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We aimed to investigate the prognostic influence of primary tumor site on the survival of patients with breast cancer.Data of 63,388 patients with primary breast cancer from the Korean Breast Cancer Registry were analyzed. Primary tumor sites were classified into 5 groups: upper outer quadrant, lower outer quadrant, upper inner quadrant, lower inner quadrant (LIQ), and central portion. We analyzed overall survival (OS) and breast cancer-specific survival (BCSS) according to primary tumor site.Central portion and LIQ showed lower survival rates regarding both OS and BCSS compared with the other 3 quadrants (all P .05) and hazard ratios were 1.267 (95% CI, 1.180-1.360, P .001) and 1.215 (95% CI, 1.097-1.345, P .001), respectively. Although central portion showed more unfavorable clinicopathologic features, LIQ showed more favorable features than the other 3 quadrants. Primary tumor site was a significant factor in univariate and multivariate analyses for OS and BCSS (all P .001). For lymph node-negative patients, LIQ showed a worse OS than the other primary tumor sites in the subgroup with no chemotherapy (P .001), but that effect disappeared in the subgroup with chemotherapy (P = .058).LIQ showed a worse prognosis despite having more favorable clinicopathologic features than other tumor locations and it was more prominent for lymph node-negative patients who received no chemotherapy. The hypothesis of possible hidden internal mammary node metastasis could be suggested to play a key role in LIQ lesions.

Purpose: Breast cancers in the early phase frequently undergo distant metastasis and survival of patients is greatly dependent on distant metastasis. The occurrence of micrometastasis has been suggested to relate with prognostic features of breast cancer, such as lymph node metastasis and the presence of vascular invasion. The aim of this study was to examine the presence of keratin-19 mRNA of epithelial tumors in bone marrow aspirates obtained from breast cancer patients and its possible correlation with tumor staging and disease-free survival. Methods: Bone marrow samples were obtained from 59 breast cancer patients at the time of surgery. We separated the mononuclear fraction from the samples and carried out nested reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of keratin-19 mRNA with two different pairs of primers. After operation, the patients were followed up at 3month intervals. We studied the possible correlation of the detection of keratin-19 mRNA with tumor size, nodal involvement, stage and recurrence rate. Results: Bone marrow micrometastasis was detected by nested RT-PCR for keratin-19 mRNA in one of four patients with ductal carcinoma in situ (DCIS), 13 of 30 patients with T1, 11 of 20 patients with T2 and all four patients with T3 lesion. Recurrence was observed in seven cases and all of them were positive for micrometastasis in bone marrow. Conclusion: The method of nested RT-PCR to detect the presence of keratin-19 mRNA in bone marrow from patients with breast cancer is sensitive and reliable. Moreover, early recurrence was observed in the patients with the tumor mRNA detected in bone marrow. Additional studies with larger numbers of patients and longer follow-up are desirable.

To document the imaging characteristics of subcutaneous and musculoskeletal sparganosis.Ten patients with musculoskeletal sparganosis were examined, with a variety of imaging modalities including MRI (n=6), ultrasonography (n=8), plain radiography (n=7) and CT (n=1). Pathologic correlation was carried out in all cases.Nine lesions involved soft tissues, of which seven were in the thigh, two in the trunk and one involved a vertebral body. The majority of the lesions in soft tissue were confined to the subcutaneous layer but two extended deep into underlying muscles. Sonography revealed low-echoic serpiginous tubular tracts (8/8), and an intraluminal echogenic structure (4/8). MRI revealed multiple serpiginous tubular tracts and peripheral rim enhancement. Two patients showed perilesional soft tissue edema. Pathologically, the lesion consisted of a larva surrounded by three layers of inflammation: an inner epithelioid granulomatous cell layer, middle chronic inflammatory cell layers, and an outer fibrous layer.The study suggests that if serpiginous tubular tracts are seen at imaging studies, musculoskeletal sparganosis should be included in the differential diagnosis.

Structural and functional changes in the major apurinic/apyrimidinic DNA endonuclease (APEX) gene in human colorectal cancers were investigated. DNAs were prepared from surgically removed 25 human colorectal tissues and direct sequencing of PCR-amplified APEX gene covering the entire protein coding region was performed. Point mutations in 3 and silent mutations in 3 out of 25 colorectal cancer patients were found. Base substitutions in intron Ⅱ were also found in 2 patients. T ↔ C or some A ↔ G transitions were the most typical pattern of the mutations. AP DNA endonuclease (APE) activities in normal and tumor tissues were 65.7 EU/㎎ and 21.7 EU/㎎, respectively. APEX protein was detected in both normal and tumor tissues and no remarkable difference in the amount of APEX protein between colorectal cancer tissues and their normal counterparts was observed. The incidence of APEX gene mutation in colorectal cancer was 12% which is relatively lower than that of other genes associated with colorectal tumor, but a significant reduction of APE enzyme activities in tumor tissues, especially in those with APEX mutations, was observed. These results indicate that the decreased APE enzyme activity might be closely related to the colorectal tumorigenesis, although no quantitative correlation between APE enzyme activity and APEX content exists.

Focal adhesion kinase (FAK) is an intracellular kinase that localizes to focal adhesions. FAK is overexpressed in human tumours, and FAK regulates both cellular adhesion and anti-apoptotic survival signalling. Disruption of FAK function by overexpression of the FAK C-terminal domain [FAK-CD, analogous to the FRNK (FAK-related non-kinase) protein] leads to loss of adhesion and apoptosis in tumour cells. We have shown that overexpression of an activated form of the Src tyrosine kinase suppressed the loss of adhesion induced by dominant-negative; adenoviral FAK-CD and decreased the apoptotic response in BT474 and MCF-7 breast cancer cell lines. This adhesion-dependent apoptosis was increased by the Src-family kinase inhibitor PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine}. We have also shown that expression of activated Src in breast cancer cells increased the expression of α2-integrin and that overexpression of α2-integrin suppressed FAK-CD-mediated loss of adhesion. Our results suggest a model in which Src regulates adhesion and survival through enhanced expression of the α2-integrin. This provides a mechanism through which Src promotes cellular adhesion and alters the adhesive function of FAK.

Human chondrosarcoma is a malignancy that has no effective systemic therapy, making the interruption of the metastatic cascade critical to enhance patient survival. The processes of local invasion and metastases share similar mechanisms at a cellular level. Focal adhesion kinase (FAK) has been implicated in local invasion of malignant tumor cells. In the current manuscript we examine the effect of FAK inhibition on cell attachment to extracellular matrix (ECM) and in vitro invasion. Bovine articular chondrocytes and two human chondrosarcoma cell lines were utilized to examine FAK activity in tumor cell invasiveness. Endogenous FAK activity was inhibited by adenoviral transfection with the C-terminal domain of FAK. This inhibition resulted from decreased FAK phosphorylation, while FAK expression remained unchanged. Inhibition of FAK phosphorylation and hence its activity lead to decreased cell adhesion to Type II collagen and decreased cell invasiveness. These effects were not due to changes in integrin expression, indicating that the inhibition was the result of disruption of outside: in signaling. There are three important aspects to these results. The first is that interruption of transmembrane signaling can affect cell attachment. The second is that in chondrosarcoma, cell differentiation correlates with FAK expression and metastatic potential. Thirdly, that cell invasiveness correlates with FAK activity and implies a mechanistic role for this molecular complex in local invasion and metastasis.

Purpose: To evaluate the usefulness of ultrasound-guided mammotome biopsy for microcalcification and to suggest a new approach for the localization of microcalcifications which are not detected on ultrasound. Materials and Methods: Twenty-one calcific lesions in 21 women (aged 33-56 years) underwent ultrasoundguided, vacuum-assisted, mammotome biopsy and a mean of 14 specimens per lesion were obtained. Calcification retrieval was defined as identification of calcifications on specimen radiographs. In the 13 cases of calcifications which were not detected on ultrasound imaging, mammotome biopsy was performed after localization of one or two needles at the microcalcifications under mammography-guidance. Radiographs of the specimens and histologic findings were reviewed and scheduled follow-up imaging was performed for evaluation of the complications of biopsy. Results: Ultrasound-guided, vacuum-assisted, mammotome biopsy removed all calcifications in 21 lesions. Eight (38%) lesions showed visible calcification on the ultrasound while 13 (62%) lesions were invisible, which underwent mammotome biopsy after needle localization under mammography-guidance. Surgery revealed DCIS in 1 (4.8%) of 21 lesions, infiltrating ductal carcinoma in two (9.5%), fibroadenomas with calcifications in 6 (28.6%), fibroadenomas with adenosis in 2 (9.5%), and fibrocystic change with calcifications in 10 (47.6%). Clinical significant complications did not occur on follow-up examination in any of the cases. Conclusion: Ultrasound-guided, vacuum-assisted, mammotome biopsy was an effective method for microcalcifications on mammogram. The results suggested that mammotome biopsy after mammogram-guided, needle localization is a good alternative method for the diagnosis of microcalcifications which are undetectable in the ultrasound images.

Purpose: Early detection and treatment of cancer is a primary focus of health care. Many serum markers are available for breast cancer, but are not good enough for screening. Cancer antigen CA 15-3 is the most widely used biomarker for breast cancer. However, CA 15-3 has low sensitivity and specificity. This study was performed to analyze the serum proteomic pattern in breast cancer patients by surface-enhanced laser desoption/ionization timeof-flight (SELDI-TOF). Methods: We screened for potential tumor biomarkers in 42 serum samples, including samples from a group of 23 breast cancer patients at different clinical stages [stage I (n=3), stage II (n=11), stage III (n=6), and stage IV (n=1)], and a control group of 19 healthy women. Diluted serum samples were applied to a C16 hydrophobic interaction chip (H4). Complex protein profiles of different groups were compared and analyzed using the Protein Chip software 2.1 (Ciphergen Biosystems). Results: There were 7 significant protein peaks in the breast cancer group and 5 in the control group. Scoring the expression of each peak, the mean score was 8.5 in the cancer group and 3.5 in the control. The results of the combination of each peak were highly sensitive (91.2%) and specific (94.7%). These proteomic patterns did not correlate with tumor stage and hormonal receptor, c-erb B2. Conclusion: In this preliminary report, we identified protein profiles that were differentiated in breast cancer patients. After proper validation, serum proteomic pattern analysis may ultimately be applied in screening breast cancer as a stand-alone or combined with current options. (Journal of Korean Breast Cancer Society 2004;7:22-26) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Purpose : We propose that cell attachment and invasion can be regulated by the modulation of FAK expression in chondrosarcoma cell lines. Materials and Methods : The C-terminal domain of FAK (FAK-CD) was transfected by recombinant adenovirus infection in chondrosarcoma cell lines, JJ012 and 105KC. The expression of FAK, FAK-CD and tyrosine phosphorylation were checked. Chondrocytes and chondrosarcoma cells were used in cell attachment tests by blocking or not blocking integrin-1 antibodies and synthetic peptides on type II collagen. To evaluate the effect of cell invasiveness, a wound healing assay and a Boyden chamber assay were done after FAKCD transfection. Results : We observed higher FAK expression in the chondrosarcoma cells than in chondrocytes. The level of attachment to type II collagen was significantly inhibited by blocking with the antibody of integrin-1 and synthetic RGD peptides. Also, the adenovirus mediated transfection of FAK-CD resulted in the inhibition of the phosphorylation of FAK and significant inhibition of cell attachment in only JJ012, without changing FAK expression. Moreover, migration after transfection with FAK-CD was reduced by up to 79.9% for JJ012 and 75.5% for 105KC. Conclusion : Attachment of chondrosarcoma cells could be mediated through integrin-1. We conclude that modified AK expression contributes to the suppression of tumor cell attachment and invasion.

Purpose: Sentinel lymph node (SLN) biopsy is a useful method for assessing axillary nodal status and selecting axillary dissection in breast cancer patients. The goals of our study were to evaluate the detection rate of SLN and determine the accuracy of SLN biopsy in predicting axillary nodal status using technetium radiolabeled sulfur colloid and isosulfan blue dye. Method.: Between January and August 2001, 55 breast cancer patients with clinically node negative results underwent SLN biopsy from the Department of Surgery at Ajou University Hospital. Both technetium radiolabeled sulfur colloid and isosulfan blue dye were used to guide SLN biopsy. SLN biopsy was always followed by a complete axillary dissection. The histopathology of SLNs determined from frozen sectioning and serial sectioning was compared with that of the nonsentinel nodes evaluated with routine Hematoxylin and Eosin stain. ResuIts: The overall SLN detection rate was 85.4% (47 of 55 patients). The staging accuracy of SLN biopsy was 97.9% (46 of 47 patients), the sensitivity 92.3% (12/13), the false negative rate 7.7% (1/13), and the negative predictive value 97.1% (34 of 35). Conclusion: Our study was a pilot study for SLN biopsy. SLN biopsy was more effective when a combination of technetium radiolabeled sulfur colloid and isosulfan blue dye were used. The results of our study support the hypothesis that SLN biopsy is an accurate predictor of axillary nodal status. SLN biopsy may be applicable to early breast cancer patients and thereby allow the omission of routine axillary dissection in selected cases.

Metastasis of breast carcinoma to the stomach is relatively uncommon, although metastasis to other organs such as lung, bone, and lymph nodes is not rare. It may cause difficulty in differentiating from primary gastric carcinoma. We report a case of signet ring cell carcinoma of the breast with metastasis to the stomach with illustrations of histologic findings of both lesions. The results of immunohistochemical stainining with GCDFP-15 (gross cystic disease fluid protein-15), that can be used to differentiate primary gastric signet ring cell carcinoma and metastatic mammary signet ring cell carcinoma, are described.