Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer

BACKGROUND: Triple negative breast cancer (TNBC) is defined as a lack of the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in breast cancer. Many TNBCs show a profound infiltration of tumor infiltrating lymphocytes (TILs). It is still uncertain whether these TILs are protumoral or antitumoral. Regulatory T cells (Tregs) play a role in inducing immune tolerance to antigens, and they may be selectively recruited by cancer cells. This study was conducted to evaluate the significance of TILs with an emphasis on forkhead box p3 (Foxp3), which is a marker for CD25+CD4+ Treg in TNBC. METHODS: We investigated the Foxp3, CD8 and CD4 expressions in 100 cases of TNBC by immunohistochemistry and using a tissue microarray. The Foxp3 expression was divided as the high and low infiltration groups (cut-off value=20). RESULTS: The high infiltration group was correlated with higher histologic and nuclear grades. However, Foxp3+ Tregs were decreased in the T3 and T4 TNBCs as compared to that of the T1 and T2 TNBCs. No significant differences were found for the nodal status, lymphovascular invasion, stage, recurrence and overall survival. CONCLUSIONS: High Foxp3+ Treg infiltration in TNBC is correlated with the nuclear and histologic grades, but there was no relation to recurrence and overall survival.

Frequency of Intrahepatic FoxP3+ Regulatory T cells during the Natural Course of Chronic Hepatitis B: An Immunohistochemical Study Using Needle-Biopsied Liver Tissue

BACKGROUND: Regulatory T cells (Tregs) may contribute to the immunological hyporesponsiveness against hepatitis B virus (HBV), and this can result in chronic infection. Tregs suppress the T cell responses directed against HBV and they protect hepatocytes by down-regulating the immune responses that cause liver damage, but the role of Tregs has not been well characterized. METHODS: Fifty four patients were selected and classified into three groups (12 were in the immune-tolerance phase, 35 were in the immune-clearance phase and 7 were in the asymptomatic virus carrier phase). We examined the frequency of CD3+, CD4+ & CD8+ T cells and forkhead box P3 (FoxP3)+ Tregs in the needle-biopsied liver tissue by performing immunohistochemistry. RESULTS: The FoxP3+ Tregs were mainly located at the portal tracts. In the immune-clearance phase, the frequency of FoxP3+ Tregs was significantly increased compared to that of the immune-tolerance group and the asymptomatic carrier group. Increased FoxP3+ T cells were observed in the patients with a higher histologic inflammatory index. No correlation was observed among the numbers of FoxP3+ Tregs, the serum alanine aminotransferase level, detection of HBeAg and the HBV-DNA viral load. CONCLUSIONS: FoxP3+ Tregs may play important roles in suppressing the immune response to HBV and the complete elimination of HBV.

Histopathological Evaluation of Pediatric Intestinal Pseudo-Obstruction: Quantitative Morphometric Analysis of Pathological Changes in the Enteric Nervous System

BACKGROUND: This study was done to obtain comprehensive data on changes in the structural components of the enteric nervous system in pediatric patients with intestinal pseudo-obstruction (IPO). We evaluated routinely processed, in formalin-fixed tissues by quantitative morphometric analysis. In addition, we used formalin-fixed tissue to explore the possibility of using previously proposed diagnostic criteria to evaluate frozen serial sections for intestinal neuronal dysplasia (IND) type B and hypoganglionosis. METHODS: We analyzed data for 19 IPO cases. Morphometric analysis for quantification of ganglia and ganglion cells (GCs) was done for the myentric and the submucous plexus. In addition, we determined the presence of immature GCs and the distribution of nerve fibers and interstitial cells of Cajal (ICC). RESULTS: Nine patients showed combined hypoganglionosis, IND, and decreased ICC; others showed various combinations of these. Several morphometric factors were significantly different between patient groups as well as being different than the control group. CONCLUSIONS: Our pediatric IPO cases showed extensive overlapping of pathological findings. And the findings suggest the utility of using previously proposed morphometrically measured factors in multiple frozen sections as diagnostic criteria for IND type B and hypoganglionosis in formalin-fixed tissue.

Microvessel and Lymphatic Vessel Density and VEGFR-3 Expression of Papillary Thyroid Carcinoma with Comparative Analysis of Clinicopathological Characteristics

BACKGROUND: This study was done to see if there were correlations between anatomic and molecular parameters such as microvessel density (MVD), lymphatic vessel density (LVD), and vascular endothelial growth factor receptor (VEGFR)-3 expression and various clinical parameters for papillary thyroid carcinomas of size > 1.0 cm (PTCs) and size 45 years old (more apparent in the PTC group) and LVD had suggestive correlations with multicentricity and extrathyroidal extension depending on analytic conditions. CONCLUSIONS: Since LVD showed variable correlations with clinical variables for papillary carcinoma of the thyroid depending on analytic conditions, the individually planned treatments based on overall clinicopathological factors are advised.

Cancer of Unknown Primary Finally Revealed to Be a Metastatic Prostate Cancer: A Case Report / Journal of the Korean Cancer Association, 대한암학회지

The vast majority of patients with metastatic prostate cancer present with bone metastases and high prostate specific antigen (PSA) level. Rarely, prostate cancer can develop in patients with normal PSA level. Here, we report a patient who presented with a periureteral tumor of unknown primary site that was confirmed as prostate adenocarcinoma after three years with using specific immunohistochemical examination. A 64-year old man was admitted to our hospital with left flank pain associated with masses on the left pelvic cavity with left hydronephrosis. All tumor markers including CEA, CA19-9, and PSA were within the normal range. After an exploratory mass excision and left nephrectomy, the pelvic mass was diagnosed as poorly differentiated carcinoma without specific positive immunohistochemical markers. At that time, we treated him as having a cancer of unknown primary site. After approximately three years later, he revisited the hospital with a complaint of right shoulder pain. A right scapular mass was newly detected with a high serum PSA level (101.7 ng/ml). Tissues from the scapular mass and prostate revealed prostate cancer with positive immunoreactivity for P504S, a new prostate cancer-specific gene. The histological findings were the same as the previous pelvic mass; however, positive staining for PSA was observed only in the prostate mass. This case demonstrates a patient with prostate cancer and negative serological test and tissue staining that turned out to be positive during progression. We suggest the usefulness of newly developed immunohistochemical markers such as P504S to determine the specific primary site of metastatic poorly differentiated adenocarcinoma in men.

Metaplastic Squamous Carcinoma of the Breast: Clinicopathologic Analysis of 17 Cases

BACKGROUND: Squamous cell carcinoma of the breast is very rare and it is considered to arise from metaplastic change of ductal carcinoma. Metaplastic squamous cell carcinoma (MSC) of the breast includes pure squamous cell carcinoma, metaplastic adenosquamous carcinoma and low grade adenosquamous carcinoma. Most of the cases of MSC of the breast were reported to have lymph node metastasis and this has a worse prognosis than that of conventional invasive ductal carcinoma. METHODS: We collected 17 cases of MSC of the breast from 1,173 cases of breast cancer and analyzed the clinicopathological characteristics. RESULTS: The age range was 31 to 69 years (mean age: 47.2). The mean tumor size was 3.6 cm. Twelve cases (70.6%) had a negative nodal status. The majority of the cases were of a high nuclear grade (grade III: 76.5%), and a high histologic grade (grade III: 88.2%). All the cases had no amplification of HER2, and they were negative for hormonal receptors, except for 2 cases with weak positivity. All the cases showed positivity for EGFR (3+: 14 cases, 1+: 3 cases). Clinical relapse was found in 3 patients on follow up and two of them expired due to lung and bone metastasis. CONCLUSIONS: MSC is associated with high nuclear and histologic grades, a high EGFR expression and they are triple negative for ER, PR, and HER2. The EGFR immunopositivity of MSC suggests a basal-like subtype.

A Case of Idiopathic Chronic Ulcerative Enteritis Presenting with Septic Shock / 대한소화기내시경학회지

Idiopathic chronic ulcerative enteritis (ICUE) is a rare disease with a mortality rate exceeding 75%, which manifests as an ulceration of the small bowel in the absence of a recognizable cause. It is diagnosed by biopsy. A 31-year-old man who had a 10-year history of recurrent episodes of abdominal pain was admitted with a 10-day occurrence of abdominal pain and fever. Upper endoscopy showed multiple active ulcers from duodenal second to distal portion. Colonoscopy revealed diffuse ulcerations at the terminal ileum. Colonic findings were normal. The patient was treated with intravenous antibiotics, systemic steroids, and total parenteral nutrition in the intensive care unit. Ten days after admission, the patient fell into shock due to massive hematochezia and underwent an emergency surgical resection, which revealed Meckel's diverticulum. Bleeding was uncontrolled and the following day surgical resection and intraoperative endoscopy of the highly involved jejunum revealed severe ulcerative bleeding. Microscopic examination revealed ulcerations with pseudopolyps and granulation tissue and no evidence of vasculitis, suggestive of ICUE.

Sudden rapid growth of an aggressive angiomyxoma after taking pomegranate seeds oil / 부인종양

Aggressive angiomyxoma (AA) is a rare soft tissue tumor of undetermined etiology that occurs mainly in the female vulva and perineum. It has been demonstrated to increase in size under the estrogenic stimulation and shown to respond to treatment with a GnRH agonist. A 47-year-old woman was presented with a large vulvar mass. The mass had grown slowly before she took pomegranate seeds oil on a regular basis for a year, which is known to contain natural estrogen for a year. The almond-sized mass enlarged into a fetal head-sized one in a year. Our case is implying that external administration of estrogenic substance may be a contributory factor to the sudden accelerated growth of AA. Although the past medical history in this case relies on an unverified observation by the patient alone, the unique clinical course and impressive gross appearance of AA may help clinicians with diagnosis in practice.

ISUP/WHO Classification of Papillary Urothelial Neoplasms of Urinary Bladder: Consensus Study Conducted by Korean Society of Urogenital Pathology

BACKGROUND: Pathologic grading, one of the most important prognostic factors of papillary urothelial neoplasia (PUN) of the urinary bladder, has been revised continuously. The current study focused on the analysis of interobserver agreement on PUN of the urinary bladder bet- ween 1973 WHO classification (WHO 1973) and 1998 WHO/ISUP classification. METHODS: Seventy five cases from 15 institutions were collected, and after review by Korean Society of Urogenital Pathology (KSUP), 30 cases were selected as follows; group I, WHO grade 1 and papillary urothelial neoplasm of low malignant potential by ISUP (7 cases), group II, WHO grade 2 and low-grade papillary urothelial carcinoma (16 cases), and group III, WHO grade 3 and high-grade papillary urothelial carcinoma (7 cases). Seventy five general surgical pathologists who participated in this study were asked to grade the tumors based on WHO/ISUP classification. Interobserver agreement between the participants' diagnosis and KSUP consensus diagnosis was analyzed by kappa value. RESULTS: Interobserver agreement assessed by kappa value for all diagnostic groups was very low; for group I, kappa value was -0.900893722; for group II, -0.944650025, and for group III, -0.876728996. The overall kappa value of pathology residents was better than that of practicing pathologists. CONCLUSIONS: The 1998 WHO/ ISUP classification could not be easily translated from the 1973 WHO classification and because of poor interobserver agreement, it appears that further work would be needed before it can be practically applied.

Study on consecutive light microscopic changes of tumor cells and apoptotic index observed in serial cervical biopsies during neoadjuvant chemotherapy with 5-fluorouracil and cisplatin in locally advanced cervical cancer / 부인종양

OBJECTIVE: To determine the effects of neoadjuvant chemotherapy (5-fluorouracil plus cisplatin) on tumor cell morphology and apoptosis by analyzing the consecutive changes of apoptotic index (AI) and histology observed in the serially obtained cervical cancer tissues during the chemotherapy. METHODS: Cervical cancer tissues were obtained by punch biopsy just before starting the each cycle of neoadjuvant chemotherapy from five patients with locally advanced disease (stage IIb-IIIb), but previously untreated squamous cell carcinoma of uterine cervix. All patients were treated with three cycles of 5-fluorouracil (1,000 mg/m2 at day #1-5) and cisplatin (60 mg/m2 at day #1) at 3 weeks interval. All H & E stained cervical cancer tissue slides were scored for apoptotic index and observed for microscopic changes of tumor cells by a pathologist. RESULTS: After the first cycle of chemotherapy, AI was significantly increased (from 2 times to 8 times). And widespread injury to cytoplasm was observed and followed by karyorrhexis and karyolysis of nucleus of tumor cells. The size of tumor nests was reduced and it was also noted that fibrosis and infiltration of inflammatory cells were increased. The parts of tumor nests were replaced by mature squamous cells and the changes in nuclear morphologic features pointing in a more differentiated direction. But after the second cycle of chemotherapy, only one patient showed an increase in AI by 1.2 times over that after the first cycle of chemotherapy. The rest showed slight decreases in AI compared to that after the first cycle of chemotherapy. In addition, fewer microscopic morphologic changes of tumor cells induced by chemotherapy were observed after the second cycle of chemotherapy compared to those after the first cycle of chemotherapy. CONCLUSION: We found that AI hardly increased or rather decreased, and that microscopic changes of tumor cells were fewer after the second cycle of neoadjuvant chemotherapy compared to the situation after the first cycle of chemotherapy. Thus, we could deduce that chemoresistance might rapidly develop in cervical cancer cells after the first cycle of neoadjuvant chemotherapy using 5-fluorouracil and cisplatin. So we need to consider this problem when we treat the locally advanced cervical cancer patients with neoadjuvant chemotherapy using 5-fluorouracil and cisplatin.

A case of collagenous colitis presented with chronic diarrhea and hypokalemia / 대한내과학회지

Collagenous colitis is recognized as one of the causes of chronic diarrhea accompanied with autoimmune diseases. It is a disease associated with chronic watery diarrhea and typical histologic findings of a thick subepithelial collagenous deposit on biopsy. We experienced a 75-year-old man patient with chronic watery diarrhea and mild abdominal pain for 7 years. Physical examination, laboratory and radiologic studies were unremarkable except hypokalemia. Colonoscopy disclosed mucosal atrophy, loss of submucosal vessel and altered vascularity of terminal ileum, ascending colon. Colonoscopic biopsy revealed homogenous hyaline layered collagen deposition beneath the surface epithelium and Masson's trichrome stain showed collagen deposition. We report the case of collagenous colitis with a review of literature.

Loss of PTEN Expression in Breast Cancers

Background : PTEN, located on chromosome 10q23.31, is a novel tumor suppressor gene. In the sporadic breast cancers, the incidence of the loss of heterozygosity of PTEN is approximately 10% to 40%, but the incidence of intragenic mutation of PTEN is less than 1%. To as- sess the role of the PTEN in the invasive ductal breast cancer, we studied the frequency of the loss of PTEN expression, its correlation with the commonly used prognostic factors of the breast cancer and with PTEN promoter hypermethylation status. Methods : Immunohistochemical staining with an anti-PTEN protein antibody was performed on the paraffin-embedded breast tissues from 129 women with a diagnosis of invasive ductal carcinoma. Methylation specific PCR was performed to detect hypermethylation in the PTEN gene on the 28 cases with the loss of PTEN expression. Results : Sixty-two (48%) of 129 breast tumors had the loss of PTEN expression. The loss of PTEN expression was correlated with lymph node metastasis and stage, and there was a near-significant correlation with the tumor size. PTEN promoter hypermethylation was found in five (18%) out of 28 patients. Conclusion : These results suggest that the loss of PTEN expression might play a role in the progression of the breast cancer and that the aberrant promoter methylation is one of the silencing mechanisms of PTEN.

RUNX3 Methylation Status in Colonic Carcinoma and Adenoma

BACKGROUND: RUNX3 is expressed throughout the luminal gastrointestinal tract. RUNX3 is on chromosome 1p36, a location considered to carry an important tumor suppressor for many types of cancers. Epigenetic silencing of RUNX3 is causally related to human gastric cancer. METHODS: Colorectal cancers, adenoma, and the corresponding normal mucosa were obtained from 26 individual patients. To identify methylation of RUNX3 in colonic carcinogenesis, methylation-specific PCR was performed. RESULTS: RUNX3 methylation was found in one case of colonic carcinoma. The normal mucosa and tubular adenoma of this case had no methylation. No other cases were found to have methylations. CONCLUSIONS: These results are very different from the findings of gastric carcinomas, where frequent DNA methylation in the vicinity of the RUNX3 promoter is found. Although, the possibility of a role of RUNX3 methylation in the colon can not be completely ruled out, these results suggest that methylation of the RUNX3 promoter region might not contribute to the adenoma-carcinoma sequence of the colon.

Effects of Calcitriol on Delayed Neuronal Damage of Hippocampus in Transient Global Ischemia Model of Mature Gerbil

BACKGROUND: It is well documented that calcium ions perform a major role in neuronal degeneration in cerebrovascular disease and the other degenerative diseases, and that 1,25-dihydroxyvitamin D3 (D3) has the dose-dependent protective effects. This study was performed to examine the effects of different D3 dosages against delayed neuronal damage of the hippocampus. METHODS: Mature mongolian gerbils were injected with either 0.8 microgram/kg/day (group 2) for 5 days or 1.0 microgram/kg/day for 8 days (group 3) prior to the 10 min ligation of the bilateral common carotid arteries. Immunohistochemical expression for the glial cell line-derived neurotrophic factor (GDNF), the basic fibroblast growth factor (bFGF) and the platelet-derived neurotrophic factor (PDNF) was observed in the D3-injected (0.8 microgram/kg/day for 5 days) group. RESULTS: Group 2 showed a highly significant attenuation of delayed neuronal damage in the lateral CA1 region at 7 days after reperfusion. Group 3 showed unilateral or bilateral hemispheric infarcts 24 h after the onset of reperfusion. The D3-injected group showed a markedly increased bFGF expression level. CONCLUSION: The dose-dependent effect of D3 suggests the importance of determining the appropriate D3 dose for clinical applications. Although the mechanism(s) of neuroprotection by D3 remains unclear, D3 may facilitate a reduction in ischemia-induced oxidative stress via the activation of the neurotrophic factors, including bFGF and GDNF.

Comparison of Ziehl-Neelsen Stain and TB-PCR on Detection of Mycobacterium tuberculosisin Formalin-fixed, Paraffin-embedded Tissues of Chronic Granulomatous Inflammation

BACKGROUND: TB-PCR is a faster and more sensitive method to detect mycobacterium than acid-fast bacilli (AFB) stain, which is laborious and time consuming. We compared the sensitivity and specificity of AFB stain and TB-PCR and examined the possibility of TB-PCR as a confirmative test without AFB stain in the diagnosis of tuberculosis. METHODS: We performed Ziehl-Neelsen stain and nested PCR using a commercially available TB-PCR kit amplifying IS6110 sequence in 81 cases of paraffin-embedded tissues diagnosed as chronic granulomatous inflammation. In addition, we evaluated the morphology of granuloma and the presence of caseation necrosis. RESULTS: Of the 81 cases studied, 22 (27.2%) and 40 (49.4%) were positive for AFB stain and TB-PCR, respectively. Of 49 cases accompanying caseation necrosis, 19 (38.8%) were AFB stain positive and 37 (75.5%) were TB-PCR positive; a result that is comparable with that of other reports. Of the 22 AFB-positive cases, 2 were TB-PCR negative. CONCLUSION: TB-PCR is very helpful for the diagnosis of tuberculosis in routinely processed, formalin-fixed, paraffin-embedded tissue samples. Nevertheless, AFB stain should continue to be performed at the same time.

A Case of Primitive Neuroectodermal Tumor of the Uterus / 대한산부인과학회잡지

Primitive neuroectodermal tumor (PNET) is a rare tumor derived from fetal neuroectodermal cells. These tumors occur in the central nervous system and peripheral locations, but the occurrence of primitive neuroectodermal tumors located in the uterus is extremely rare. We present a 53-year-old woman with primitive neuroectodermal tumor of the uterus confirmed by immunohistochemical staining. We have experienced one case of PNET of the uterus and wish to report with brief review of concerned literature.

Remission of Intractable Diarrhea in Secondary Amyloidosis Associated with Rheumatoid Arthritis / 대한류마티스학회지

Intractable diarrhea associated with secondary amyloidosis in rheumatoid arthritis (RA) is a serious clinical entity with poor prognosis. We describe a 39-year-old male RA patient who presented with intractable diarrhea. Biopsy findings of terminal ileum and colon revealed amyloidosis secondary to RA. Effective treatment of rheumatoid arthritis resulted in remission of intractable diarrhea caused by amyloid protein deposition.

The Expression of Vascular Endothelial Growth Factor, Platelet-Derived Growth Factor and Intercellular Adhesion Molecule in Severe Preeclamptic Placenta / 대한산부인과학회잡지

OBJECTIVE: To determine the expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and intercellular adhesion molecule (ICAM-1) in placenta from pregnancies complicated by severe preeclampsia and normal pregnancies. METHODS: Placental tissues were obtained from 10 normotensive pregnancies (control group) and 20 severe preeclamptic pregnancies (preeclamptic group). Immunohistochemical staining of placental tissue was used to determine tissue expression of VEGF, PDGF and ICAM-1. The intensity of staining was evaluated by scoring as 0, 1, 2 and 3. RESULTS: Immunolocalization of VEGF and PDGF was significantly observed in the syncytotrophoblast with less intense staining in intravillous stromal cells and intravillous endothelial cells of fetal vessels in preeclamptic group. There were no differences in immunolocalization of staining in control group. Intensity of VEGF and PDGF immunostaining in syncytotrophoblast was significantly increased in preeclamptic group. However, immunolocalization and the intensity of ICAM-1 staining were not significantly different in both groups. CONCLUSION: The expression of VEGF and PDGF in the syncytotrophoblast was significantly up-regulated in severe preeclamptic placenta. These up-regulation of VEGF and PDGF might reflect that placental ischemia and hypoxic state in severe preeclampsia induce VEGF and PDGF in the syncytotrophoblasts of placenta. However the unchanged pattern of ICAM-1 expression in severe preeclampsia suggests that ICAM-1 is unlikely to be a factor by which the adverse pregnancy outcome arises in severe preeclampsia.

KAI-1 Protein Expression in Breast Cancer: Correlation with Axillary Lymph Node Metastasis and other Prognostic Factors

BACKGROUND: KAI-1 is a metastasis suppressor gene. We have evaluated the correlationbetween KAI-1 protein expression in ductal carcinomas of the breast and axillary lymph nodemetastasis. METHODS: The expression of KAI-1 protein was confirmed by immunohistochemistryto examine breast tissues of ductal carcinomas from 50 patients with nodal metastasisand from 53 patients without metastasis. Western blot analysis was performed on fresh frozenbreast tissues from 17 cases with nodal metastasis and from 19 cases without metastasis. RESULTS: Immunohistochemical KAI-1 protein expression was decreased or negative in 39out of 50 cases with metastasis (78%), compared with 8 out of 53 cases with no metastasis(15.1%). The difference was statistically significant (p<0.05). Immunohistochemical KAI-1protein expression was significantly decreased in cases with higher modified Black's nucleargrade (p=0.027) and larger tumor size (p=0.039). Western blot analysis showed positivebands at 29.5 kDa in 8 out of 19 cases without metastasis (42.1%), and none of the 17 caseswith metastasis showed positive bands (p=0.0024). CONCLUSION: These results suggest thepossibility that KAl-1 might play a major role of a metastasis suppressor gene in addition tothe part it plays in the growth and progression of human breast ductal carcinoma. In addition, the decreased expression of KAI-1 protein in breast ductal carcinomas could be used as afactor suggesting poor prognosis.

The Prognostic Significance of the Overexpression of HER-2/ neu in Korean Gastric Carcinomas and the In Vitro Effects of Anti-HER-2/neu Antibody on Cell Growth in the Gastric Carcinoma Cell Lines / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor (EGFR) and shares intrinsic tyrosine kinase activity. The HER2 gene has been found to be amplified in various human cancers and to be associated with poor prognosis. The authors investigated the correlation between clinicopathologic factors and the overexpression of the p185(HER2) in Korean gastric adenocarcinoma patients, and determined whether the antiproliferative effects of anti- p185(HER2) antibody can also be observed on gastric cancer cell lines that overexpress this growth factor receptor. MATERIALS AND METHODS: We evaluated the relationship between p185(HER2) overexpression and clinicopathological features in 94 (M: F=52: 42) gastric adenocarcinoma patients (median age 59 years). Protein expression was analysed by immunohistochemical staining in paraffin embedded tissues with monoclonal antibody for p185(HER2). To explore the role of humanized anti-p185(HER2) monoclonal antibody trastuzumab (Herceptin ) in vitro, the growth curve of Korean gastric cancer cells that overexpress the p185(HER2) protein was studied and a cell cycle analysis was performed. RESULTS: p185(HER2) overexpression correlates positively with lymph node metastasis (p=0.002), distant metastasis (p=0.01), AJCC classification (p=0.01), higher relapse rate p=0.001), and a tendential association with the pT stage (p=0.054). p185(HER2) overexpression was found to be more frequent in advanced gastric cancer than early gastric cancer (54.1% vs 24.2%, p=0.008). Patients with overexpression of p185(HER2) were found to have significantly lower relapse-free (p=0.003) and overall survival (p= 0.0004) than patients without overexpression. Among several Korean gastric cancer cell lines, SNU-1, SNU-5, and SNU-620 overexpress p185(HER2). Trastuzumab inhibited the proliferation of p185(HER2) overexpressed Korean gastric cancer cell line by 21% with down-regulation of p185(HER2) protein expression. DNA fluorescence flow cytometry of propidium iodide-stained nuclei showed a reduction in the fraction of the S phase following treatment with trastuzumab. CONCLUSIONS: Taken together, our observations suggest the potential prognostic significance of p185(HER2) overexpression in Korean gastric adenocarcinoma patients and point to the need for further research on this mechanism. This suggests the possible use of p185(HER2) as a therapeutic target in gastric cancer.