Biomarker analysis in stage III-IV (M0) gastric cancer patients who received curative surgery followed by adjuvant 5-fluorouracil and cisplatin chemotherapy: epidermal growth factor receptor (EGFR) associated with favourable survival.

The aim of this study was to analyse the impact of epidermal growth factor receptor (EGFR), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), aurora kinase (ARK) A/B, and excision repair cross-complementing gene 1 (ERCC1) on the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin (FP) after curative gastric resection. Normal and cancer tissue were separately obtained from gastrectomy samples of 153 patients with AJCC stage III-IV (M0) who subsequently treated with adjuvant FP chemotherapy. TS, DPD, TP, ERCC1, and ARK proteins were measured by immunohistochemistry (IHC). EGFR expression was investigated using a standardized IHC with the EGFR PharmDx assay. Amplification of EGFR gene was analysed using fluorescent in situ hybridisation (FISH). In multivariate analysis, stage, ratio of positive to removed lymph nodes, and EGFR expression were significant prognostic factors for overall survival. Patients with higher EGFR expression had better overall survival than those with lower expression (relative risk: 0.475 (95% confidence interval, 0.282-0.791, P=0.005). Low EGFR expression might be a predictive marker for relapse in curative resected stage III-IV (M0) gastric cancer patients who received adjuvant FP chemotherapy.

Sentinel node biopsy for cT1 and cT2a gastric cancer.

AIMS: To evaluate the feasibility and accuracy of sentinel node (SN) biopsy for gastric cancer. PATIENTS AND METHODS: One hundred patients with gastric cancer diagnosed as cT1 (n=80) or cT2a (n=20) were enrolled. Indocyanine green-stained SNs were analysed by hematoxylin and eosin staining (n=100) and by cytokeratin immunohistochemistry (n=50). RESULTS: SNs were identified in 94 of the 100 patients and the mean number of SNs was 4.4 (range, 1-12). Of these 94 patients, 14 patients had lymph node metastases. Two patients with T1 and one patient with T2 had metastases in non-SNs alone by hematoxylin and eosin staining (diagnostic accuracy =97.3% in T1 and 95.0% in T2). All three patients with a false negative result had a tumour, which was more than 4 cm in size and signet ring cell histology. In two of them, the tumour was located at lesser curvature. By immunohistochemical staining, three patients with T1 and one patient with T2 were found to have lymph node micrometastases in non-SNs alone among 45 patients (diagnostic accuracy =92.1% in T1, 85.7% in T2). CONCLUSION: SN biopsy using indocyanine green can be performed rapidly and easily with a high detection rate and accuracy in patients with T1 gastric cancer. However, it should be performed with caution for large tumours with a signet ring cell histology located at lesser curvature due to the possibility of a false negative result.

MDR1 gene expression: its effect on drug resistance to doxorubicin in human hepatocellular carcinoma cell lines.

BACKGROUND: Hepatic tumors are resistant to many chemotherapeutic agents. Although elevated MDR1 (also known as PGY1) gene expression has been shown in such tumors, no direct association has been established between the gene expression and multidrug resistance. PURPOSE: To evaluate the role of the MDR1 gene in the drug resistance of hepatoma, we tested nine human hepatoma cell lines for their expression of the MDR1 gene. METHODS: We measured the MDR1 messenger RNA (mRNA) expression by RNA slot-blot analysis and by immunocytochemical staining with a P-glycoprotein-specific monoclonal antibody, MRK16. The in vitro chemosensitivity of these cell lines to fluorouracil, doxorubicin, mitomycin C, cisplatin, and etoposide (VP-16) was determined using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colorimetric assay. For doxorubicin cytotoxicity, we also tested the potentiating effect of several multidrug resistance-reversing agents. RESULTS: Slot-blot analysis and immunocytochemistry showed that two cell lines expressed high levels of MDR1 mRNA, one expressed an intermediate level, and all others were low expressors. The MTT assay results showed that all cell lines tested were generally resistant to chemotherapeutic agents. The assay area under the curve (AUC) was within a clinically achievable range only for VP-16 in one of nine cell lines. When the IC50 values were compared among the cell lines, the results revealed a close association with the MDR1 gene expression only for doxorubicin resistance. Verapamil and quinidine lowered the IC50 values of doxorubicin for MDR1-positive cell lines. The lowered assay AUC levels for both reversing agents, however, were still higher than the clinically achievable range. CONCLUSION: These results indicate that the MDR1 gene probably has a role in doxorubicin resistance in hepatocellular carcinoma and that the resistance can be overcome by some multidrug resistance-reversing agents. IMPLICATIONS: Some widely used anticancer agents might be ineffective for treating hepatocellular carcinoma in clinical situations even when combined with reversing agents.

The timing and characterization of p53 mutations in progression from atypical ductal hyperplasia to invasive lesions in the breast cancer.

The main reason for the recent interest in p53 is that almost 50% of human cancers contain p53 gene mutations. The majority of studies on p53 alterations in breast cancer have been limited to the isolated cases of ductal carcinoma in situ and infiltrating ductal carcinoma. The aims of this study were to determine the status and timing of p53 mutation in the progression from atypical ductal hyperplasia to invasive cancer, and to evaluate the patterns of p53 mutations in noninvasive and invasive lesions. Available lesions of invasive (n=88) and noninvasive (n=76) lesions were microdissected in 107 paraffin-embedded tissues (19 ductal carcinomas in situ, 57 invasive carcinomas with intraductal components, and 31 pure invasive carcinomas) and double-strand DNA sequencing was performed in exon 4-9 of the p53 gene. Among in situ cancers without invasive disease 36.8% had p53 mutations whereas in situ cancer with concurrent invasive disease showed p53 mutations in 33.3% of cases. In particular, two of seven atypical ductal hyperplasias harbored p53 alterations (one insertion and one missense mutation) in exon 8. The invasive component harbored p53 mutations in 30 of 88 cases (34.1%). We also discovered a novel deletion of 14 bp in exon 6 of two invasive lesions. The invasive component (1.33+/-0.13) carried a greater number of p53 mutations than its counterparts (1.19+/-0.10) and demonstrated more frequent multiple mutations (23.3% vs. 15.4%), but without statistical significance. Moreover, no statistical significance could be attached to the mutation frequency in the zinc-binding domains (26.7% vs. 15.4%), the directly DNA contact region (13.3% vs. 15.4%) and the missense mutation of p53 (50.0% vs. 57.7%) of the two groups. Based on our results, in spite of the small number of the lesions investigated, p53 mutation can occur at the stage of atypical ductal hyperplasia. The hypermutability and the specific p53 mutations involving the biologically functional domain (e.g., zinc binding domain or DNA contact region) have an insignificant influence on invasive progression in the breast cancer.

Intraoperative gastroscopy for gastric surgery.

BACKGROUND: Few reports are available on the use of intraoperative gastroscopy for gastric surgery. METHODS: The details of 33 patients (25 early gastric cancers and eight gastric submucosal tumors) who underwent intraoperative gastroscopy from June 2003 to June 2004 were analyzed. The type of operation or resection margin was determined by evaluating both sides of the stomach simultaneously by combined operative and gastroscopic methods. RESULTS: Preoperative endoscopic clipping was done preferentially for early gastric cancer. However, when precise localization was needed, intraoperative gastroscopy was used. Curative gastric resection was possible in 25 early gastric cancer patients after accurate lesion localization. Laparoscopic wedge resections of submucosal tumors were performed in seven patients without stenosis by combined laparoscopic and gastroscopic methods. CONCLUSIONS: Intraoperative gastroscopy can be used effectively during gastric surgery for early gastric cancer or submucosal tumors and can be regarded as a modern stethoscope to gastric surgeons.

Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk.

To evaluate the potential association between GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a South Korean study population consisting of 189 histologically confirmed incident breast cancer cases and their 189 age-matched control subjects with no present or previous history of cancer. A multiplex polymerase chain reaction method was used for the genotyping analyses and statistical evaluations were performed by unconditional logistic regression model. The GSTM1 null genotype was significantly associated with breast cancer risk in premenopausal women [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1-3.7], but not in the postmenopausal women (OR = 0.9, 95% CI = 0.5-1.9), nor in all women grouped together (OR = 1.3, 95% CI = 0.8-1.1). The GSTT1 null genotype posed a similar risk of breast cancer with an OR of 1.6 (95% CI = 1.0-2.5) for the total breast cancer group, OR of 1.7 (95% CI = 0.9-3.2) for pre-menopausal women, and OR of 1.3 (95% CI = 0.6-2.8) for post-menopausal women. The breast cancer risk associated with concurrent lack of both GSTM1 and GSTT1 genes was 2.2 (95% CI = 1.1-4.5), and the risk increased as the number of null genotype increased (P for trend = 0.03). When the data were stratified by the known risk factors of breast cancer, a significant interaction was observed between the GSTM1 genotypes and alcohol consumption (P for interaction = 0.03). An especially remarkable risk of breast cancer was observed for alcohol-consuming premenopausal women lacking both the GSTM1 and GSTT1 genes (OR = 5.3, 95% CI = 1.0-27.8) compared to those with both of the genes. Our findings thus suggest a novel gene-environment interaction which plays an important role in the individual susceptibility to breast cancer. p6

Relationship between the Val158Met polymorphism of catechol O-methyl transferase and breast cancer.

A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the risk of breast cancer in Korean women. One hundred and sixty-three histologically confirmed incident breast cancer cases and 163 age- and menopausal status-matched control individuals with no present or previous history of cancer were selected as study subjects. COMT genetic polymorphism was determined by gel electrophoresis after NlaIII enzyme digestion of amplified DNA. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression after adjustment for known or suspected risk factors of breast cancer. Women with at least one COMT lower enzyme activity associated allele (COMT-L) were at elevated risk for breast cancer (OR = 1.7, 95% CI = 1.04-2.78) compared with those homozygous for high enzyme activity associated COMT-H alleles. Among women with low (> or = 23.1) body mass index the COMT-L allele containing genotypes posed a marginally significant increased risk of breast cancer compared to the COMT-HH genotype (OR = 1.8, 95% CI = 0.95-3.48). Women with at least one COMT-L allele who had experienced a full-term pregnancy when aged over 30 years or were nulliparous had 2.7-fold increased risk; however, this increase did not reach statistical significance (OR = 2.7, 95% CI = 0.64-11.35). Furthermore, never-drinking and never-smoking women with at least one COMT-L allele were at increased risk of breast cancer compared to those with COMT-HH genotype with ORs of 2.0 (95% CI = 1.23-3.38) and 1.7 (95% CI = 1.04-2.62), respectively. These results are consistent with studies showing that COMT genotype of lower enzyme activity might be related to increase in risk of breast cancer, and extend this finding to Korean women.

Microcystic adenomas of the pancreas. Report of three cases with two of multicentric origin.

Three cases of microcystic adenomas of the pancreas with special reference to multicentric origin are described. The gross features and light microscopic findings were consistent with those described as being microcystic adenomas, but in two cases the gross examination and gelatin-embedded giant slices revealed multiple, isolated development of tumors ranging from submacroscopic nodules to tumors 4.5 cm in diameter. The larger tumors often showed ragged margins with small satellite nodules around the masses. A central fibrolamellar stellate core with centrifugally radiating septation was found in most of the tumor masses, even in the smaller ones. Ultrastructural and immunohistochemical findings revealed a single row of glycogen-rich epithelial cells, but participation of myoepithelial cells was not confirmed. Instead, vimentin-positive cells (pericytes) within the interstitial space incorporated closely with the basal lamina of the cyst wall. This study suggests that a small percentage of microcystic adenomas of the pancreas develop in multiple tumors, and some appear as a single tumor by their confluence.

Cyclin E overexpression as an independent risk factor of visceral relapse in breast cancer.

AIM: Prognostic value of the cyclin E overexpression in breast cancer has not been clearly established, especially in relation to the pattern of recurrence. We investigated the implication of cyclin E overexpression for the pattern of recurrence in Korean breast cancer patients. METHODS: Using immunohistochemical methods, we retrospectively examined the cyclin E expression level in breast cancer specimens from 128 women who underwent curative breast surgery, and correlated the levels of expression with the pattern of relapse in patients. RESULTS: Cox model-based multivariate analysis indicated that distant relapse could be predicted by the number of positive axillary lymph nodes, high cyclin E expression, and the younger age (<35 years) of the patient. We tested further the association of cyclin E overexpression with the specific types of recurrence; multivariate analyses indicated that adjusted relative risks of bone and visceral relapse as the first events among high cyclin E group were 2.46 (95% confidence interval (CI), 0.86-7.02) (P=0.092), and 3.98 (95% CI, 1.23-12.94) (P=0.022), respectively. On the other hand, cyclin E overexpression was not associated with the risk of locoregional relapse. CONCLUSION: Our data suggest that cyclin E overexpression in primary breast carcinoma tissue could independently predict the risk of distant relapse, especially of visceral relapse, as the first failure after curative breast surgery.

Mutation of ras oncogene in gastric adenocarcinoma: association with histological phenotype.

In order to explore the role of ras oncogene in gastric carcinomas from Korean patients, we examined the frequency of point mutations all three ras oncogenes (Ki-, Ha-, and N-ras). A total of 57 DNA samples were prepared from 3 gastric carcinoma cell lines, 10 malignant ascites, and 44 frozen gastric tumor tissues. Exons 1 and 2 of each ras oncogene were amplified by polymerase chain reaction (PCR), and analyzed by single strand conformation polymorphism (SSCP) and direct sequencing. Mutated ras genes were detected in 6 out of 57 samples (10%). One cell line and 2 tumors showed a mutation at exon 1 of Ki-ras. N-ras mutations were also detected at exon 1 of 3 tumors. Histologically, all the ras mutation cases exhibited a diffuse phenotype. In summary, we performed a comprehensive analysis to investigate the mutation of all three ras oncogenes in gastric carcinoma. The results demonstrate infrequent mutations of Ki- and N-ras which may favor the development of diffuse type gastric carcinomas, implicating a different genetic pathway in diffuse and intestinal type gastric carcinomas.

Expression of phospholipase C-gamma 1 and its transcriptional regulators in breast cancer tissues.

BACKGROUND: PLC-gamma 1 is activated through direct interaction with growth factor receptor tyrosine kinase but little is known about the mechanisms controlling PLC-gamma 1 expression and its biological significance. MATERIALS AND METHODS: Using immunoblotting, we evaluated PLC-gamma 1 protein overexpression in twenty breast cancer tissues. The expression of binding protein to GES1, GES2 and GES3, located in transcriptional regulator (GPE1) was found by electrophoretic mobility shift assay (EMSA). We also determined whether there was any correlation between prognostic factors (numbers of metastatic axillary nodes, histologic grade, c-erbB2, p53, and E-cadherin) and the overexpression of PLC-gamma 1 protein. RESULT: On immunoblotting, 17 of 20 breast cancer tissues showed overexpression of PLC-gamma 1, a result of which was corresponded to that of immunohistochemistry. The binding proteins to GES1, GES2 and GES3 were overexpressed only when PLC-gamma 1 protein overexpression was apparent. Positive expression of E-cadherin only was significantly associated with PLC-gamma 1 protein overexpression (x = 0.607, p = 0.045). CONCLUSION: GPE1 binding proteins might be the transcriptional regulator in PLC-gamma 1 overexpression and the relationship between expression of PLC-gamma 1 and E-cadherin would require further elucidation.

Predictors of operative morbidity and mortality in gastric cancer surgery.

BACKGROUND: The aim of this study was to identify factors that predict morbidity and mortality in gastric cancer surgery. METHODS: Data on 719 consecutive patients who underwent operations for gastric cancer at Seoul National University Hospital between January and December 2002 were reviewed. RESULTS: Overall morbidity and mortality rates were 17.4 per cent (125 patients) and 0.6 per cent (four patients) respectively, and the rates of surgical and non-surgical complications were 14.7 per cent (106 patients) and 3.3 per cent (24 patients). Morbidity rates were higher in patients aged over 50 years (odds ratio (OR) 1.04 (95 per cent confidence interval (c.i.) 1.02 to 1.06)), when the gastric tumour was resected with another organ (36 per cent for combined resection versus 15.4 per cent for gastrectomy only; OR 3.25 (95 per cent c.i. 1.76 to 6.03)) and when gastrojejunostomy was used for reconstruction after subtotal gastrectomy (17.0 per cent for Billroth II versus 9.5 per cent for Billroth I; OR 2.00 (95 per cent c.i. 1.05 to 3.79)). Only three patients (2.8 per cent) with a surgical complication underwent reoperation, two for adhesive obstruction and one for intra-abdominal bleeding. CONCLUSION: Age, combined resection and Billroth II reconstruction after radical subtotal gastrectomy were independently associated with the development of complications after gastric cancer surgery.

Biologic behavior and treatment of intransit metastasis of melanoma.

The therapeutic approach to intransit metastasis of melanoma has been surveyed in 52 patients admitted to this institute during the past ten years with a clinical history of intransit lesions of melanoma. Ten of these patients have been long term survivors. Two additional patients died at 23 and 28 months, respectively, after surgical removal of the lesions, and at autopsy, no evidence of recurrence was noted. All long term survivors belong to the group of 35 patients that received intensive local management, while all 17 patients given systemic chemotherapy or immunotherapy only died from progression of the disease. Every trial of system chemotherapy or system immunotherapy, aiming to control these lesions of intransit metastasis, failed. Systemic chemotherapy or systemic immunotherapy should not be used alone in the treatment of intransit metastasis. Such regional modalities as hyperthermic perfusion, local immunotherapy or excisions of wide strips of skin, subcutaneous fat and fascia around these lesions, in addition to systemic treatment, should be utilized persistently.

Macrocystic serous cystadenoma of pancreas--a case report.

The macrocystic variant of serous cystadenomas of the pancreas has only recently been described. We present a case of a 40 year-old female, who presented with vague indigestion. The cyst was unilocular, and was lined by simple cuboidal, ciliated serous type epithelium. Fine needle aspiration, immunohistochemical, light microscopic, and electron microscopic studies are discussed.

A case of unilocular hydatid disease imported from Saudi Arabia.

A 39-year-old Korean man with general malaise was found to have two hepatic cysts by computed tomography. He had the history of close contact with domesticated wild dog in Saudi Arabia in 1976. Two cysts, 15cm and 10cm in diameter which contained clear fluid, were excised from both lobes of the liver. He was pathologically diagnosed as unilocular hydatid disease. This case is regarded as an imported case from Saudi Arabia.

Abnormal expression of four novel molecular markers represents a highly aggressive phenotype in breast cancer. Immunohistochemical assay of p53, nm23, erbB-2, and cathepsin D protein.

BACKGROUND: In view of the cumulative results to date, p53, nm23, erbB-2, and cathepsin D are the most promising investigational prognostic factors in breast cancer. OBJECTIVES: The clinical utility of these molecular markers to predict recurrence was evaluated. METHODS: Archival pathology tissues of 100 breast cancer patients were analyzed by immunohistochemical assay. Molecular biologic data were merged with clinicopathologic variables. RESULTS: Thirty-two patients (32%) had recurrence of disease at a median follow-up of 48 months (range 26-72 months). Investigational factor expression had statistical correlation for recurrence with increasing coexpression: one variable 20.6%, two variables 34.2%, three variables 47.1%, four variables 80.0% (P = 0.003). In univariate analysis, lymph node metastasis, tumor size, erbB-2 protein overexpression, and loss of nm23 protein expression were significant variables to determine recurrence; in multivariate analysis, node status and tumor size emerged as the most significant variables for recurrence. CONCLUSIONS: Coexpression of the studied investigational variables functioned as significant prognostic correlates for recurrence. These findings suggest that the studied investigational prognostic factors possess the ability to discriminate a highly aggressive phenotype in breast cancer.

Prognostic factors in 2230 Korean colorectal cancer patients: analysis of consecutively operated cases.

To define the prognostic factors in Korean colorectal cancer patients, univariate and multivariate analysis were performed on data from 2230 consecutive patients who underwent resection for colorectal cancer at the Seoul National University Hospital. The prognostic variables used for the analysis included patient's age, gender, bowel obstruction, bleeding, symptom duration, preoperative leukocyte count, preoperative serum carcinoembryonic antigen (CEA) level, Dukes' stage, tumor location, tumor size, depth of bowel wall invasion, number of lymph node metastases, histologic differentiation, and gross morphology of tumor. The overall 5-year survival rate was 62%. In the univariate analysis, all the factors except sex, symptom duration, and tumor size were associated with prognosis. Among the factors significant in the univariate analysis, Dukes' stage (p < 0.001), number of lymph node metastasis (p < 0.001), CEA level (p < 0.001), tumor location (p = 0.003), gross morphology of tumor (p = 0.017), and depth of bowel wall invasion (p = 0.031) were significant in the multivariate analysis. Several differences in prognostic factors between colon cancer and rectal cancer were observed. In the multivariate analysis, gross tumor morphology was significant only for colon cancer, and histologic differentiation was significant only for rectal cancer. Lymph node metastasis was an independent prognostic variable for both colon and rectal cancer, but its significance was more prominent for rectal cancer. Although Dukes' stage is the most reliable prognostic predictor, this study shows that other factors (preoperative CEA level, gross morphology of tumor, location of tumor, nodal status) also provide important information for the outcome of the patient.

Influence of the number of lymph nodes examined on staging of gastric cancer.

BACKGROUND: Nodal staging for gastric cancer according to the 1997 Union Internacional Contra la Cancrum tumour node metastasis classification is based on the number of metastatic lymph nodes. The aim of this study was to evaluate whether the number of lymph nodes examined affected staging of gastric cancer. METHODS: A retrospective study was performed in 4789 consecutive patients with gastric cancer, who had undergone curative resection (R0) from 1986 to 1995. Patients were classified according to the number of nodes examined. The number of metastatic lymph nodes and stage-stratified survival were compared. RESULTS: There were significant differences in the number of metastatic lymph nodes and survival in stage IIIA between patients with 15 or more lymph nodes and those with fewer than 15 nodes. In analysis restricted to patients with 15 or more nodes, stage-stratified survival did not vary significantly with lymph node yields for any stage except IIIB, in which there was a significant difference between the subgroup with fewer than 20 examined lymph nodes and patients with 35 or more nodes. CONCLUSION: The number of lymph nodes examined did not significantly affect node staging of gastric cancer as long as at least 15 nodes were examined. For stage IIIB, more than 15 lymph nodes may be required for optimal staging.

Flow cytometric analysis of primary tumors and their corresponding metastatic nodes in breast cancer.

Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from one which is indolent to one which rapidly progresses. Although it is the metastasis rather than the primary tumor that ultimately overwhelms the patients, studies concerning the DNA pattern have focused on the primary tumors. This study was undertaken to identify heterogeneities between primary tumors and metastases, and to evaluate the prognostic significance of the ploidy pattern and the S-phase fraction (SPF) of metastatic nodes in axillary node positive patients. Seventy-four frozen specimens of the primary and corresponding metastatic nodes from 37 patients have been analyzed by flow cytometry and the SPF calculated. The results of ploidy pattern analysis in primaries revealed 25 diploidy (67.6%) and 12 aneuploidy (32.4%), while those in metastasis showed 17 diploidy (46.0%) and 20 aneuploidy (54.0%). The aneuploidy group in metastatic nodes had the poorer histological grade (85.0% vs. 15.0%, p = 0.02), and more mean metastatic nodes (5.75 +/- 2.10 vs. 3.05 +/- 1.56, p = 0.018), and more frequent lymphatic vessel invasion (65.0% vs. 11.8%, p = 0.031) than its counterpart. Decreased expression of ER (70.6% vs. 25.0% p = 0.006) and increased expression of c-erbB2 (65.0% vs. 23.5%, p = 0.012) were observed in the aneuploidy of metastatic nodes. The group with higher SPF in metastatic nodes had more metastatic nodes (5.47 +/- 2.31 vs. 4.00 +/- 1.78, p = 0.042), and the higher incidence of lymphatic vessel invasion (57.9% vs. 22.2%, p = 0.027), and poor histological grade (71.4% vs. 37.5%, p = 0.039). In conclusion, the cell populations in metastatic nodes revealed DNA pattern which differed from that of primary tumors. The ploidy pattern and SPF in metastatic nodes might be considered as discriminate measure for risk factors in breast cancer patients with positive axillary node.