Expression of Interferon Regulatory Factors in Breast Cancer Tissue / 한국유방암학회지

PURPOSE: As neoplasia is the result of unbalanced cell growth and cell death, alternations in the growth control pathway including the immunity within the individual host-tumor relationship has been attributed to the development of breast cancer. Interferon(IFN)-gamma based immunity was recently reported to have an antitumor effect and some new methods to assess the state of interferon-gamma based immunity have been introduced. Interferon regulatory factor(IRF)-1 and interferon regulatory factor(IRF)-2 are transcriptional factors that mediate the effects of Interferon-gamma. It was suggested that the loss of IRF-1 expression is associated with the loss of tumor suppression and the development of IRF-2 expression is associated with oncogenic activation. Thus, we studied the significances of the IRF-1 and IRF-2 expressions as they are related with some clinicopathological parameters to determine the biological behavior of breast cancer including the menopausal status, tumor size, lymph node status, histologic grade, the expression of steroid receptors, the expression of c-erb B2 oncoprotein and the expression of p53 protein. METHODS: Formalin-fixed paraffin embedded specimens from 82 patients with invasive ductal carcinoma were used to evaluate the expression of IRF-1 and IRF-2 by performing immunohistochemical staining with using an avidin-biotin-peroxidase complex technique. RESULTS: The expression of IRF-1 was observed in 80.5 % of the study group. However, the expression of IRF-1 did not show any correlation with menopausal status, tumor size, histologic grade, the expression of steroid receptors, the expression of c-erb B2 oncoprotein and the p53 expression. Only lymph node metastasis showed a decreasing tendency of IRF-1 expression, but this was without statistical significance (p=0.075). The expression of IRF-2 was observed in 58.5% of the study group and it did not show any significant relationship with any of the above mentioned clinicopathological parameters. CONCLUSION: This study suggests that the expression of IRF-1 and IRF-2 does not affect the previously established parameters for determining such biological behaviors of breast cancer as the tumor size, lymph node metastasis, the histologic grade, the expression of steroid receptors, the expression of c-erb B2 and the expression of p53. In spite of these results, We'd like to recommend that another study be done to evaluate the role of IRF-1 and IRF-2 for the proper selection of the patients who are suitable for immunotherapy.

In Vitro Induction of Carcinoembryonic Antigen (CEA) Specific Cytotoxic T Lymphocytes Using Dendritic Cells Pulsed with CEA Peptide

PURPOSE: Dendritic cells (DCs) are the most potent antigen- presenting cells for initiating the T cell immune response in vivo. Recent studies have shown that active immunotherapy with tumor antigen pulsed DC tumor antigen specific cytotoxic T lymphocyte (CTL) response. The aim of this study was to establish clinically compatible procedures for generating human DCs and to determine if the CEA peptide- pulsed DCs can activate the CEA specific CTL responses in vitro. METHODS: DCs were generated from the peripheral blood monocytes (PBMCs) of HLA A2+ healthy donors using GM-CSF and IL-4. Phenotypic analysis was performed using flow cytometry with FITC- or PE-conjugated Abs against CD1a, CD14, CD80, HLA-DR, CD83 and CD86. The immature DCs were pulsed with a CEA peptide (HLA A2 epitope, [YLSGANLNL]) and the tumor lysates isolated from HLA A2+ CEA positive cell line, NCI-H498, and were incubated with the autologous PBMCs in order to generate an antigen specific CTLs in vitro. After three rounds of stimulation, the presence of a CEA-specific CTL response was determined using a CEA positive cell line as the specific targets with the standard 51Cr release assay, the ELISPOT assay, and the flow cytometry using CEA peptide-MHC tetramer. RESULTS: The DCs obtained after 6 days of culture expressed high levels of CD1a, HLA-DR, and CD80, which corresponded to the immature DC phenotype. The 51Cr- release assay showed that DCs pulsed with the CEA peptide or the lysates of the CEA-positive NCI-H498 cell line could stimulate the CEA-specific CTL responses. The CTL response to DCs pulsed with the CEA peptide was also generated using the DCs pulsed with the CEA peptide. In the ELISPOT assay, the number of CEA peptide-specific, INF-gamma-secreting spots were increased in the CTLs generated by DCs pulsed with the CEA pepide and the tumor lysates. In the peptide-MHC tetramer assay, the CD8+ T cells with the receptors specific to CEA-peptide were increased by stimulation with the DCs pulsed with the CEA peptide and the tumor lysates. CONCLUSION: These findings show that the CEA peptide pulsed DCs can generate CEA specific CTL responses and antigen bearing DCs can be used as the target cells for a cytotoxicity assay. This study provides the foundations for DC-based cancer immunotherapy for CEA expressing solid tumors.

Clinical Significance of Solitary Costal Hot Spot on Postoperative Bone Scan in Patients with Breast Cancer / 한국유방암학회지

PURPOSE: Bone is the most common site of metastasis from breast cancer. An abnormal bone scan finding, however, is not specific in differentiation of bone metastasis from traumatic or inflammatory bone diseases. The purpose of this study was to identify clinical findings that could help evaluate the etiology of solitary costal hot spots on a bone scan. METHODS: The study included 32 patients (all women, mean age 51+/-1 years) showing solitary costal hot spots on postoperative bone scans performed between January 1998 and December 2002. In order to classify the etiology of solitary costal hot spots as non-malignant or malignant, all available clinical, scintigraphic, laboratory and other radiographic examinations were taken into consideration. RESULTS: The mean follow-up period was 42.5 months. Among 32 hot spots, 7 (21.8%) were metastatic, and the remaining 25 (78.2%) non-malignant. The mean period of first detection after operation was 17.0+/-16.3 months in the metastatic and 26.0+/-21.3 months in the non-malignant groups. The metastatic group was significantly associated with advanced breast cancer. In the localization of rib lesion, 20 (62.5%) of the solitary costal hot spots were in the anterior arc, 5 (15.6%) in the lateral arc and 7 (21.9%) in the posterior arc. In the group with a location at the anterior arc, 16 (80%) were non-malignant, whereas 4 (20%) were malignant. In those localized at the anterior arc, 12 (60%) were on ipsilateral and 8 (28%) were on contralateral. The difference between the hot spots in the ipsilateral and contralateral locations was not significant. The carcinoembryonic antigen (CEA) and CA15-3 were elevated: in 5 (51%) and 3 (43%) patients with metastatic spots, and in 4 (16%) and 1 (4%) patient with non-malignant lesions, which were significantly different. CONCLUSION: It was found that an advanced state of primary breast cancer and the increase of tumor markers (CEA and CA15-3) were the significant factors for the direction of the nature of solitary costal hot spots on postoperative bone scans in patients with breast cancer.

Three Cases of Elderly Women with Breast Cancer treated with Non-operative Methods / 한국유방암학회지

The mainstay of treatment in primary breast cancer is still a radical mastectomy. In the case of advanced breast cancer, preoperative chemotherapy is an alternative treatment method to induce surgical therapy. Although the number of elderly patients with breast cancer is increasing, the knowledge about the possible differences in the biology and clinical outcomes of breast cancer according to age is limited. In addition, elderly patients have difficulties with surgical treatment because of the higher rate of coincident systemic illness, high anesthetic risk and high rate of operation refusals for an operation than those in young patients. As it was well known that elderly patients have better prognoses than younger patients and more estrogen and progesterone receptors in tumor tissue, it was expected that oral chemoendocrine and radiation therapy could be an alternative in elderly patients who refuse surgery. Good results were experienced in our three elderly breast cancer patients when applying these non-surgical treatments.

Clinical Analysis of T4 Colorectal Cancer with Adhesion to Adjacent Organs

PURPOSE: A colorectal cancer (CRC) is defined as T4 when the tumor directly invades other organs or structures and/or perforates the visceral peritoneum. The purpose of this study was to evaluate the results of a surgical approach and to determine the significant prognostic factors for tumor resectability and survival in patients with advanced T4 CRC. METHODS: A total of 61 patients with T4 CRC with adjacent organ adhesion, who received multivisceral resections at Chonnam University Hospital, Korea, between Jan. 1990 and Dec. 2001, were analyzed retrospectively. RESULTS: Cancer invasion to contiguous organs was present in 51 (83.6%) of the 61 patients who received a multivisceral resection and was absent in 10 (16.4%). Postoperative rates of complications and death were 22.9% and 4.9%, respectively, in the 61 patients. Lymph-node (LN) metastases were presented in 25 patients (41.0%). The 5-year survival rate (5 YSR) was 22.2% in patients with LN metastases, but was significantly higher (66.7%) in patients without LN metastases. The 5 YSRs for the 61 patients according to the AJCC cancer stage (TNM classification) were as follows: stage II (66.7%), stage III (46.4%), and stage IV (0%). CONCLUSIONS: T4 CRC without distant metastases requires multivisceral en-bloc resection of any organ or structure to which the primary tumor is adhered. The presence of LN metastases at the time of surgery is one of the significant factors with a poor prognosis in T4 CRC.