Eun Yoon Cho

Immunohistochemical study of the expression of adhesion molecules in ovarian serous neoplasms.

To clarify possible roles of adhesion molecules including E‐cadherin, β‐ and γ‐catenin, CD44s, CD44v6, CD56, and CD99 in ovarian serous neoplasms, an immunohistochemical study was undertaken for 23 benign, 40 borderline, and 95 malignant ovarian serous neoplasms using tissue microarray (TMA). Significantly reduced expression of E‐cadherin, and overexpression of CD44s, CD56, and CD99 were more frequently observed in adenocarcinomas than in benign and borderline tumors. Expression of CD44v6 and nuclear β‐ and γ‐catenin were detected only in borderline tumors and adenocarcinomas. Reduced expression of E‐cadherin was also correlated with high tumor grade (P = 0.03), presence of peritoneal seeding (P = 0.03), and low overall survival rate (P = 0.02). Overexpression of CD44s was significantly associated with high tumor grade (P = 0.04), advanced stage (P = 0.03), and low overall survival rate (P = 0.02). CD56 was increasingly expressed in the case of advanced stage (P = 0.005) and peritoneal seeding (P = 0.001). Nuclear staining for γ‐catenin was correlated with tumor progression (P = 0.004) and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.02). Only CD44s expression and stage were correlated with overall survival in multivariate study. These results suggest that although E‐cadherin, CD44s, CD56, and nuclear γ‐catenin immunoexpression seem to be useful prognostic markers for serous neoplasm of the ovary, CD44s expression and FIGO stage are independent prognostic factors.

Treatment outcomes and clinicopathologic characteristics of triple-negative breast cancer patients who received platinum-containing chemotherapy.

The aim of this study was to evaluate the role of platinum‐containing chemotherapy for metastatic triple‐negative breast cancer (TNBC) patients in terms of the response rate (RR) and progression‐free survival. A second aim was to characterize the clinical behavior at the time of relapse of TNBC. We retrospectively analyzed the clinical outcomes of patients with metastatic breast cancer who received taxane–platinum chemotherapy as the first‐ or second‐line treatment, focusing on the TN phenotype. In total, 257 patients with metastatic breast cancer received platinum‐containing chemotherapy at Samsung Medical Center from 1999 to 2006. Of these patients, 106 patients with available data on estrogen (ER), progesterone (PgR) and human epidermal growth factor receptor‐2 (HER2) receptor status received taxane–platinum regimen as the first‐ or second‐line treatment. The overall RR of patients with TNBC was 39%. This rate did not differ significantly from those of patients with other phenotypes. The time to death after chemotherapy (19 vs. 50 months, p = 0.037) and overall survival (OS) (21 vs. 56 months, p = 0.030) differed significantly between patients with TNBC and non‐TNBC. TNBC showed a unique locoregional infiltration pattern at relapse, which might reflect its aggressive clinical behavior. Despite the similar response to platinum‐containing chemotherapy, patients with TNBC had a shorter OS than patients with non‐TNBC. The implication of TN phenotype as poor prognostic factor is uncertain, because it needs to be defined whether poor outcome is related to the rapid growing characteristics of tumor itself or the resistance to drug therapy. Further prospective studies are warranted.

Characteristics of metastasis in the breast from extramammary malignancies

Breast metastasis from extramammary neoplasm is rare. We present the cases of metastasis to the breast after review of results in one institute and we want to show the difference of previous report.

Triple-negative, basal-like, and quintuple-negative breast cancers: better prediction model for survival

BackgroundTriple-negative breast cancers (TNBCs) and basal-like breast cancers (BLBCs) are known as poor outcome subtypes with a lack of targeted therapy. Previous studies have shown conflicting results regarding the difference of prognostic significance between TNBCs and BLBCs. In this study, we aimed to characterize the prognostic features of TNBCs, in view of BLBCs and quintuple-negative breast cancers (QNBC/5NPs).MethodsUsing tissue microarray-based immunohistochemical analysis, we categorized 951 primary breast cancers into four or five subtypes according to the expression of ER, PR, HER2, and basal markers (CK5/6, EGFR).ResultsThe results of this study showed that both TNBCs and BLBCs were associated with high histological and/or nuclear grades. When the TNBCs are divided into two subtypes by the presence of basal markers, the clinicopathologic characteristics of TNBCs were mainly maintained in the BLBCs. The 5-subgrouping was the better prediction model for both disease free and overall survival in breast cancers than the 4-subgrouping. After multivariate analysis of TNBCs, the BLBCs did not have a worse prognosis than the QNBC/5NPs. Interestingly, the patients with BLBCs showed significant adjuvant chemotherapy benefit. In addition, QNBC/5NPs comprised about 6~8% of breast cancers in publicly available breast cancer datasetsConclusionThe QNBC/5NP subtype is a worse prognostic subgroup of TNBCs, especially in higher stage and this result may be related to adjuvant chemotherapy benefit of BLBCs, calling for caution in the identification of subgroups of patients for therapeutic classification.

CpG island hypermethylation of E-cadherin (CDH1) and integrin α4 is associated with recurrence of early stage esophageal squamous cell carcinoma

The prognosis of esophageal squamous cell carcinoma (ESCC) patients remains very poor, which is partially due to a high rate of recurrence. This study was aimed at identifying a recurrence‐associated epigenetic prognostic marker in patients with ESCC. We retrospectively analyzed the CpG island hypermethylation of the p16, Wif‐1, sFRP1, integrin α4, CDH1, DAP kinase and RARβ2 genes in 251 ESCCs. The methylation status was determined by methylation‐specific PCR. Hypermethylation was detected in 52% for p16, 25% for RARβ2, 43% for CDH1, 21% for integrin α4, 57% for sFRP1, 38% for DAP kinase and 35% for Wif‐1. Recurrence was observed in 131 (52%) of the 251 cases. For stage I cancers, CDH1 methylation was associated with a high risk of recurrence (OR = 5.26, 95% CI = 1.48–18.67; p = 0.01) and a poor recurrence‐free survival after surgery (HR = 3.13, 95% CI = 1.21–8.09; p = 0.02). The hazard of failure after recurrence was about 13.17 (95% CI = 2.46–70.41; p = 0.003) times higher in patients with Wif‐1 methylation than in those without. For stage II cancers, integrin α4 methylation was associated with an increased risk of recurrence (OR = 3.03, 95% CI = 1.09–8.37; p = 0.03) and a poor recurrence‐free survival (HR = 2.12, 95% CI = 1.13–3.98; p = 0.03). In conclusion, the present study suggests that hypermethylation of CDH1 and integrin α4 genes may be used as recurrence‐associated prognostic indicators in stage I and stage II ESCCs, respectively.

Differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma and invasive ductal carcinoma of the breast: Matched case–control study

PURPOSE We designed this study to identify differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma (IDC) in patients with breast cancer. EXPERIMENTAL DESIGN We identified 72 cases of IMPC who were diagnosed between 1999 and 2007 at the Samsung Medical Center. These patients were matched with 144 controls who were diagnosed with IDC during the same period. Exact matches were made for age (+/-3 years), pathologic tumour and node stage, and treatment methods (surgery and radiation therapy). RESULTS The median follow-up period was 45 months (13-116) for IMPC and 50 months (16-122) for IDC. Lymphovascular invasion (LVI, p<0.0001), axillary lymph node extracapsular extension (ECE, p=0.001) and high nuclear grade (p=0.032) were more frequently detected in patients with IMPC. During the follow-up period, treatment failed in 15 IMPC patients (20.8%) and in 26 IDC patients (18.1%). Loco-regional recurrences developed in 11 IMPC patients (15.3%) and eight IDC patients (5.6%). Importantly, of 57 IMPC patients who had positive axillary nodes, seven patients (12.3%) had axilla and/or supraclavicular recurrence. Therefore, at 5 years, the loco-regional recurrence-free survival was 79.1% in the IMPC patients vs. 93.3% in the IDC patients (p=0.0024). CONCLUSION Our study showed that IMPC is associated with LVI, ECE, high nuclear grade, and a greater degree of loco-regional recurrence, especially in the axilla and supraclavicular areas. Therefore, axillary and supraclavicular radiation therapy should be considered in IMPC patients with axillary node metastasis.

Expression and amplification of Her2, EGFR and cyclin D1 in breast cancer: immunohistochemistry and chromogenic in situ hybridization.

Determination of Her2, epidermal growth factor receptor (EGFR) and cyclin D1 status is now of major clinical importance due to the development of molecule‐targeting drugs in anticancer therapy. Immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) are the most simple and convenient methods for evaluating gene alterations and their protein consequences. The purpose of the present study was to investigate the status of Her2, EGFR and cyclin D1 on both IHC and CISH in 95 primary breast carcinomas. There was substantial consistency between the IHC and CISH results of Her2 and EGFR, showing fair agreement between protein overexpression and gene amplification. However, cyclin D amplification was not related to protein overexpression. Moreover, there was no correlation between Her2, EGFR and cyclin D1. Her2 protein overexpression and amplification were positively associated with histological grade, nuclear grade and inversely correlated with the expression of estrogen receptor (ER) and progesterone receptor (PR). In ER‐negative and postmenopausal patients, EGFR gene amplification was strongly associated with worse recurrence‐free survival (P = 0.0087, P = 0.0149, respectively). Overall, the present findings suggest that EGFR gene amplification is important in predicting prognosis and this should be evaluated in breast carcinoma in addition to Her2 status in routine pathological practice.

Comparison of Her-2, EGFR and cyclin D1 in primary breast cancer and paired metastatic lymph nodes: an immunohistochemical and chromogenic in situ hybridization study.

The significant advance in the development of molecular-targeting drugs has made an evaluation of Her-2, EGFR, and cyclin D1 an important clinical issue in breast cancer patients. This study compared the Her-2, EGFR, and cyclin D1 status of primary tumors as well as their matching lymph node metastases using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in 73 breast cancer patients. Her-2, EGFR, and cyclin D1 protein showed a concordance between the primary lesion and the metastatic regional lymph nodes in 82%, 90%, and 63%, respectively. CISH also revealed 92%, 93%, and 85% concordance in the gene amplification status of Her-2, EGFR, and cyclin D1, showing a reasonable agreement between primary tumors and metastatic regional lymph nodes. Although a statistically significant agreement was found in Her-2 expression, a relatively high discordance rate (18%) raises a little concern. Our findings suggest that the Her-2 status can be reliably assessed on primary tumor but a possible difference can be found in Her-2, EGFR, and cyclin D1 status between the primary and the metastatic sites and this possibility should be concerned in patients considering molecular targeted therapy or patients with progress of disease.

Immunoexpression of inhibin alpha-subunit in adrenal neoplasms.

Inhibin normally is produced by ovarian granulosa cells and testicular Sertoli cells. Extragonadal inhibin expression also has been detected in the placenta, pituitary gland, and liver. It may be difficult to make a distinction between adrenal cortical tumors, pheochromocytoma, and metastatic carcinomas including renal cell and hepatocellular carcinoma. Immunohistochemical expression of inhibin alpha-subunit was evaluated to determine whether any usefulness of immunostaining could be found for inhibin alpha-subunit in the differential diagnosis of adrenal glandular lesions. The authors performed immunostaining against inhibin alpha-subunit on 5 cases of normal adrenal gland, 1 case of adrenal cortical hyperplasia, 25 cases of adrenal cortical adenoma, 6 cases of adrenal cortical carcinoma, 21 cases of pheochromocytoma, 8 cases of metastatic carcinoma, and 10 cases of primary renal cell carcinoma. Normal adrenal gland showed a strong immunoreactivity against inhibin alpha-subunit, especially in the inner layer of the adrenal cortex, representing the zona reticularis, but adrenal medulla was negative for inhibin alpha-subunit. Adrenal cortical hyperplasia associated with Cushings syndrome showed a strong, diffuse immunoreactivity for inhibin alpha-subunit. Immunoreactivity against the inhibin alpha-subunit was identified in all cases of adrenal cortical adenoma and carcinoma, especially in the adrenal cortical neoplasm with Cushings syndrome, which showed a strong reactivity. However, immunoreactivity was absent in two metastatic carcinomas from the liver and colon and most of the pheochromocytomas, except three cases with weak focal positivity for inhibin alpha-subunit. Four cases of metastatic renal cell carcinoma and 10 cases of primary renal cell carcinoma revealed no immunoreactivity. Metastatic adenocarcinoma from the prostate showed a weak immunoreactivity for inhibin alpha-subunit. Metastatic hepatoblastoma was negative against inhibin alpha-subunit with endogenous biotin blocking. Immunoexpression for inhibin alpha-subunit is useful for making distinction between adrenal cortical tumors, pheochromocytoma, and metastatic carcinoma. Inhibin alpha-subunit may be valuable as part of a diagnostic immunohistochemical panel in adrenal glandular lesions.

Sonography of Axillary Masses What Should Be Considered Other Than the Lymph Nodes

Objective. The purpose of this study was to review the sonographic findings of various axillary masses other than lymph nodes in correlation with other imaging and pathologic findings. Methods. From a sonographic database, we collected interesting cases of axillary masses with pathologic or other imaging corroboration from the last 10 years. Results. Images of various soft tissue masses were reviewed. They included masses associated with accessory breasts (fibroadenomas, hamartomas, fat necrosis, and cancer arising from axillary breasts), other soft tissue masses (lipomas, schwannomas, hemangiomas, fibromatosis, epidermoid cysts, and malignant fibrous histiocytomas), and complications presenting as masses after axillary lymph node dissection (seromas, hematomas, suture granulomas, pseudoaneurysms, and lymphangiectasia). Conclusions. Awareness of the characteristic sonographic findings of various disease entities that cause axillary masses will help in the correct diagnosis of axillary masses.