Interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma

Background@#The accurate pathologic diagnosis and subtyping of high-grade endometrial carcinoma are often problematic, due to its atypical and overlapping histopathological features. @*Methods@#Three pathologists reviewed 21 surgically resected cases of advancedstage endometrial carcinoma. The primary diagnosis was based only on hematoxylin and eosin stained slides. When a discrepancy arose, a secondary diagnosis was made by additional review of immunohistochemical (IHC) stains. Finally, three pathologists discussed all cases and rendered a consensus diagnosis. @*Results@#The primary diagnoses were identical in 13/21 cases (62%). The secondary diagnosis based on the addition of IHC results was concordant in four of eight discrepant cases. Among four cases with discrepancies occurring in this step, two cases subsequently reached a consensus diagnosis after a thorough discussion between three reviewers. Next-generation sequencing (NGS) study was performed in two cases in which it was difficult to distinguish between serous carcinoma and endometrioid carcinoma. Based on the sequencing results, a final diagnosis of serous carcinoma was rendered. The overall kappa for concordance between the original and consensus diagnosis was 0.566 (moderate agreement). @*Conclusions@#We investigated stepwise changes in interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma. We demonstrated the utility of IHC and NGS study results in the histopathological diagnosis of advanced-stage endometrial carcinoma.

Surgical manual of the Korean Gynecologic Oncology Group: classification of hysterectomy and lymphadenectomy / 부인종양

The Surgery Treatment Modality Committee of the Korean Gynecologic Oncologic Group (KGOG) has determined to develop a surgical manual to facilitate clinical trials and to improve communication between investigators by standardizing and precisely describing operating procedures. The literature on anatomic terminology, identification of surgical components, and surgical techniques were reviewed and discussed in depth to develop a surgical manual for gynecologic oncology. The surgical procedures provided here represent the minimum requirements for participating in a clinical trial. These procedures should be described in the operation record form, and the pathologic findings obtained from the procedures should be recorded in the pathologic report form. Here, we focused on radical hysterectomy and lymphadenectomy, and we developed a KGOG classification for those conditions.

The Usefulness of Intraoperative Circumferential Frozen-Section Analysis of Lumpectomy Margins in Breast-Conserving Surgery / 한국유방암학회지

PURPOSE: Intraoperative frozen-section analysis of the lumpect-omy margin during breast-conserving surgery (BCS) is an excellent method in obtaining a clear resection margin. This study aimed to investigate the usefulness of intraoperative circumferential frozen-section analysis (IOCFS) of lumpectomy margin during BCS for breast cancer, and to find factors that increase the conversion into mastectomy. METHODS: From 2007 to 2011, 509 patients with breast cancer underwent IOCFS during BCS. The outer surfaces of the shaved lumpectomy margins were evaluated. A negative margin was defined as no ink on the tumor. All margins were evaluated using the permanent section analysis. RESULTS: Among the 509 patients, 437 (85.9%) underwent BCS and 72 (14.1%) finally underwent mastectomy. Of the 483 pathologically confirmed patients, 338 (70.0%) were true-negative, 24 (5.0%) false-negative, 120 (24.8%) true-positive, and 1 (0.2%) false-positive. Twenty-four patients (4.7%) among total 509 patients had undetermined margins as either atypical ductal hyperplasia or ductal carcinoma in situ in the first IOCFS. The IOCFS has an accuracy of 94.8% with 83% sensitivity, 99.7% specificity, 93.4% negative predictive value, and 99.2% positive predictive value. Sixty-three cases (12.4%) were converted to mastectomy, the first intraoperatively. Of the 446 (87.6%) patients who successfully underwent BCS, 64 patients received additional excisions and 32 were reoperated to achieve clear margin (reoperation rate, 6.3%). Twenty-three of the reoperated patients underwent re-excisions using the second intraoperative frozen section analysis, and achieved BCS. Nine cases were additionally converted to mastectomy. No significant differences in age, stage, and biological factors were found between the BCS and mastectomy cases. Factors such as invasive lobular carcinoma, multiple tumors, large tumor, and multiple excisions increased the conversion to mastectomy. CONCLUSION: The IOCFS analysis during BCS is useful in evaluating lumpectomy margins and preventing reoperation.

Neuroendocrine Tumors of the Female Reproductive Tract: A Literature Review

Neuroendocrine tumors of the female reproductive tract are a heterogeneous group of neoplasms that display various histologic findings and biologic behaviors. In this review, the classification and clinicopathologic characteristics of neuroendocrine tumors of the female reproductive tract are described. Differential diagnoses are discussed, especially for non-neuroendocrine tumors showing high-grade nuclei with neuroendocrine differentiation. This review also discusses recent advances in our pathogenetic understanding of these disorders.

Liquid-Based Pap Smear Findings of Uterine Cervical Lymphoma: Three Cases Report

Malignant lymphoma of the uterine cervix is rarely diagnosed by cytology because it presents as a subepithelial mass. We report three cases of diffuse large B-cell lymphoma in the uterine cervix with a description of liquid-based pap smear (LBP) findings. All patients were presented with cervical masses, but a suspicion of malignant lymphoma was made in only one case by preoperative LBP. The LBP of two cases showed several atypical lymphoid cells in a clear background. The other case revealed numerous atypical lymphoid cells in a necrotic background. Most tumor cells had an increased N/C ratio, round but focally irregular nuclei, coarse chromatin, and prominent nucleoli. Nuclear blebing, dimpling, and multi-lobulation were also found. Diagnosis of malignant lymphoma by LBP is usually more difficult than by conventional techniques, because of a sparse numbers of cells and the lack of necrotic background. However, well preserved morphological features and a better resolution of nuclear details could be the benefits of LBP.

Bilateral Frontal Polymicrogyria: An Autopsy Case Report

Bilateral frontal polymicrogyria is a recently recognized syndrome characterized by symmetric polymicrogyria of both frontal lobes that presents with delayed motor and language development, spastic quadriparesis, and variable mental retardation. However, the postmortem findings of this syndrome are not fully elaborated. Here we describe an autopsy case of bilateral frontal polymicrogyria in a male fetus delivered at 22 weeks gestation due to extensive chorioamnionitis. The microscopic findings included a thinned cortical plate with fair neuronal maturation. There were no signs of neuronal damage and the white matter was unremarkable.

Availability of Immunohistochemistry in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma

BACKGROUND: Making the diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) is often difficult, and there are no accurate immunohistochemical or molecular markers. The purpose of this study is to evaluate performing immunohistochemistry to make the diagnosis of FVPTC. METHODS: A total of 249 thyroid lesions were studied. We made the tissue microarray, and we assessed the expression of HBME-1, galectin-3, CD56, and p63. RESULTS: Galectin-3, HBME-1, and p63 were positive in 79.7%, 79.7%, and 15.9% of the FVPTC, respectively. These immunohistochemical features of FVPTC were between those of classic papillary thyroid carcinoma (CPTC) and those of non-PTC. The CD56 expression was positive in 75.4% of the FVPTC, which is much higher than that of the CPTC (28.3%), and even higher than that of the non-PTC lesions (60%). Comparing FVPTC with CPTC, the expression of galectin-3 was significantly higher and the expression of CD56 was significantly lower in the CPTCs. Comparing the FVPTC with follicular carcinoma (FC), the expression of all the markers was significantly higher in the FVPTC. Comparing PTC with FC, the expression of CD56 was lower and the expressions of the other markers were higher in the PTCs. CONCLUSIONS: Galectin-3, HBME-1, and p63 can help make the diagnosis of FVPTC, and a cocktail of these markers can be even more useful. But CD56 is not thought to be useful to make the diagnosis of FVPTC.

Evaluation of Low-Grade Squamous Intraepithelial Lesions, Cannot Exclude High-Grade Squamous Intraepithelial Lesions on Cervical Smear

BACKGROUND: We examined cervicovaginal smears that contained definite low-grade squamous intraepithelial lesion (LSIL) cells and rare atypical cells suggestive of high-grade SIL (HSIL) (ASC-H) or contained borderline dysplastic cells between LSIL and HSIL. Such lesions were classified as LSIL-H. This study aimed to investigate the cytologic and histologic characteristics of LSIL-H category and we evaluated the associated clinical risk. METHODS: The histologic outcomes of LSIL-H were compared with those of LSIL and ASC-H. Both the cytologic and histologic findings of LSIL-H that were confirmed as cervical intraepithelial neoplasia 2 (CIN2) or greater (CIN2+) were investigated. RESULTS: LSIL-H accounted for 0.09% of the Pap tests. On the follow-up histology, the most frequent outcome was CIN2, and the risk of CIN2+ was higher than that for ASC-H. In the cases of LSIL-H that was histologically confirmed as CIN2+, most of the atypical cells suggestive of HSIL were cytologically similar to those of CIN2, and the corresponding cervical tissues were characterized by small CIN2+ lesions in a large background of flat condyloma/CIN1. The LSIL-H cases not confirmed on initial colposcopically-directed biopsy required further follow-up. CONCLUSIONS: LSIL-H may be a valid diagnostic category with distinctive features that are different from LSIL or ASC-H. LSIL-H needs further follow-up for the proper management.

Evaluation of Low-Grade Squamous Intraepithelial Lesions, Cannot Exclude High-Grade Squamous Intraepithelial Lesions on Cervical Smear

BACKGROUND: We examined cervicovaginal smears that contained definite low-grade squamous intraepithelial lesion (LSIL) cells and rare atypical cells suggestive of high-grade SIL (HSIL) (ASC-H) or contained borderline dysplastic cells between LSIL and HSIL. Such lesions were classified as LSIL-H. This study aimed to investigate the cytologic and histologic characteristics of LSIL-H category and we evaluated the associated clinical risk. METHODS: The histologic outcomes of LSIL-H were compared with those of LSIL and ASC-H. Both the cytologic and histologic findings of LSIL-H that were confirmed as cervical intraepithelial neoplasia 2 (CIN2) or greater (CIN2+) were investigated. RESULTS: LSIL-H accounted for 0.09% of the Pap tests. On the follow-up histology, the most frequent outcome was CIN2, and the risk of CIN2+ was higher than that for ASC-H. In the cases of LSIL-H that was histologically confirmed as CIN2+, most of the atypical cells suggestive of HSIL were cytologically similar to those of CIN2, and the corresponding cervical tissues were characterized by small CIN2+ lesions in a large background of flat condyloma/CIN1. The LSIL-H cases not confirmed on initial colposcopically-directed biopsy required further follow-up. CONCLUSIONS: LSIL-H may be a valid diagnostic category with distinctive features that are different from LSIL or ASC-H. LSIL-H needs further follow-up for the proper management.

Absence of the Septum Pellucidum Associated with a Midline Fornical Nodule and Ventriculomegaly: A Report of Two Cases

We report two autopsy cases that revealed the partial absence of the septum pellucidum with ventriculomegaly. In each case, the brain showed mild dilatation of both frontal horns of the lateral ventricles, normal third and fourth ventricles and no aqueductal stenosis. The posterior portion of the septum pellucidum was absent and the fornices were fused in a single midline nodule, abnormally displaced to a caudal position and lodged in the foramina of Monro. The brain base showed no apparent abnormalities; the optic nerves were well developed. We conclude that the caudally displaced fornix in the absence of the septum pellucidum may have intermittently obstructed the foramina of Monro and induced mild ventriculomegaly.

Adenomatoid tumors of female genital tracts: An analysis of 195 cases / 대한산부인과학회지

OBJECTIVE: Adenomatoid tumors of female genital tracts are benign lesions derived from mesothelium, occurring most commonly during the reproductive years. The aim of this study was to evaluate the overall incidence of adenomatoid tumors in Korean women and to analyze the clinical characteristics. METHODS: One hundred and ninety five patients with adenomatoid tumors were found in a retrospective medical records review of pathologic reports for 44,984 benign uterine diseases at Cheil General Hospital, from January 1995 to April 2009. RESULTS: The overall incidence rate was 0.42% of all benign uterine disease. Among them, 149 patients received hysterectomy, and 46 patients received uterine conservative surgery. Main symptoms of the patients were pain (25.1%), bleeding (30.2%), and palpable mass (18.5%). Most common associated pathologies were leiomyoma (46.6%), adenomyosis (25.1%) and endometriosis (13.1%). Most of the diagnosis was made postoperatively. Among 46 patients with conservative treatment, 13 patients showed successful pregnancy outcome. No recurrence occurred during the follow up period. CONCLUSION: Adenomatoid tumors are associated with fibroids and tend to mimic them clinically, making pre-operative diagnosis difficult. The recurrence is rare even after conservative operation. Our data about this benign neoplasm may be helpful for counseling patients after operations.

Cytology of Synovial Fluid in Gouty Arthritis: Two Cases Report

Synovial fluid (SF) aspiration cytology is a useful diagnostic tool. For patients with gouty arthritis, the diagnosis is confirmed by the presence of monosodium uric acid (MSU) crystals in the SF, and these crystals are long, pointed ended and needle-shaped and they show strongly negative birefringence. Sometimes, it is difficult to diagnosis between gouty arthritis and other type of inflammatory arthritis. We experienced two unusual cases of gouty arthritis that we performed SF analysis for. The first patient was a 35 year old male who presented with relatively typical clinical symptoms with hyperuricemia, but the SF showed acute inflammatory cells without crystals on light microscopy. Only a few suspected crystals of MSU were identified on polarizing microscopy. The second patient was a 45 year old male who presented with atypical symptoms and pain and swelling of the left ankle and knee joint for 3 weeks. The uric acid level in the serum and urine was increased, but not over the normal limit. However, on light and polarizing microscopy, there were numerous MSU crystals in the SF. Conclusively, in some cases of gouty arthritis, the crystals are not identified on light microscopy or the uric acid level is not dramatically increased. So, the polarizing microscopy, the clinical information and the laboratory findings are all included in the work-up when evaluating the SF cytology of arthritis patients.

Histologic Correlation of Atypical Glandular Cells in Cervical Smears

BACKGROUND: The study evaluated the histologic correlation and clinical significance of atypical glandular cells (AGC) detected either on conventional smears (CS) or liquid-based cytology (LBC). METHODS: Two hundred and seventy-seven (0.11%) of 261,925 cervical smears were interpreted as AGC by the Bethesda system 2001 from January 2006 to December 2008. Cytohistological correlation was performed on 192 cases. RESULTS: The prevalence of AGC was 0.07% and 0.13% for CS and LBC smears, respectively. Distribution of AGC subcategories were as follows: atypical endometrial cells 53.8%, atypical endocervical cells 22.7%, atypical glandular cells 19.5%, atypical endocervical cells favoring neoplasia 2.2%, and atypical glandular cells favoring neoplasia 1.8%. Fifty-nine (27.4%) of 192 patients were confirmed as having clinically significant lesions comprising endometrial adenocarcinoma (12.5%), endometrial hyperplasia (6.0%), cervical adenocarcinoma (2.3%), high-grade squamous intraepithelial lesion (HSIL) (1.9%), low-grade SIL (1.9%), adenocarcinoma in situ (1.4%), or ovarian metastasis (1.4%). Conclusion: Compared with CS, LBC was presently associated with a higher prevalence of AGC. Histologic follow-up showed a very low HSIL rate compared to other studies. Endometrial adenocarcinoma was the most common malignant lesion detected because of increasing prevalence of endometrial adenocarcinoma, concentration on endometrial cytology, and introduction of LBC.

Cytologic Findings of Malakoplakia of the Uterine Cervix and the Vagina: A Case Report / 대한세포병리학회지

Malakoplakia is an uncommon chronic granulomatous inflammation that usually involves the urinary and gastrointestinal tracts, but rarely affects the female genital tract. We experienced a case of malakoplakia in a cervicovaginal smear in a 54-year-old woman. Colposcopic examination showed a friable, easily bleeding tissue in the uterine cervix and the vaginal fornix. The cervicovaginal smear consisted of numerous isolated histiocytes, polymorphonuclear leukocytes, lymphocytes, and plasma cells. The histiocytes had an abundant, granular, and degenerated cytoplasm with inflammatory cell debris. Michaelis-Gutmann bodies were readily identified.

The Effect of Tumor Characteristics on the Repeated Nondiagnostic Fine-needle Aspiration Biopsy Results in Thyroid Nodules / 대한내분비외과학회지

PURPOSE: The management of nondiagnostic fine-needle as-piration biopsy (FNAB) of thyroid nodules has not been determined because the significance of persistent nondiagnostic FNAB has been underestimated. The purposes of the present study were to estimate the likelihood of malignancy in patients with nondiagnostic FNAB results and to evaluate whether tumor factors could affect the nondiagnostic FNAB results. METHODS: 2,400 FNABs were performed for thyroid nodules at our institution from 2001 to 2005. A total 294 patients who had initial nondiagnostic results were the subjects of this study. We retrospectively reviewed the age, gender, tumor size, the sonographic findings, the FNAB results and the pathologic reports. RESULTS: The initial nondiagnostic rate was 12.3% (294/2,400). Among the 294 initial nondiagnosted patients, FNAB was secondarily performed in only 99 patients. Seventy patients (70.7%) were diagnostic and 29 (29.3%) remained nondiagnosed. Twenty of seventy diagnosed patients had malignant FNAB results, including atypical cells, and the other 50 patients were benign. The causes of nondiagnostic FNAB results by pathologic descriptions were 43.1%: scanty cellularity, 29.2%: blood, 13.2%: fluid or colloid, 11.1%: inconclusive, and 3.5%: dry artifact. There are no differences in the nondiagnostic rate according to tumor size (P=0.2) and calcification (P=0.7). When the sonographic results could predict the pathologic results, no difference was noted according to the sonographic findings that determined malignancy (P=0.4). Ten percent of the initial nondiagnostic FNAB results were finally reported as malignancy. CONCLUSION: Scanty cellularity and blood aspiration were the major causes of nondiagnostic FNAB results (43.1% and 29.2%, respectively). Tumor characteristics such as tumor size, the presence of calcification and sonographic findings did not predict nondiagnostic FNAB results. Reaspiration biopsy for the initially nondiagnostic FNAB in the thyroid nodules had a high probability of achieving a nondiagnositc result. Because nondiagnostic FNAB of the thyroid nodules may be associated with a relatively high probability of thyroid malignancy, a nondiagnostic FNAB should not be considered as benign. So, if reaspiration biopsy is nondiagnostic, it should be the subject of concern or the patient might be considered for surgery with taking into account the other characteristics, in particularily malignant sonographic findings.

Heterogeneity of Invasive Ductal Carcinoma: Proposal for a Hypothetical Classification

To investigate what heterogeneity exists in breast cancer, 228 consecutive patients with operable invasive duetal carcinoma (IDC), not otherwise specified, were categorized on the basis of the horizontal progression model of carcinogenesis. Using the reversed Black's nuclear grade (RBNG) in the IDC component and the association of ductal carcinoma in situ (DCIS), the patients were classified into pure IDC (IDC de novo or ab initio) as Group I, non-high grade (RBNG 1 and 2) IDC with DCIS as Group II, and high grade (RBNG 3) IDC with DCIS as Group III. The Groups classified in the present study appeared as a prognostic factor independent of known prognostic and predictive factors in multivariate test. Group I had the worst prognosis among the three groups and was the most non-responsive to tamoxifen. After performing stratifying analyses by group, it was found that metastasis-free survival was statistically associated with the status of hormone receptors estrogen receptor and progesterone receptor and tamoxifen therapy only in Group II. In addition, the status of c-erbB-2 expression had prognostic significance only within the Group III. Our results may be used to frame an alternative hypothetical model for breast cancer evolution and will lead us to reconsider the tailoring of the comprehensive therapeutic modality used at the present time.

MET Expression in Sporadic Renal Cell Carcinomas

Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC, all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis. On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative or focally positive for MET expression. In clear cell RCC, MET expression was positively correlated with high nuclear grade, presence of infiltrative growth, tumoral necrosis, papillary architecture, sarcomatoid component, tumoral involvement of the renal pelvis or ureter, involvement of the calyx, and lymphatic invasion. In conclusion, diffuse and strong expression of MET in papillary RCC and collecting duct carcinoma might be helpful in discriminating from the other subtypes of RCC with tubular or papillary growth. In case of MET expression observed in clear cell RCC, it might correlate with those clinicopathological parameters implying aggressive behavior.

Telomerase activity and Expression of MIB-1, Fas and Fas Ligand in Placentas from Women with and without Intrauterine Growth Retardation

BACKGROUND: The placenta from a pregnancy that is complicated by intrauterine growth retardation (IUGR) tends to be smaller than that from a normal pregnancy. To investigate this difference, we analyzed the telomerase activity, the proliferative activity and the mRNA levels of apoptosis mediators in placentas. METHODS: In 20 placentas from normal third-trimester pregnancies and 22 placentas form pregnancies that were complicated by IUGR, the telomerase activity was detected by a telomeric repeat amplification protocol assay. The proliferative activity was assessed by immunohistochemical staining using the MIB-1 monoclonal antibody. The expression of the apoptosis mediator was evaluated by semi-quantitative reverse transcription-polymerase chain reactions for fas and fas ligand. RESULTS: Telomerase activity was detected in 2 (10%) of 20 normal placentas, whereas it was not observed in all tested 13 placentas that were associated with IUGR. The proliferative activity was significantly low in the placentas that were associated with IUGR (7.44+/-2.96%), compared with the normal placentas (11.0+/-3.48%, p=0.002). There was no statistically significant difference in the mRNA levels of fas or fas ligand between two groups. CONCLUSIONS: Low telomerase and proliferative activities in the placenta may play a role in the pathogenesis of IUGR.

Cytologic Findings of Cervicovaginal Smears in Women with Uterine Papillary Serous Carcinoma

The goal of this study was to evaluate the cytomorphologic features of histologically confirmed uterine papillary serous carcinomas (UPSC) of the endometrium. We reviewed cervicovaginal smears from 12 patients with UPSC who had done their cervical smears at six months to a year earlier before the time of diagnosis; nine smears (75%) were diagnosed as positive for malignancy and three smears (25%) were diagnosed as negative. The cervical smears of patients with UPSC revealed frequent papillary clusters that were composed of large pleomorphic tumor cells with prominent nucleoli in a background of necrosis. Other findings revealed from the tests were relatively frequent single malignant cells and bare nuclei. Although the Pap smear is not a sensitive screening test for endometrial carcinoma, we could depend on it to reveal the cytologic features of UPSC which are fairly characteristic and reliable for a preoperative diagnosis of UPSC. Preoperative identification of this poor prognostic variant of endometrial carcinoma may influence the surgical management of these cases and the choice of adjuvant therapy.

Prognostic Role of HER-2 according to Lymph Node Involvement in Invasive Ductal Carcinoma of Breast

PURPOSE: This study was conducted to investigate the prognostic value of HER2 in breast cancer patients. METHODS: A total of 100 consecutive formalin-fixed, paraffin- embedded sections of invasive ductal carcinomas were evaluated by immunohistochemical staining (IHC) and a fluorescence in situ hybridization (FISH) assay for HER2. The cases of 0/1+ IHC were regarded as negative and 3+ as positive. Among the 100 cases tested by IHC, the 2+ cases were confirmed by FISH. RESULTS: Twenty-seven of 100 cases (27%) were confirmed positive for HER-2, which was significantly correlated with the nuclear grade (NG), ER and PR (P=0.014, P=0.004, and P=0.023, respectively). The mean disease-free survival periods (DFS) and overall survival periods (OS) of the HER-2-positive and -negative patients were 64.6+/-6 months and 82+/-3 months (P=0.0031), and 70+/-6 months and 85+/-2 months, respectively (P=0.0096). Of the 48 axillary lymph node (LN) positive patients, the mean DFS and OS of the HER-2-positive and -negative patients were 46+/-9 months and 80+/-4 months (P=0.0007) and 54+/-9 months and 83+/-4 months, respectively (P= 0.001). In the LN negative patients; however, HER-2 overexpression showed no significant correlation with the prognosis. In a multivariate analysis, DFS was significantly correlated with LN involvement and HER-2 overexpression (P=0.015, and P=0.0396, respectively). However, with regard to the OS. LN involvement and NG were statistically significant (P=0.041, and P=0.0125, respectively). CONCLUSION: This study indicates that HER-2 overexpression may play a useful role as an indicator of poor prognosis in invasive ductal carcinoma of breast, especially in LN positive patients.