Magnetic resonance imaging of breast cancer and correlation with prognostic factors.

BACKGROUND: Prognostic factors of breast cancer have been used for the prediction of clinical outcome or selection of patients for complementary treatment. Some of the imaging features of breast cancer, e.g. magnetic resonance imaging (MRI), are associated with these prognostic factors. PURPOSE: To evaluate the relationship between dynamic enhanced MR features and prognostic factors of clinical outcome of breast cancer. MATERIAL AND METHODS: A total of 136 patients with 151 breast cancers underwent 1.5T dynamic MR imaging with the use of a dynamic T1-weighted three-dimensional fast low-angle shot (FLASH) subtraction imaging technique. Morphological and kinetic analyses of MR features were evaluated using the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon. Pathological prognostic factors were correlated with MR imaging characteristics, including tumor size, histological grade, lymph node status, expression of estrogen receptor (ER), expression of progesterone receptor (PR), expression of c-erbB2, determination of Ki-67 index, and microvascular density (MVD), using univariate and multivariate statistical analyses. RESULTS: Based on univariate and multivariate analyses, spiculated tumor margins correlated significantly with lower histological grade (I-II) and positive PR expression. Rim enhancement was significantly correlated with high histological grade, presence of axillary lymph node metastasis, large tumor size, increased Ki-67 index, and increased MVD. Early peak enhancement, as seen on the first scan after contrast medium injection, was correlated with negative ER expression. CONCLUSION: The presence of a lesion with a spiculated margin may predict a relatively good prognosis, and the presence of a lesion with rim enhancement may predict a relatively poor prognosis.

Immunohistochemical study of mechanoreceptors in the tibial remnant of the ruptured anterior cruciate ligament in human knees.

This study was performed to identify the mechanoreceptors in the tibial remnants of ruptured human anterior cruciate ligaments (ACL) by immunohistochemical staining. Thirty-six specimens of tibial ACL remnants were obtained from patients with ACL ruptures during arthroscopic ACL reconstruction. As control, two normal ACL specimens were taken from healthy knee amputated at thigh level due to trauma. The specimen was serially sectioned at 40 mum. In control group, the average number of sections per specimen was 132, and a total of 264 slices were available. In remnant group, the average number of sections per specimen was 90, and a total of 3,251 slices were available. Immunohistochemical staining was performed to detect the neural element of mechanoreceptors. Histologic examinations were performed under a light microscope and interpreted by a pathologist. Nineteen (8 Ruffini, 11 Golgi) mechanoreceptors were identified in the two normal ACLs, which were evenly distributed at both tibial and femoral attachments. In the remnant group, mechanoreceptors were observed in 12 out of 36 cases (33%), and a total of 17 (6 Ruffini and 11 Golgi) mechanoreceptors observed. No significant differences in the harvest volume, number of sections, age, or time between injury to surgery was observed between the 12 mechanoreceptor-present and the 24 mechanoreceptor-absent ones. The presence of mechanoreceptor at the tibial remnants of torn ACLs was verified. The immunohistochemical staining methodology proved useful, but requires further refinement. Although the mechanoreceptors were detected relatively less frequently than expected, the authors consider that it does not negate the necessity of remnant-preserving ACL reconstruction.

Diagnostic algorithm for papillary urothelial tumors in the urinary bladder.

Papillary urothelial neoplasms with deceptively bland cytology cannot be easily classified. We aimed to design a new algorithm that could differentiate between these neoplasms based on a scoring system. We proposed a new scoring system that enables to reproducibly diagnose non-invasive papillary urothelial tumors. In this system, each lesion was given individual scores from 0 to 3 for mitosis and cellular thickness, from 0 to 2 for cellular atypia, and an additional score for papillary fusion. These scores were combined to form a summed score allowing the tumors to be ranked as follows: 0-1 = UP, 2-4 = low malignant potential (LMP), 5-7 = low-grade transitional cell carcinoma (TCC), and 8-9 = high-grade TCC. In addition to the scoring system, ancillary studies of MIB and p53 indexes with CK20 expression pattern analyses were compared together with clinical parameters. The MIB index was strongly correlated with disease progression. Four of the 22 LMP patients (18.2%) had late recurrences, two of these four (9.1%) had progression to low-grade carcinoma. The MIB index for LMP patients was strongly associated with recurrence (recurrence vs. non-recurrence, 16.5 vs. 8.1, p < 0.001). The proposed scoring system could enhance the reproducibility to distinguish papillary urothelial neoplasms.

Castleman's disease of the axilla mimicking metastasis.

Castleman's disease is an unusual inflammatory lymphoproliferative disorder of unknown cause. It most commonly occurs in the mediastinum but rarely in the axillary lymph nodes. We report a case of localized axillary Castleman's disease mimicking metastasis as the patient had a palpable malignant mass in the breast, described by ultrasonography, color Doppler ultrasonography, contrast-enhanced CT, and dynamic enhanced breast MR images.

Successful eradication of relapsed primary effusion lymphoma with high-dose chemotherapy and autologous stem cell transplantation in a patient seronegative for human immunodeficiency virus.

Primary effusion lymphoma (PEL) is a recently recognized disease that occurs most often in immunosuppressed patients, either with human immunodeficiency virus (HIV) or in the posttransplantation setting, and it occasionally occurs in nonimmunosuppressed patients. Patients present with lymphomatous effusions in serous cavities--pleura, pericardium, or peritoneum--without any identifiable tumor mass. PEL rarely responds to systemic chemotherapy, and the prognosis is poor, with a median survival time of less than 6 months for most cohorts. A standard treatment for PEL has not yet been identified. We describe a patient with HIV-seronegative PEL who relapsed after combination chemotherapy and then underwent successful treatment with high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). The treatment was well tolerated, and the patient has been in remission for 12 months after HDC and ASCT.

Isolation of endothelial progenitor cells from cord blood and induction of differentiation by ex vivo expansion.

Endothelial progenitor cells (EPCs) have been reported to possess the capacity to colonize vascular grafts and hold promise for therapeutic neovascularization. However, limited quantities of EPCs have been the major factor impeding effective research on vasculoangiogenesis. In this study, cytokine and culture conditions necessary for the provision of large quantities of endothelial cells (ECs) were investigated. Cord blood was collected from 18 normal full-term deliveries and CD34+ cells were isolated by MACS system (Miltenyi Biotech, Bergish-Gladbach, Germany). To evaluate the effect of cytokines, CD34+ cells were cultured with various cytokine combinations, such as stem cell factor (SCF), flt3-ligand (FL), and thrombopoietin (TPO) with vascular endothelial growth factor (VEGF), interleukin-1 beta , fibroblast growth factor-basic (FGF-b) as basic cytokines. The quantities of non-adherent and adherent cells were the greatest with SCF, FL and TPO. The addition of TPO to all other cytokines significantly increased the number of non-adherent and adherent cells (p< 0.05, Wilcoxon rank sum test). After four weeks of culture, adherent cells expressed endothelial specific markers such as KDR, CD31 and CD62E. Typical morphology of ECs was observed during culture, such as cord-like structure and cobblestone appearance, suggesting that the adherent cells were consistent with ECs. In this study, the experimental conditions that optimize the production of ECs for therapeutic neovascularization were described. And it was possibly suggested that TPO plays a major role in differentiation from EPCs to ECs.

Detection of the BCR-ABL gene by interphase fluorescence in situ hybridization (iFISH) in chronic myelogenous leukemia patients after hemopoietic stem cell transplantation: the feasibility of iFISH monitoring of therapeutic response in peripheral blood.

The detection of the Philadelphia (Ph) translocation has been accomplished primarily by cytogenetic analysis and reverse transcriptase polymerase chain reaction (RT-PCR). RT-PCR is highly sensitive (1/10(4)-10(6)) but not quantitatively reliable and is thus unsuitable for the monitoring of Ph-positive cells during therapy. Interphase fluorescence in situ hybridization (iFISH) allows analysis of a large number of cells (> 500) in a timely and efficiently quantitative manner. We obtained 118 peripheral blood (PB) and 127 bone marrow (BM) samples from 75 adult chronic myelogenous leukemia (CML) patients undergoing stem cell transplantation. We simultaneously performed nested RT-PCR and iFISH for all samples. False-positive cells were detected in 2.48% +/- 0.93% (mean +/- SD) of PB samples and 2.75% +/- 0.83% of BM samples. The iFISH results for PB and BM ranged from 1.4% to 92.8% and 1.0% to 93.8%, respectively. Correlation analysis of iFISH results for PB versus BM samples showed a strong relation (r = .993). A significant correlation (P < .05) was also found between iFISH and first-round RT-PCR. The sensitivity of BCR-ABL iFISH was similar to that of first-round RT-PCR, and iFISH results for PB and BM were also well correlated. Thus, iFISH analysis of PB and/or BM samples may be more clinically reliable than RT-PCR in the quantitative monitoring of BCR-ABL fusion in CML after transplantation.

Positive expression of insulin-like growth factor-1 receptor is associated with a positive hormone receptor status and a favorable prognosis in breast cancer.

PURPOSE: Insulin-like growth factor 1 receptor (IGF-1R) is commonly expressed in primary breast cancers. Understanding the role of IGF-1R signaling in the different subtypes of breast cancer is important because each subtype has a different outcome and requires different treatment modalities. However, the precise biological significance of IGF-1R expression in cancer cells is still unclear. In this study, we examined the expression of IGF-1R in the different molecular subtypes of breast cancer. The effects of IGF-1R expression on the survival rates and outcomes of breast cancer were also examined. METHODS: IGF-1R expression was evaluated immunohistochemically in tissue microarray blocks constructed from 1,198 invasive breast cancer samples collected from six medical institutions. IGF-1R expression was interpreted according to the human epidermal growth factor receptor 2 (HER2)/neu immunohistochemistry scoring system. Scores of 2+ and 3+ were considered positive. RESULTS: Positive IGF-1R expression was observed in 65.4% of invasive breast cancer samples. IGF-1R expression was detected in all cancer subtypes (luminal A, 84.4%; luminal B, 75.9%; HER2, 21.2%; triple-negative, 46.6%) and was found to be associated with a positive hormone receptor status and the absence of HER2 amplification (p<0.001). Positive IGF-1R expression was significantly associated with high survival rates (p=0.014). However, a multivariate analysis revealed that the expression levels of IGF-1R did not achieve statistical significance. In the triple-negative cancer subtype, IGF-1R expression was found to be associated with a lower disease-free survival rate (p=0.031). CONCLUSION: Positive IGF-1R expression is associated with a favorable prognosis in breast cancer. IGF-1R is frequently expressed in the luminal A/B subtypes of breast cancer, and its expression is related to the hormone receptor status.

A case of tuberculous prostatitis with abscess.

We present a case of acute prostatitis with abscess. The patient had undergone intravesical bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer. A prostate biopsy demonstrated tuberculous prostatitis with abscess. This case illustrates that when bladder cancer is treated with BCG, a tuberculous prostate abscess can develop.

Hormone receptor expression in invasive breast cancer among Korean women and comparison of 3 antiestrogen receptor antibodies: a multi-institutional retrospective study using tissue microarrays.

Estrogen receptor (ER) and progesterone receptor (PR) are prognostic markers of breast cancer and predictive markers of response to endocrine therapy. To determine rates of ER and PR expression in invasive breast carcinoma among Korean women, the Breast Pathology Study Group of the Korean Society of Pathologists collected 1198 specimens of invasive breast carcinoma from 6 university hospitals. Immunohistochemical analysis was carried out using 1 antibody against PR and 3 antibodies against ER (1D5, 6F11, and SP1). Specimens were evaluated using the semiquantitative Allred score (scores >2 were considered positive). A total of 1077 cases were interpretable for all 3 anti-ER antibodies. ER expression was positive in 68.5% of cases using SP1, in 59.6% using 1D5, and in 58.9% using 6F11. Of 1073 interpretable cases, PR expression was positive in 51.7% of cases. The frequency distribution of Allred scores revealed a bimodal pattern (complete absence of staining or staining in most cells) for both ER and PR. Patients with discordant results for 2 different ER antibodies showed a median overall survival (between that of double-positive cancer and that of double-negative cancer). Our results showed that the rate of hormone receptor expression in breast carcinomas among Korean patients did not differ from that of western patients. In addition, SP1 was the most sensitive antibody for identifying ER expression in tumors. However, further evaluation is needed to determine which antibody is the best for selecting patients with discordant results who are likely to respond to endocrine therapy.

HER2 Status by Standardized Immunohistochemistry and Silver-Enhanced In Situ Hybridization in Korean Breast Cancer.

PURPOSE: Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in 18% to 20% of breast cancers, and it is recognized as a prognostic and predictive marker. We investigated the HER2 status in Korean breast cancer by immunohistochemistry (IHC) and silver-enhanced in situ hybridization (SISH), as the first step toward building a nationwide quality assurance program for HER2 testing. METHODS: A total of 1,198 breast carcinoma samples were collected from six institutions and IHC and SISH were performed using tissue microarrays in central laboratories. The results were compared to those of local laboratories. RESULTS: Available data were obtained from 959 samples. Central IHC results were negative, equivocal, and positive for 756 (78.8%; range among institutions, 76.8-81.8%), 37 (3.9%; 1.9-6.2%), and 166 (17.3%; 13.6-20%), respectively. SISH results were negative, equivocal, and positive for 756 (78.8%; 77.4-79.9%), 2 (0.2%; 0-0.7%), and 201 (21%; 20.1-22.2%), respectively. HER2 gene amplification was observed in 4.4%, 19%, and 73.9% of the negative, equivocal and positive groups stratified by local IHC results, respectively. When central SISH was considered to be the gold standard method for measuring HER2 status, the false-negative and false-positive rates of local IHC were 14.4% (29/201) and 7.1% (54/756). The concordance rate between central IHC and SISH was 98.4%. CONCLUSION: Central IHC and SISH markedly decreased the interlaboratory variability of HER2 status and the results of the two were highly concordant. The quality control program for HER2 testing must be focused on decreasing both the false negativity and positivity of IHC in local laboratories.

Radiologic findings of mesothelioma at the tunica vaginalis.

Malignant mesothelioma of the tunica vaginalis testis is a rare, but often fatal, malignancy that usually appears during the fourth decade and has a strong relationship with occupational exposure to asbestos and long-lasting hydrocele. We present a case involving a 36-year-old man without a history of hydrocele, trauma, or exposure to asbestos who developed malignant mesothelioma.

A Case of Bladder Cancer Found during a Workup for Urge Incontinence.

Irritative urinary symptoms may suggest the possibility of bladder cancer. We report a case of metastatic bladder cancer that was discovered during a workup for urge incontinence in a 65-year-old woman with a history of stomach cancer. She had a medical history of gastrectomy due to stomach cancer 4 years previously. The patient complained of urgency unresponsive to anticholinergic therapy. Cystoscopy revealed the presence of suspicious bladder mucosal lesions that were biopsied. The pathology was consistent with metastatic signet-ring cell adenocarcinoma. This case suggests that irritative urinary symptoms can be the first clinical manifestation in patients with bladder cancer.

Synchronous bilateral mucinous carcinoma of the breast: case report.

A mucinous carcinoma of the breast is a well-differentiated rare histological type of invasive ductal carcinoma, having a lower frequency of metastasis to an axillary lymph node and a better survival rate. Bilateral breast cancer has an overall incidence of 4% to 20% in patients with primary operable breast cancer. Few reports exist in the clinical literature characterizing a synchronous bilateral mucinous carcinoma of the breast. We report the characteristic imaging findings of a bilateral mucinous carcinoma of the breast.

Comparative proteomics of pulmonary tumors with neuroendocrine differentiation.

We aimed to evaluate neuroendocrine pulmonary tumors (NEPT) by a novel method involving map tree construction by comparing all of the protein spots. We performed a proteomics analysis to assess the similarities in protein expression between neuroendocrine pulmonary tumors (NEPT), including typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC) and small cell carcinomas (SCLC). Total protein lysates were obtained from seven histologically confirmed frozen NEPT tissues, including 1TC, 2 SCLC, and 4 cases ranging from AC to LCNEC. 2-DE demonstrated that TC was similar to normal lung. AC, LCNEC, and SCLC were similar to each other, forming a group separate from TC, however, SCLC at an early stage showed a similarity to TC. MALDI analysis detected 9 surrogate endpoint biomarkers, including eIF5A1, GST M3, cytokeratin 18 (CK 18), FK506-binding protein p59, p63, MAGE-D2, mitochondrial short-chain enoyl-coenzyme A hydratase 1, tranferrin and poly (rC) binding protein 1. Immunohistochemical staining revealed a gradual decrease in expression rate of p63 and CK 18 with poor differentiation of NEPT. Our results demonstrate that (1) the comparative proteomics of NEPT match the WHO classification except for AC and LCNEC; (2) SCLC show differences in their proteomics according to tumor stage; and (3) CK 18 and p63 may be useful as diagnostically and prognostically available markers.

A comparison of five immunohistochemical biomarkers and HER-2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early-onset breast carcinoma.

BACKGROUND: The objective of this article was to compare five tumor markers between white women in the U.S. and native Korean women with early-onset breast carcinoma. METHODS: Sixty Korean women who were diagnosed with breast carcinoma at age 45 years or younger and 60 white women with breast carcinoma who were matched by age were selected for this study. The median age of both groups was 37 years. Paraffin embedded blocks of the primary tumor were processed for immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), p53, cyclin D1, and HER-2/neu. RESULTS: The proportion of tumors that stained positive for ER, PR, p53, and cyclin D1 in the Korean women were 47.5%, 42.4%, 28.8%, and 40.9%, respectively; in the white women, the proportions were 43.9%, 52.6%, 21.1%, and 59.1%, respectively. The differences between the white patients and the Korean patients were not statistically significant with respect to any of those variables. A significant difference was found in the expression of HER-2/neu. Specifically, positive HER-2/neu status was observed in 47.5% of Korean women, compared with overexpression in only 15.8% of white women (P < 0.001). Fluorescence in situ hybridization analysis for HER-2/neu gene amplification on all HER-2/neu positive samples that scored 2 + and 3 + demonstrated a significant difference (P = 0.007) in gene amplification between the two populations. Differences in HER-2/neu positivity were observed for the entire cohort as well as among the subsets of patients with negative and positive lymph node status. No association was found between immunoreactivity for the five markers and axillary lymph node metastasis. CONCLUSIONS: The findings of high positivity of HER-2/neu expression and gene amplification in Korean women with early-onset breast carcinoma may have potential implications for local and systemic management of breast carcinoma, especially anti-HER-2/neu therapy for patients with hormone receptor negativity. Further research will be needed to identify biologic and genetic factors and their effects on the survival between different racial groups.