Eunah Shin

HER2 status in pure ductal carcinoma in situ and in the intraductal and invasive components of invasive ductal carcinoma determined by fluorescence in situ hybridization and immunohistochemistry

Aim : To determine the HER2 status of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. The increased prevalence of HER2 amplification and overexpression in DCIS is considered to be maintained in the intraductal component of IDC; however, HER2 amplification and overexpression are detected much less in IDC.

The prognostic significance of growth factors and growth factor receptors in gastric adenocarcinoma

We evaluated growth factors/receptors expression in gastric adenocarcinoma. Immunohistochemistry was used to evaluate epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), VEGF‐D, VEGF receptor (VEGFR)‐2, VEGFR‐3, transforming growth factor (TGF)‐α, TGF‐β1, and TGF‐β‐RII in tissue microarrays of adenocarcinoma, dysplasia, metaplasia, and gastritis. In adenocarcinoma, the expression rates of EGFR, VEGF, VEGF‐D, VEGFR‐2, VEGFR‐3, TGF‐α, TGF‐β1, and TGF‐β‐RII were 2.0%, 0%, 10.7%, 4.4%, 11.2%, 26.3%, 9.4%, and 19.5%, respectively. VEGF‐D, TGF‐α, TGF‐β1, and TGF‐β‐RII expression rate were higher in adenocarcinoma than in other groups. TGF‐β‐RII expression was correlated with VEGFR‐3, VEGF‐D, and TGF‐α expression in adenocarcinomas. Tumor location, histologic type, stage, lymphatic invasion, perineural invasion, angioinvasion, VEGF‐D, and VEGFR‐2 expressions were associated with patient survival in a log rank test and advanced stage and positive expression of VEGF‐D were poor prognostic factors using Cox analysis. VEGF‐D expression may be of prognostic value in gastric adenocarcinoma, whereas EGFR and TGF family expression may only have a minor influence.

Osteopontin, CD44, and NFκB Expression in Gastric Adenocarcinoma

PURPOSE Osteopontin (OPN) binds to CD44 and nuclear factor-kappaB (NFkappaB) and OPN mediates tumorigenesis, invasion and metastasis, but the interrelationships between OPN, CD44 and NFkappaB are not fully understood, and especially in gastric carcinogenesis. We examined the expressions of OPN, CD44, and NFkappaB in untreated gastric adenocarcinomas. MATERIALS AND METHODS The materials from 211 cases of gastric adenocarcinoma were immunostained for OPN, CD44 and NFkappaB by using a tissue microarray. The OPN mRNA expression was measured in 10 cases by performing real-time RT-PCR. RESULTS The expression of OPN, CD44 and NFkappaB was noted in 61.7%, 11.4% and 26.6% of the adenocarcinoma tissues, respectively. No significant correlation was detected among the expressions of these proteins. The OPN protein expression was negatively correlated with angioinvasion (p<0.05) and patient survival (p<0.05), whereas the CD44 and NFkappaB protein expressions were not correlated with any of the clinicopathological factors we examined. The depth of invasion, lymph node status and perineural invasions were prognostic factors based on the Cox analysis. The OPN mRNA expression showed no significant difference between the adenocarcinoma and the paired normal mucosa on real-time RT-PCR. CONCLUSION OPN may have a currently undetermined role in gastric carcinogenesis, and CD44 and NFkappaB may have minor roles in gastric adenocarcinoma.

Osteopontin, CD44, and NFkappaB expression in gastric adenocarcinoma.

PURPOSE Osteopontin (OPN) binds to CD44 and nuclear factor-kappaB (NFkappaB) and OPN mediates tumorigenesis, invasion and metastasis, but the interrelationships between OPN, CD44 and NFkappaB are not fully understood, and especially in gastric carcinogenesis. We examined the expressions of OPN, CD44, and NFkappaB in untreated gastric adenocarcinomas. MATERIALS AND METHODS The materials from 211 cases of gastric adenocarcinoma were immunostained for OPN, CD44 and NFkappaB by using a tissue microarray. The OPN mRNA expression was measured in 10 cases by performing real-time RT-PCR. RESULTS The expression of OPN, CD44 and NFkappaB was noted in 61.7%, 11.4% and 26.6% of the adenocarcinoma tissues, respectively. No significant correlation was detected among the expressions of these proteins. The OPN protein expression was negatively correlated with angioinvasion (p<0.05) and patient survival (p<0.05), whereas the CD44 and NFkappaB protein expressions were not correlated with any of the clinicopathological factors we examined. The depth of invasion, lymph node status and perineural invasions were prognostic factors based on the Cox analysis. The OPN mRNA expression showed no significant difference between the adenocarcinoma and the paired normal mucosa on real-time RT-PCR. CONCLUSION OPN may have a currently undetermined role in gastric carcinogenesis, and CD44 and NFkappaB may have minor roles in gastric adenocarcinoma.

Clinical significance of p27 and Skp2 protein expression in uterine cervical neoplasm.

Summary: The loss of p27 indicates a poor prognosis in various solid tumors, and a decrease in p27 level is the result of increased degradation by Skp2. We evaluated the relationship of p27 and Skp2 protein expression to various clinicopathologic factors in 332 cases of untreated uterine cervical neoplasm using tissue microarray method. After immunohistochemical staining, 313 and 300 tumor samples were retrieved for interpretation for p27 and Skp2, respectively. High p27 protein expression (nuclear staining in more than 30% of the tumor cells) was seen in 39.9% (125/313 cases), including 32 cervical intraepithelial neoplasia (CIN) III (55.2%), 58 microinvasive squamous cell carcinoma (SCC) (56.9%), 21 invasive SCC (17.1%), 11 adenocarcinoma (55.0%), and 3 cases of other tumors (30.0%). High Skp2 protein expression was noted in 28.3% (85/300 cases), including 14 cervical intraepithelial neoplasia III (25.0%), 18 microinvasive SCC (18.75%), 45 invasive SCC (37.8%), 6 adenocarcinoma (30.0%), and 2 cases of other tumors (22.2%). Low p27 protein expression was correlated with large tumor size (P < 0.005), depth of invasion in squamous lesion (P < 0.0005), high stage (P < 0.0005), and poor survival (P < 0.005). High Skp2 protein expression was correlated with large tumor size (P < 0.05), depth of invasion in squamous lesion (P < 0.05), and high stage (P < 0.005), but not with patient survival. There was no significant correlation between p27 and Skp2 protein expression. Only tumor stage had prognostic significance in the multivariate analysis (P = 0.041). Patients with low p27 protein expression had worse prognosis, indicating that p27 may participate in the progression of cervical squamous cell lesions.

Recurrence Rates and Characteristics of Phyllodes Tumors Diagnosed by Ultrasound-guided Vacuum-assisted Breast Biopsy (VABB)

Background/Aim: Recently, the development of ultrasonography (US)-guided vacuum-assisted breast biopsy (VABB) has enabled the excision of benign breast tumors with normal surrounding breast tissues; thus, complete excision is possible without residual tumor tissue. We sought to identify the clinicopathological characteristics and recurrence rates of benign phyllodes tumors diagnosed by US-guided VABB. Patients and Methods: Data from 11,221 US-guided VABBs performed at the Gangnam Cha Medical Center over 12 years were analyzed. Eighty-three lesions were diagnosed as benign phyllodes tumors; 67 with >24 months of follow-up data were investigated. All lesions were excised using an 8-gauge probe without residual tissue; patients underwent follow-up US every 3-6 months. Results: Five patients (7.46%) experienced local recurrence during a mean follow-up period of 27.8 months; no distant metastases occurred. The mean tumor size was 3.0 cm in the recurrence group and 1.87 cm in the non-recurrence group (p=0.05). Conclusion: Benign phyllodes tumors excised and diagnosed using VABB showed a low recurrence rate during the follow-up period; thus, these tumors, particularly those <3 cm, can be safely monitored with ultrasonography instead of performing immediate re-excision.

Expression of Epstein-Barr virus and granzyme B in cytologic smears of histiocytic necrotizing lymphadenitis.

Histiocytic necrotizing lymphadenitis (HNL) is a non‐neoplastic disease of the lymph nodes that is self‐limiting in its clinical course. In this study, the expression of Epstein‐Barr virus (EBV), granzyme B, and other phenotypic markers of HNL was investigated in fine needle‐aspirated (FNA) cytologic smears obtained from 38 patients with HNL. The smear were subjected to immunohistochemical staining for granzyme B, CD3, CD4, CD8, CD20, and CD68 in addition to in‐situ hybridization for EBV to determine whether marker expression could be correlated with disease pathogenesis. The mean age of 28 female and 10 male patients was 22.8 years. CD8‐positive cytotoxic T cells were noted in 65.0% of the smears (13/20 cases), whereas CD4 and CD68 were rarely observed. Granzyme B reactivity was seen in lymphocytes, especially in apoptotic areas, and in histiocytes, with positive rates of 25.0% (9/36) and 11.1% (4/36), respectively. Most FNA smears showed immunoreactivity to both CD3 and CD20, with a predominance of CD3‐positive cells. In‐situ hybridization for EBV was positive in 22.9% (8/35) of the cases. The immunohistochemical staining and EBV in‐situ hybridization results obtained in bleached FNA smears were similar to those in histologic sections. Overall, our results implicate that even though EBV positivity and granzyme B immunoreactivity are noted in HNL, they do not appear to have any apoptosis‐associated role. Diagn. Cytopathol. 2012.

Comparison of CVF (Cyclophosphamide+Vinorelbine+5-Fluorouracil) and CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil) Adjuvant Chemotherapy in Early Breast Cancer

Purpose Our study aimed to evaluate the feasibility of adjuvant cyclophosphamide/vinorelbine/5-fluorourail (CVF) chemotherapy as an alternative to cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy for treating early breast cancer. Methods One hundred and forty-nine patients were randomly assigned to CMF or CVF adjuvant chemotherapy for treating their early stage breast cancer between September 2000 and December 2007. The disease-free survival (DFS), the overall survival (OS), and the toxicity profiles of both groups were compared. Results Sixty-seven patients underwent CMF chemotherapy whereas 82 patients underwent CVF chemotherapy. The DFS and OS were 88 months (95% confidence interval [CI], 76-101 months) and 94 months (95% CI, 83-104 months), respectively for the CMF group, and 97 months (95% CI, 93-101 months), and 101 months (95% CI, 98-104 months), respectively for the CVF group. However, those survival gains of the CVF group were not statistically significant (p-value=0.069 for the DFS and 0.99 for the OS). The CVF group showed a favorable toxicity profile in terms of the grade 3/4 hematologic toxicities as compared to that of the CMF group. Conclusion Clinical outcome of CVF chemotherapy was comparable to CMF with a favorable toxicity profiles. However, it is difficult to conclude the feasibility of CVF regimen because of small number of studied patients.

Osteopontin, CD44, and NF

PURPOSE Osteopontin (OPN) binds to CD44 and nuclear factor-kappaB (NFkappaB) and OPN mediates tumorigenesis, invasion and metastasis, but the interrelationships between OPN, CD44 and NFkappaB are not fully understood, and especially in gastric carcinogenesis. We examined the expressions of OPN, CD44, and NFkappaB in untreated gastric adenocarcinomas. MATERIALS AND METHODS The materials from 211 cases of gastric adenocarcinoma were immunostained for OPN, CD44 and NFkappaB by using a tissue microarray. The OPN mRNA expression was measured in 10 cases by performing real-time RT-PCR. RESULTS The expression of OPN, CD44 and NFkappaB was noted in 61.7%, 11.4% and 26.6% of the adenocarcinoma tissues, respectively. No significant correlation was detected among the expressions of these proteins. The OPN protein expression was negatively correlated with angioinvasion (p<0.05) and patient survival (p<0.05), whereas the CD44 and NFkappaB protein expressions were not correlated with any of the clinicopathological factors we examined. The depth of invasion, lymph node status and perineural invasions were prognostic factors based on the Cox analysis. The OPN mRNA expression showed no significant difference between the adenocarcinoma and the paired normal mucosa on real-time RT-PCR. CONCLUSION OPN may have a currently undetermined role in gastric carcinogenesis, and CD44 and NFkappaB may have minor roles in gastric adenocarcinoma.