Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype.

BACKGROUND: The aim of this study was to investigate the expression and clinical implications of proteins related to serine/glycine metabolism in different subtypes of thyroid cancer. METHODS: Tissue microarray (TMA) was constructed with tissues from 557 thyroid cancers, consisting of 244 papillary thyroid carcinomas (PTC), 112 follicular carcinomas (FC), 70 medullary carcinomas (MC), 23 poorly differentiated carcinomas (PDC), and 8 anaplastic carcinomas (AC). Immunohistochemical staining of the serine/glycine metabolism-related molecules phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase, (PSAT), phosphoserine phosphatase (PSPH), serine hydromethyl transferase (SHMT), and glycine decarboxylase (GLDC) was performed with the TMA blocks and the results were analyzed together with clinicopathologic parameters. RESULTS: The expression of serine/glycine metabolism-related proteins differed among thyroid cancer subtypes. The expression rate of PHGDH (p < 0.001), PSAT1 (p = 0.001), PSPH (p = 0.008), and tumoral SHMT1 (p < 0.001) was higher in PDC and PTC (78.3, 21.7, 21.7, 30.4 and 63.4, 18.6, 12.8, 31.4 %, respectively), and lowest in MC (15.7, 1.4, 0.0, 10.0 %). Stromal SHMT1 expression was highest in AC (62.5 %) and absent in all FC (p < 0.001). In PTC, positivity for PSPH (p = 0.041), tumoral SHMT1 (p = 0.018), and stromal SHMT1 (p < 0.001) expression was higher in the conventional type compared to follicular type (14.1 versus 2.5 %, 33.6 versus 15.0 %, 42.1 versus 10.0 %, respectively). BRAF V600E mutation was associated with a higher rate of PHGDH (p < 0.001), PSAT1 (p = 0.001), PSPH (p < 0.001), tumoral SHMT1 (p = 0.001), stromal SHMT1 (p < 0.001), and GLDC (p < 0.001) expression compared to non-mutant cases (73.5 versus 40.6 %, 23.1 versus 8.5 %, 17.6 versus 1.9 %, 37.0 versus 18.9 %, 45.8 versus 21.7 %, 21.8 versus 6.6 %, respectively). In univariate analysis, stromal SHMT1 expression was associated with shorter disease-free survival (p = 0.015) in follicular variant PTC, and GLDC positivity was associated with shorter overall survival (OS) in sclerotic stromal type (p = 0.002). In FC, minimally invasive type, PSPH positivity correlated with shorter OS (p = 0.045) and in MC, PHGDH positivity correlated with shorter OS (p = 0.034). CONCLUSION: The expression of serine/glycine metabolism-related proteins differs among different thyroid cancer types, with a higher rate of expression in PDC and PTC, and lower rate of expression in MC. In PTC, the rate of expression is lower in the follicular variant and higher in cases with BRAF V600E mutation.

Expression of cancer-associated fibroblast-related proteins in thyroid papillary carcinoma.

The purpose of this study was to evaluate the association between expression of cancer-associated fibroblast (CAF)-related proteins in papillary thyroid carcinoma (PTC) and clinicopathologic factors. Using tissue microarray (TMA) constructed from 339 cases of PTC (303 classic type, 36 follicular variant), we performed immunohistochemical staining for podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFRα, PDGFRß, NG2, 5-meC, and BRAF V600E and evaluated the association with clinicopathologic parameters. We classified the stroma of PTC as desmoplastic type, sclerotic type, pauci type, or inflammatory type. The expression of prolyl 4-hydroxylase (p = 0.042), FAPα (p = 0.044), PDGFRα (p < 0.001), and 5-meC (p = 0.030) in cancer cells differed according to the histologic subtype, higher in classic type than follicular type. The expression of FAPα (p = 0.034) and 5-meC (p = 0.021) in stromal cells was higher in the classic type than follicular type. PTC with BRAF mutation showed higher expression of podoplanin (p < 0.001), prolyl 4-hydroxylase (p = 0.013), FAPα (p < 0.001), S100A4 (p < 0.001), PDGFRα (p < 0.001), and 5-meC (p < 0.001) in the tumor cell compartment and of FAPα (p = 0.004), S100A4 (p < 0.001), PDGFRα (p = 0.002), PDGFRß (p < 0.001), and 5-meC (p < 0.001) in the stromal cell compartment. There was also a difference in the expression of CAF-related proteins according to stromal phenotype; the expression of FAPα, S100A4, and PDGFRα was higher in desmoplastic type than in other subtypes, whereas NG2 expression was higher in inflammatory type (p < 0.001). Tumoral podoplanin negativity (p = 0.043) was associated with shorter DFS, and tumoral S100A4 positivity (p = 0.044) and stromal PDGFRß positivity (p = 0.035) were associated with shorter OS. In conclusion, the expression of CAF-related proteins in cancer cells and stromal cells of PTC was different according to histologic subtype, BRAF V600E mutation, and subtype of stroma, and was related to prognosis.

Expression of autophagy-related markers beclin-1, light chain 3A, light chain 3B and p62 according to the molecular subtype of breast cancer.

AIMS: To investigate the relationship between the expression of autophagy-related proteins, including beclin-1, light chain (LC) 3A, LC3B, and p62, and prognosis in invasive breast cancer. METHODS AND RESULTS: We constructed tissue microarrays from the breast cancer cells of 489 patients, and classified molecular subtypes using surrogate immunohistochemical stains. The tumoral expression levels of LC3A and LC3B were highest in triple-negative breast cancer (TNBC) (P < 0.001), whereas these types of tumour had the lowest expression levels of these markers in the stroma (P = 0.005 and P < 0.001, respectively). Cytoplasmic beclin-1 expression was highest in TNBC, but nuclear expression was lowest (P < 0.001). p62 cytoplasmic and nuclear expression were highest in HER2-type tumours (P = 0.001 and P < 0.001, respectively). Tumoral LC3A and LC3B expression were associated with high histological grade (P < 0.001, and P < 0.028, respectively), but nuclear p62 expression was associated with lower histological grade (P = 0.004). CONCLUSIONS: Autophagy-related markers are differentially expressed according to the molecular subtype of breast cancer. In particular, expression of LC3A, LC3B and beclin-1 was highest in TNBC tumour cells, whereas that of LC3A and LC3B in the tumour stroma was lowest in TNBC.

The expression of metabolism-related proteins in phyllodes tumors.

The purpose of this study was to investigate the association between the expression of hypoxia-inducible factor (HIF)-1α, insulin-like growth factor (IGF)-1, glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX), and monocarboxylate transporter (MCT)4, which are metabolism-related proteins in phyllodes tumors (PTs), and clinicopathologic factors and its implication. We used tissue microarrays to analyze 207 PTs and performed immunohistochemical staining against the glycolysis-related molecules HIF-1α, IGF-1, Glut-1, CAIX, and MCT4. We then compared the immunohistochemical results and clinicopathologic parameters. The expressions of HIF-1α, Glut-1, CAIX, and MCT4 in the stromal component of PTs increased (P = 0.019, P < 0.001, P = 0.045, and P < 0.001, respectively) with increasing tumor grade. According to univariate analysis, factors associated with shorter disease-free survival were Glut-1 expression (P = 0.001) and MCT4 expression (P < 0.001) in the stromal component, and the factors associated with shorter overall survival were IGF-1 expression (P = 0.012), Glut-1 expression (P < 0.001), CAIX expression (P = 0.039), and MCT4 expression (P < 0.001) in the stromal component. Our investigation of stromal expression of the metabolism-related proteins HIF-1α, IGF-1, Glut-1, CAIX, and MCT4 revealed that, as the PT grade increased, the stromal expression of HIF-1α, Glut-1, CAIX, and MCT4 significantly increased. This result suggested that increasing PT grade is associated with increased glycolysis in the stromal component.

Metabolic phenotypes in triple-negative breast cancer.

The aim of study was to investigate the metabolism of tumor and stromal cells necessary to determine differential tumor-stroma metabolic interactions according to the molecular subtypes of triple-negative breast cancer (TNBC). Tissues from 132 patients of TNBC were prepared for use as tissue microarrays (TMA). Expression of CK5/6, EGFR, claudin 3, claudin 4, claudin7, E-cadherin, AR, GGT1, STAT1, and interleukin-8 was evaluated by immunohistochemical staining using TMA to classify molecular subtypes of TNBC. In addition, immunohistochemical staining for Glut1, CAIX, BNIP3, MCT4, Beclin-1, LC3A, LC3B, and p62 was performed. According to glycolytic status determined by the immunohistochemical expression of Glut-1 and CAIX in tumor and stroma, the metabolic phenotypes of the TNBCs were defined as follows: Warburg type (tumor: glycolysis, stroma: non-glycolysis), reverse Warburg type (tumor: non-glycolysis, stroma: glycolysis), mixed metabolic type (tumor: glycolysis, stroma: glycolysis), and metabolic null type (tumor: non-glycolysis, stroma: non-glycolysis). TNBCs were classified as follows: 79 Warburg type (59.8 %), 7 reverse Warburg type (5.3 %), 24 mixed metabolic type (18.2 %), and 22 metabolic null type (16.7 %). There was no statistical significance between the metabolic phenotypes and molecular subtypes (P=0.706). Reverse Warburg type showed the most dysfunctional mitochondrial status for stromal cells, while Warburg type showed the most functional mitochondrial status (P=0.036). Regarding stromal autophagy status, reverse Warburg type showed the most activated status, while all of the Warburg and metabolic null types showed a non-activated status (P<0.001). In conclusion, Warburg type was the most common metabolic phenotype in TNBC, while reverse Warburg type was the most unusual. Metabolic phenotypes did not differ among the molecular subtypes of TNBCs.

Metabolism-related proteins are differentially expressed according to the molecular subtype of invasive breast cancer defined by surrogate immunohistochemistry.

OBJECTIVE: The purpose of this study was to investigate the expression of metabolism-related proteins such as Glut-1 and carbonic anhydrase IX (CAIX) according to breast cancer molecular subtype. METHODS: We generated a tissue microarray of 276 breast cancer patients and performed immunohistochemical staining for known metabolism-related proteins, which were evaluated according to the molecular subtype. RESULTS: The expression of IGF-1, MIF, and HIF-1α was correlated with the HER-2 type (p < 0.05). Glut-1 overexpression and CAIX expression were associated with TNBC type, especially with basal-like type, high histologic grade, estrogen receptor negativity, and progesterone receptor negativity (p < 0.05). The expression of Glut-1 and CAIX was correlated with statistical significance (p < 0.001). CONCLUSION: We identified different patterns of expression of metabolism-related proteins according to the molecular subtypes of breast cancer defined by surrogate immunohistochemistry. Increased expression of HIF-1α, IGF-1, and MIF was noted in HER-2 type breast cancer and increased expression of Glut-1 and CAIX was noted in TNBC type breast cancer, especially in the basal-like subtype, which exhibited a glycolytic and acid-resistant tumor phenotype.

Molecules involved in epithelial-mesenchymal transition and epithelial-stromal interaction in phyllodes tumors: implications for histologic grade and prognosis.

The aim of this study was to investigate the expression of molecules associated with epithelial-mesenchymal transition (EMT) and epithelial-stromal interactions (ESI) and to evaluate their roles in phyllodes tumors (PTs). Tissue microarrays (TMAs) were constructed from 207 PT specimens (157 benign, 34 borderline and 16 malignant). The presence of EMT-related markers including N-cadherin, Twist, TGF-beta, HMGA2, S100A4 and Ezrin as well as ESI-related molecules such as SDF1 and CXCR4 among the TMAs was assessed immunohistochemically. Immunohistochemical results were analyzed in terms of clinicopathologic parameters. For higher grade PTs, expressions of Twist (p < 0.001), HMGA2 (p = 0.005), S100A4 (p < 0.001), CXCR4 (p < 0.001) and TGF-beta (p < 0.001) were higher. As PTs showed higher stromal cellularity, higher stromal mitosis, stromal overgrowth and infiltrative tumor margin, the expressions of Twist, HMGA2 and CXCR4 in the stromal component thereof were increased (p < 0.05). High Twist expression in the stromal component was associated with shorter disease-free survival (DFS) and overall survival (OS) (p < 0.001) as well as shorter OS in multivariate COX analysis (p = 0.031, odds ratio: 24.6). In conclusion, the expressions of Twist, HMGA2, TGF-beta and S100A4, which are EMT-associated molecules, and CXCR4, an ESI-associated molecule, were increased in the stromal component of advanced grade PTs. Further, high expression of Twist in the stromal component was correlated with poorer prognoses.

Expression of MUC1, MUC2, MUC5AC and MUC5B in mucinous lesions of the breast.

OBJECTIVE: The purpose of this study was to investigate the expression of MUC1, MUC2, MUC5AC and MUC5B in breast mucinous lesions. METHODS: Immunohistochemical staining of MUC1, MUC2, MUC5AC, MUC5B and synaptophysin was performed in 78 cases of mucinous carcinoma (MC), 36 cases of mucocele-like lesions (MLL) and 13 cases of solid papillary carcinoma (SPC). MC was classified as type A or type B and MLL was classified as MLL, MLL with atypical ductal hyperplasia and MLL with ductal carcinoma in situ. RESULTS: MUC1 was expressed in MC type A and MLL with luminal/apical pattern, while MC type B and SPC showed membrano-cytoplasmic expression of MUC1 (p < 0.001). A luminal/apical or luminal/apical + cytoplasmic pattern of MUC2 expression was observed in MC type A, while MC type B and SPC showed membrano-cytoplasmic MUC2 expression (p < 0.001). On MUC5B staining, MC type A and MLL were negative, while MC type B and SPC showed membrano-cytoplasmic expression (p = 0.011). The positive rate for synaptophysin was higher in MC type B and SPC than in MLL and MC type A (p = 0.001). CONCLUSIONS: Similar MUC phenotypes were observed between MLL and MC type A and between MC type B and SPC.

The expression of ERCC1, RRM1, and BRCA1 in breast cancer according to the immunohistochemical phenotypes.

We studied the expression of BRCA1, ERCC1, and RRM1 which play an important role in DNA repair systems in breast cancer. Immunohistochemical staining for EGFR, BRCA1, ERCC1, and RRM1 were performed by using a tissue microarray made from 230 breast cancer patients. Patients were classified into luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) types according to ER, PR, and HER-2 expression. The expression of ERCC1, RRM1, and BRCA1 were correlated (P < 0.05). The expression level of ERCC1 was the lowest in TNBC type (P = 0.031), ERCC1 negativity was more prominent in TNBC and luminal B groups than luminal A and HER-2 groups (P = 0.013). Cases with EGFR overexpression showed high expression of RRM1 and BRCA1 (P = 0.046, and 0.004, respectively). In conclusion, the expression of ERCC1 is particularly lower in TNBCs than other types of breast cancers.

Evaluation of intratumoral HER-2 heterogeneity by fluorescence in situ hybridization in invasive breast cancer: a single institution study.

This study aimed to determine the incidence and characteristics of HER-2 gene heterogeneity in invasive breast cancer in a single institution. Included were 971 cases of primary invasive breast cancer diagnosed between 2008 and 2010. Fluorescence in situ hybridization (FISH) image files were retrospectively reviewed and HER-2 gene heterogeneity was defined as more than 5% but less than 50% of analyzed invasive tumor cells with a HER-2/Chr17 ratio higher than 2.2, according to the College of American Pathologists guidelines. HER-2 gene heterogeneity was identified in 24 (2.5%) cases. The mean proportion of invasive tumor cells with a HER-2/chromosome 17 ratio higher than 2.2 was 11.6% (range: 5%-25%). Of 24 cases, HER-2 gene status was not amplified in 8, showed borderline amplification in 2, and amplification in 14. All HER-2 amplification cases were low-grade. In conclusion, HER-2 gene heterogeneity of invasive breast cancer is identified in routine FISH examination. This may affect the results of HER-2 gene amplification status in FISH studies.

Cytologic characteristics and ß-catenin immunocytochemistry on smear slide of cribriform-morular variant of papillary thyroid carcinoma.

OBJECTIVE: The purpose of this study is to analyze the characteristic cytologic features of the cribriform-morular variant of papillary thyroid carcinoma (CVPTC) and to find out the possibility of a preoperative diagnosis of CVPTC in fine needle aspiration (FNA). STUDY DESIGN: A retrospective review of cytologic features of 5 patients who were diagnosed with CVPTC after thyroidectomy and underwent preoperative FNA was performed. In addition, ß-catenin immunocytochemistry on a smear slide was applied. RESULTS: All cases showed a high cellularity smear, cribriform architecture, ovoid/columnar cells, obvious nucleoli, and nuclear groove. Epithelial morules were observed in 4 (80%) cases. All cases demonstrated a nuclear and cytoplasmic expression in ß-catenin immunocytochemistry applied to a smear slide. CONCLUSION: Preoperative diagnosis of CVPTC can be made by cytologic features of cribriform architecture, epithelial morule, and columnar cells in FNA and ß-catenin immunocytochemistry on a smear slide showing a nuclear and cytoplasm expression.

Alteration of REDD1-mediated mammalian target of rapamycin pathway and hypoxia-inducible factor-1α regulation in human breast cancer.

OBJECTIVE: The purpose of this study is to investigate REDD1-(regulated in development and DNA damage response 1) mediated regulation of the mammalian target of rapamycin (mTOR) pathway in breast cancer. METHODS: A tissue microarray included samples from 224 patients with breast cancer, and 30 patients with papilloma were used as a control group. An immunohistochemistry (IHC) including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epithelial growth factor receptor, cytokeratin 5/6, glucose transporter 1 (Glut-1), hypoxia-inducible factor (HIF)-1α, REDD1, AMPK (5'-adenosine-monophosphate-activated protein kinase) α(1), 14-3-3σ, phosphatase and tensin homolog, phospho-Akt, phospho-mTOR, phospho-S6, and Ki-67 was conducted. The phenotypic classification of breast cancer was performed based on the results of the IHC for ER, PR and HER2: luminal A, luminal B, HER2 overexpression and triple-negative breast cancer (TNBC). RESULTS: Glut-1 and HIF-1α were more highly expressed in TNBC, the HER2 overexpression type and papilloma than in the luminal A and B phenotypes (p = 0.000). REDD1 expression was higher in papilloma than in breast cancer (p = 0.000), but no difference was found among the 4 breast cancer phenotypes (p = 0.307). CONCLUSION: In the HER2 overexpression type and TNBC, tumor cell proliferation and survival in the hypoxic tumor environment could possibly be due to disinhibition of the mTOR pathway and HIF-1α stabilization by downregulation of REDD1.

Metastatic breast cancer shows different immunohistochemical phenotype according to metastatic site.

AIMS AND BACKGROUND: The study was performed to assess the status of immunohistochemical markers in primary and metastatic breast cancer and to determine the organ-specific characteristics of metastatic breast cancer. METHODS: Samples from 13 cases of paired primary and metastatic breast cancer and 34 cases of metastatic breast cancer were included. RESULTS: In the analysis of 13 cases of paired primary and metastatic breast cancer, estrogen receptor and progesterone receptor loss were noted in 1 (7.7%) case each. Androgen receptor loss and gain was noted in 2 (15.4%) cases, respectively. HER-2 showed 100% concordance with primary and metastatic tumors. C-kit was demonstrated in only 2 (15.4%) cases of metastatic breast cancer. In the analysis of 34 cases of metastatic breast cancer, when classified into triple-negative type (ER-, PR-, and HER-2-), HER-2+ type, and ER+ or PR+/HER-2- type according to immunohistochemical stain results, HER-2 type (66.7%) in brain metastasis and ER+ or PR+/HER-2- type (75.0%) in liver metastasis were predominant. Bone metastasis was composed of triple negative type (44.4%) and ER+ or PR+/HER-2- type (55.6%), and lung metastasis showed all of three subtypes in similar proportions. CONCLUSIONS: Metastatic breast cancer shows different immunohistochemical phenotypes according to metastatic site (P = 0.048).

Importance of foamy macrophages only in fine needle aspirates to cytologic diagnostic accuracy of cystic metastatic papillary thyroid carcinoma.

OBJECTIVE: To investigate the important cytologic features and thyroglobulin (Tg) level in fine needle aspiration cytology (FNAC) of cystic metastasis of papillary thyroid carcinoma (PTC) and to find some independent cytologic factors that enhance the diagnostic accuracy of cystic lymph node metastasis without identifiable tumor cells or high levels of Tg. STUDY DESIGN: Two hundred forty-four aspiration cytology cases with correspondent tissue specimens were included in the study. Cytologic features and FNAC Tg level were evaluated in each case. RESULTS: Twelve cases showed cystic lymph node metastasis in tissue slides but negative cytology with a mean FNAC Tg level of 413.3 ng/mL (range, 71.9-963.0). Out of these, 10 cases (83.3%) demonstrated only foamy macrophages. CONCLUSION: Foamy macrophages only without Tg level information in FNAC could raise the possibility of cystic metastatic PTC even if no identifiable tumor cells are found.

The predictive role of E-cadherin and androgen receptor on in vitro chemosensitivity in triple-negative breast Cancer.

OBJECTIVE: The purpose of this study was to evaluate the impact of various pathologic and biologic factors in triple-negative breast cancer (TNBC) on chemotherapy response using in vitro ATP-based chemotherapy response assay (ATP-CRA). METHODS: Forty-seven cases of TNBC were included. Immunohistochemical stains for androgen receptor (AR), p53, CD10, c-kit, CK5/6, vimentin, bcl-2, E-cadherin, Ki-67 and epidermal growth factor receptor were performed. In vitro ATP-CRA was used to analyze chemosensitivity for 5-fluorouracil (5-FU), docetaxel, doxorubicin, epirubicin, vinorelbine, gemcitabine, methotrexate (MTX), oxaliplatin and paclitaxel. RESULTS: The results showed that all cytotoxic agents demonstrated the trend that E-cadherin-expressing cases had a higher cell death rate than E-cadherin-negative cases. Particularly, vinorelbine showed statistical significance (P = 0.004). Cases with AR expression showed higher cell death rates than those without in 5-FU and MTX (P = 0.012 and 0.014, respectively). CONCLUSIONS: E-cadherin and AR could be candidate predictive factors for chemotherapy response in TNBC. Further in vivo study is required to clarify their roles.

Xanthogranulomatous mastitis: clinicopathology and pathological implications.

Xanthogranulomatous inflammation is an uncommon finding in the breast. Sixteen cases of xanthogranulomatous mastitis were reviewed to determine the characteristic clinicopathological features. Xanthogranulomatous mastitis involved foamy histiocyte clusters interspersed with inflammatory cells. Foamy histiocytes were bland with small pyknotic nuclei. Xanthogranulomatous mastitis was associated with fat necrosis in five cases (31%), multinucleated giant-cell reactions in six cases (38%), and cholesterol crystals in five cases (31%). In three cases (19%), xanthogranulomatous mastitis coincided with ductal carcinoma in situ or invasive ductal carcinoma. Duct ectasia with foamy histiocyte aggregates were noted in five cases (31%). It is suggested that the etiology of xanthogranulomatous mastitis is obstruction and rupture of the ectatic duct with foamy histiocyte aggregates. In breast core biopsy, granular cell tumor and invasive carcinoma such as histiocytoid carcinoma and lipid-rich carcinoma could demonstrate similar pathological features to xanthogranulomatous mastitis. In conclusion, xanthogranulomatous mastitis could be encountered in breast core biopsy and surgical excision tissue. Diagnosis of xanthogranulomatous mastitis can be made by excluding other diseases that elicit xanthogranulomatous inflammation in the breast. In breast core biopsy, xanthogranulomatous mastitis could be distinguished from granular cell tumor, histiocytoid carcinoma and lipid-rich carcinoma by using cytokeratin and histiocytic marker such as alpha1-anti-trypsin and CD68 stain.

Impact of grade, hormone receptor, and HER-2 status in women with breast cancer on response to specific chemotherapeutic agents by in vitro adenosine triphosphate-based chemotherapy response assay.

This study was designed to assess whether histological and biological factors of breast cancer can predict chemoresponse to specific agents. Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was employed to retrieve chemoresponse to 5-fluorouracil (5-FU), doxetaxel, doxorubicin, epirubicin, and paclitaxel in 49 patients. Tumors with high histologic and nuclear grade have higher response rate to doxorubicin (P<0.05) and palitaxel (P<0.05). Estrogen receptor (ER)-negative tumors respond well to doxorubicin (P=0.038), and progesterone receptor (PR)-negative tumors to 5-FU (P=0.039), doxetaxel (P=0.038), doxorubicin (P=0.000), epirubicin (P=0.010), and paclitaxel (P=0.003). Among the breast cancer subtypes determined by ER, PR, and HER-2 immunohistochemical stains, the HER-2+/ER- subtype has a higher response rate to doxorubicin (P=0.008). This in vitro result suggests that the combination of histologic and nuclear grade, hormone receptor, and HER-2 status can be a predictive factor of response to specific chemotherapy agents. Further in vivo study should be followed for clinical trials.

Intracranial dural metastasis of Ewing's sarcoma: a case report.

Although intracranial dural metastasis of Ewing's sarcoma is a very rare finding, its imaging characteristics are similar to those of its primary form in the central nervous system. Thus, this tumor must be considered in the differential diagnosis of extra-axial dural masses.

Metaplastic carcinoma with extensive chondroid differentiation in the breast (chondroid carcinoma).

Metaplastic breast carcinoma is very rare, and metaplastic carcinoma with chondroid differentiation is even rarer. Here, we report a case of metaplastic carcinoma with extensive chondroid differentiation mimicking chondrosarcoma that was challenging to diagnose. The tumor was characterized by an abundant chondromyxoid matrix. The definitive area of classic invasive ductal carcinoma was minimal. The peripheral portion of the tumor showed increased cellularity with pleomorphism and definitive invasive growth. Tumor cells in the chondrosarcomatous areas were diffusely immunoreactive for S-100 protein, patchy positive for cytokeratin, but negative for epithelial membrane antigen (EMA). Tumor cells in carcinomatous areas were diffusely positive for cytokeratin, S-100 protein, and patchy positive for EMA. In both areas, tumor cells were negative for smooth muscle actin (SMA) and CD34, while oncoprotein p53 was overexpressed. When pathologists encounter breast tumors with chondroid differentiation, careful sampling and immunohistochemistry for cytokeratin and SMA are most helpful to differentiate metaplastic carcinoma from malignant phyllodes tumor and malignant adenomyoepithelioma.

Pathologic Evaluation of Breast Cancer after Neoadjuvant Therapy.

Breast cancer, one of the most common cancers in women, has various treatment modalities. Neoadjuvant therapy (NAT) has been used in many clinical trials because it is easy to evaluate the treatment response to therapeutic agents in a short time period; consequently, NAT is currently a standard treatment modality for large-sized and locally advanced breast cancers, and its use in early-stage breast cancer is becoming more common. Thus, chances to encounter breast tissue from patients treated with NAT is increasing. However, systems for handling and evaluating such specimens have not been established. Several evaluation systems emphasize a multidisciplinary approach to increase the accuracy of breast cancer assessment. Thus, detailed and systematic evaluation of clinical, radiologic, and pathologic findings is important. In this review, we compare the major problems of each evaluation system and discuss important points for handling and evaluating NAT-treated breast specimens.