufacturer's instructions. The signal ratios of chromosome enumeration probe 17 (CEP17) and HER-2 were estimated and compared. In 15 cytologic specimens, the distance between signals (HER-2 and CEP17) and the nearest nuclear membrane were measured by using 3-dimensional image analysis and confocal microscopy. RESULTS: Cytologic and histologic FISH results were compared. Signal ratios of HER-2/CEP17 were lower in cytologic specimens from 26 of 32 patients compared with the histologic material. Three-dimensional image analysis demonstrated that the distance between the CEP17 signal and the nuclear membrane was shorter than the distance between the HER-2 gene and the nuclear membrane. CONCLUSIONS: The current results demonstrated that CEP17 could be lost more easily through histologic sectioning compared with the cytology results, because CEP17 is closer to the nuclear membrane. FISH analysis in cytologic specimens produced more accurate HER-2/CEP17 ratios, because the whole nucleus was subjected to FISH testing, compared with matched histologic specimens.

Ten cases of sebaceous carcinoma arising in nevus sebaceus.

Although nevus sebaceus is known to develop various types of secondary neoplasms, it rarely causes carcinoma and only 14 cases of secondary sebaceous carcinoma have been reported. In this study, 10 cases of sebaceous carcinoma arising in nevus sebaceus were collected. The clinicopathological features and results of immunohistochemical examinations with adipophilin, perilipin and p53 were summarized. Sebaceous carcinoma arising in nevus sebaceous predominantly occurred on the scalp (8/10) of elderly women (mean age, 67.7 years). No case was associated with Muir-Torre syndrome. We found several pathological features of sebaceous carcinoma; that is, made up mainly of germinative cells, moderate nuclear atypia without pleomorphism and many mitoses (4-28/10 high-power field). Adipophilin and perilipin antibodies highlighted lipid drops in the cytoplasm of the malignant cells in all cases. Overexpression of p53 was seen in all cases. In two cases there were coexisting benign-looking sebaceous lesions at the periphery of the main cancer nodule, and in these lesions p53 showed low positivity compared with the clearly malignant area. There was co-occurrence of another neoplasm in three cases with trichoblastoma, sebaceoma and syringocystadenoma papilliferum, respectively. All cases were treated by excision of the malignant lesion, with or without inclusion of the nevus sebaceus. In a follow-up period of 1-7 years, there was no case of recurrence, lymph node metastases or distant metastases. With these specific pathological and immunohistochemical findings using adipophilin, perilipin and p53, we have to consider the possibility that there is a tendency to underdiagnose secondary sebaceous carcinomas in nevus sebaceus. These clinicopathological features of sebaceous carcinomas developing in the nevus sebaceus seem to indicate different biological entities from de novo sebaceous carcinoma.

Assessment of a new anti-HER2 monoclonal antibody, SV2-61gamma: a best concordance with HER2 FISH.

It is critical to evaluate the overexpression of human epidermal growth factor receptor 2 (HER2) adequately in breast cancer cases. The aim of the present study is to assess the characteristics and usefulness of a novel monoclonal antibody, clone SV2-61gamma. The overexpression of HER2 was studied on paraffin sections of 50 breast cancers using a polyclonal antibody assay (HercepTest) and monoclonal antibodies (clones SV2-61gamma and CB11). Gene amplification of HER2 was determined by fluorescent in situ hybridization (FISH) using a HER2/CEP17DNA probe kit. Fifty tumors were scored as 0 (50.0%), 1+ (26.0%), 2+ (4.0%), or 3+ (20.0%) by immunohistochemistry using a monoclonal antibody, clone SV2-61gamma. The specificities of immunohistochemistry were 72.0% for the polyclonal antibody, 97.0% for SV2-61gamma, and 92.0% for CB11. The concordances with FISH were 78.0% for the polyclonal antibody, 98.0% for SV2-61gamma, and 94.0% for CB11. The positive predictive value of SV2-61gamma (92.0%) was higher than those of the polyclonal antibody (50.0%) and CB11 (79.0%). A monoclonal antibody clone SV2-61gamma showed very specific staining, with the best concordance with FISH, and it is useful for the evaluation of HER2 overexpression.

Increased phosphorylation of Akt in triple-negative breast cancers.

Cells from breast cancers lacking hormone receptors (estrogen receptor [ER], progesterone receptor [PgR]) and human epidermal growth factor receptor (HER) 2 strongly express the cell proliferation marker Ki-67. However, the mechanisms of and stimulus signals involved in cell proliferation of this type of breast cancer are not well understood. The aim of the present study was to examine the characteristics of signal transduction in triple-negative (ER-, PgR-, and HER2-negative) breast cancers. For 44 tumor samples, western blotting analysis was conducted to examine the phosphorylation of HER2, external signal-regulated kinase (ERK)1 and -2 and Akt, and the immunohistochemical phenotypes of the samples with respect to ER and HER2 were also assessed. Phosphorylation of HER2 was detected in 4 of 15 immunohistochemically HER2-positive tumor samples (26.7%). ERK1/2 was more highly phosphorylated in triple-negative breast cancers. Phosphorylation of Akt kinase was significantly higher in triple-negative breast cancers. Triple-negative breast cancers are characterized by increased phosphorylation of Akt kinase. In the present study, we found for the first time that there is a population with a significantly activated Akt pathway in this type of breast cancer.