The effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes in patients with breast cancer.

Aim: This study investigated the effect of neoadjuvant chemotherapy (NAC) on stromal tumor-infiltrating lymphocytes (sTILs) and their treatment response. Materials & methods: 115 patients with pre-NAC core biopsies and post-NAC surgical resection specimens were reviewed. Results: There was no significant change between pre- and post-treatment sTILs. Both pre- and post-NAC sTILs were significantly lower in patients with luminal A subtype. An increase in sTILs was observed in 21 (25.9%) patients after NAC, a decrease in 29 (35.8%) and no change in 31 (38.3%; p = 0.07). Pretreatment sTIL density was independent predictor of pathological complete response in multivariate analyses (odds ratio: 1.025, 95% CI: 1.003-1.047; p = 0.023). Conclusion: High sTIL density in core biopsies was independently related to pathological complete response. In addition, ER appears to be the most crucial factor determining the rate of sTIL.

New studies have shown that the tumor microenvironment is critical in tumor behavior. Immune cells surrounding tumor cells are the main components of the tumor microenvironment. Our study aimed to investigate the change in immune cells before and after chemotherapy in breast cancer patients. Our study included 115 patients. All patients underwent chemotherapy before surgery to shrink the tumor. Tru-cut biopsy pieces and the breast tissue obtained after surgery were examined. The presence of estrogen or progesterone receptors on tumor cells decreased the number of immune cells surrounding the tumor cells. The number of immune cells did not decrease after chemotherapy. Another finding was that the greater the number of immune cells around the tumor, the more likely that the tumor would disappear after chemotherapy.

Immunohistochemical HER2 Status Evaluation in Breast Cancer Pathology Samples: A Multicenter, Parallel-Design Concordance Study.

OBJECTIVE: As patients with increased human epidermal growth factor receptor (HER2) overexpression are more likely to benefit from trastuzumab treatment, the accuracy of HER2 receptor status in breast cancer patients is significant for appropriate disease management. However, this assessment is not harmonized and results may be highly variable between centers. The aim of this study was to investigate the degree of interlaboratory variability in the results of HER2 expression reported by 5 participating centers and to assess the concordance between these centers and a reference laboratory.Materials and Methods: A total of 30 breast cancer samples were tested and scored for HER2 expression using immunohistochemical method in 5 centers from Turkey and in a reference laboratory from Netherlands (Academic Medical Center, Amsterdam). All the participating centers had an experience of more than 10 years regarding the HER2 testing. The results were compared both among the centers and with the reference laboratory. RESULTS: When the concordance of participating centers and the reference laboratory was evaluated regarding negative (0-1+), equivocal 2(+) and positive 3(+) classification of HER2 immunostaining, the highest concordance was found in Center-A, and the lowest in Center-C (Kendall's tau-b concordance coefficient 0.911 and 0.724, respectively). The concordance of the centers with reference laboratory was 80.0% both in equivocal and positive samples, while it increased up to 91.8% in negative samples. CONCLUSIONS: This study showed that in general there is sufficiently good agreement between the reference laboratory and the participating centers for immunohistochemical HER2 assessment.

Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long-term survival analysis.

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl-2 regarding prognosis. Sixty-nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow-up data, were collected to analyze ARID1A and bcl-2 expressions immunohistochemically with prognosis. The median follow-up period was 94 months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor-2 (Her-2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4-26.6, P=.02; HR=15.9, 95% CI 3.5-71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1-14.9, P=.04; HR=7.2, 95% CI 2-25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10 year-OS (P=.001) and 10 year-DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her-2 positivity have significant adverse effect clinical outcomes of IMPC patients.

High expression of SALL4 and fascin, and loss of E-cadherin expression in undifferentiated/dedifferentiated carcinomas of the endometrium: An immunohistochemical and clinicopathologic study.

Undifferentiated/dedifferentiated endometrial carcinomas (UCE/DCEs) of the endometrium are rare tumors with poor prognosis. There are few clinicopathologic studies with detailed immunohistochemical analysis regarding UCE/DCEs.We evaluated the diagnostic value of a selected tumor stem-cell marker and epithelial-mesenchymal transition (EMT) markers, in addition to previously studied markers in identifying UCE/DCEs from other types of high-grade endometrial carcinomas.Eleven cases of UCE/DCEs with complete clinical follow-up that were diagnosed between 2006 and 2015 were included in the study. For immunohistochemical comparison, 11 clinically matched cases for each type of other high-grade endometrial carcinomas (high-grade endometrioid (F3-EC), serous [SC], and clear cell carcinoma [CCC]) were used as a control group. An immunohistochemical analysis including fascin, SALL4, E-cadherin, and ß-catenin, in addition to epithelial and neuroendocrine markers was performed in each case.The majority of UCE/DCEs displayed diffuse expression of fascin (81.9%) and loss of E-cadherin expression (54.5%). SALL4 expression was detected in 36.3% of the UCE/DCE cases. SALL4 expression was significantly more frequent in UCE/DCEs than all other high-grade carcinomas (P < 0.001). Loss of E-cadherin and fascin expression was significantly more frequent in UCE/DCEs than high-grade endometrioid and clear cell adenocarcinomas (P = 0.012, 0.014 and P = 0.01, 0.003, respectively).We suggest that loss of E-cadherin expression together with fascin and SALL4 immunopositivity in addition to morphologic features have an impact in differential diagnosis of UCE/DCEs from other high-grade endometrial carcinomas.

Receptor discordance rate and its effects on survival in primary and recurrent breast cancer patients.

PURPOSE: The receptor status of breast cancer plays a critical role in clinical practice. During the metastatic process, a change in the biological characteristics of the tumor can be seen. This study aimed to investigate the hormone receptor and HER2 status changes between primary and recurrent breast cancers and their effect on survival. METHODS: Eighty-six breast cancer patients with biopsy- proven local recurrences or distant metastases during the follow-up period were included in the study. Patients with metastatic disease at the time of first diagnosis or with history of previous neoadjuvant chemotherapy were excluded. RESULTS: Forty-three of the 86 patients (50%) had changes in at least one of the estrogen receptor (ER), progesterone receptor (PR), or HER2. ER, PR and HER2 discordance rates were 12.7, 38.3, and 15.1%, respectively, and PR discordance was significantly higher (p=0.000). Among all molecular subtypes, the triple negative breast cancer (TNBC) subtype showed the least change. When the effect of chemotherapy on receptor change was analyzed, PR discordance was significantly higher in the group who received chemotherapy (p=0.029). Analysis of the hormonotherapy effects on receptor discordance revealed results similar to those of chemotherapy. Only the PR discordance was significantly greater in the group that received hormonotherapy (p=0.000). None of the three receptor discordances or loss of any receptor were related to survival. Primary tumor TNBC subtype and disease-free-interval (DFI) shorter than 5 years were found as independent prognostic factors that negatively affected overall survival (OS). CONCLUSION: This study showed that during recurrent disease there was 50% discordance in the expression of ER, PR, and HER2. The receptor showing the greatest discordance and influence from the systemic treatment was PR. A significant relationship between receptor discordance and survival could not be demonstrated in our study.

Clinical and histopathological factors associated with Ki-67 expression in breast cancer patients.

The aim of the present study was to identify the optimal Ki-67 cut-off value in breast cancer (BC) patients, and investigate the association of Ki-67 expression levels with other prognostic factors. Firstly, a retrospective search was performed to identify patients with stage I-III BC (n=462). A range of Ki-67 index values were then assigned to five groups (<10, 10-14, 15-19, 20-24 and ≥25%). The correlation between the Ki-67 index and other prognostic factors [age, tumor type, histological and nuclear grade, tumor size, multifocality, an in situ component, lymphovascular invasion (LVI), estrogen and progesterone receptor (ER/PR) expression, human epidermal growth factor receptor (HER-2) status, axillary involvement and tumor stage] were investigated in each group. The median Ki-67 value was revealed to be 20% (range, 1-95%). A young age (≤40 years old), tumor type, size and grade, LVI, ER/PR negativity and HER-2 positivity were revealed to be associated with the Ki-67 level. Furthermore, Ki-67 was demonstrated to be negatively correlated with ER/PR expression (P<0.001), but positively correlated with tumor size (P<0.001). The multivariate analysis revealed that a Ki-67 value of ≥15% was associated with the largest number of poor prognostic factors (P=0.036). In addition, a Ki-67 value of ≥15% was identified to be statistically significant in association with certain luminal subtypes. The rate of disease-free survival was higher in patients with luminal A subtype BC (P=0.036). Following the correlation analysis for the Ki-67 index and the other prognostic factors, a Ki-67 value of ≥15% was revealed to be the optimal cut-off level for BC patients.

In situ hybridization analysis of invasive breast carcinomas with immunohistochemically negative Her-2 status (a national multicenter study).

OBJECTIVE: The aim of this study was to determine the rate of Her-2 gene amplification in breast cancer cases with a previous negative Her-2 result as determined by immunohistochemistry (score 0 or 1). MATERIAL AND METHOD: 552 cases of invasive breast carcinoma were assessed with the contribution of 9 centers. Previous immunohistochemistry score was either 0 or 1+ in all cases. These cases were re-tested by Her-2 silver in situ hybridization in the central laboratory. Her-2 gene amplification was defined as Her-2/CEP 17 ratio of more than 2.2. Cases with a ratio between 1.8 and 2.0 were defined as equivocal and cases with a ratio of less than 1.8 were defined as negative. RESULTS: Re-testing of the 552 cases with silver in situ hybridization showed a total of 22 cases with Her-2 gene amplification, of which 11 (3.2%) were found to be score 0, and 11 were found to be score 1+ (5.3%) by immunohistochemistry previously. Her-2 gene amplification rate of cases (score 0 and 1+) ranged from 0% to 10.48% among the centers. Polysomy was found in 28 (8.1%) of the score 0 cases and 25 (12.1%) among the score 1+ cases. Five (9.4%) of the cases with polysomy were found to be amplified, and 48 (90.6%) were not. CONCLUSION: The results of the study show that a group of cases (3.98%) with a potential to benefit from anti-Her-2 therapy may be missed with the immunohistochemical method. This indicates the importance of quality assurance, especially in central laboratories with many breast cancer cases in daily practice.

Successful treatment of triple primary tumor.

INTRODUCTION: The occurrence of multiple primary tumors is rare. Only limited number of cases with triple malignancy have been reported. We report here a rare case of a woman presented synchronous triple tumors, in her lung, breast, skin. PRESENTATION OF CASE: A 56-year-old woman presented with invasive ductal carcinoma of breast, non-small cell lung cancer and malignant melanoma. The patient undergone mastectomy and malignant melanoma tumor excision on-site. After operation stereotactic radiotherapy was given to her lung tumor. Six course of chemotherapy was given to her. She is alive with no progression. DISCUSSION: The patient was diagnosed with melanoma and staging by FDG/PET. There is not any study about routine using PET/CT in the melanoma staging. CONCLUSION: This is a very rare synchronous triple tumor case.

Predictive role of midtreatment changes in survivin, GSTP1, and topoisomerase 2α expressions for pathologic complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

INTRODUCTION: The primary aim of this study is to investigate the effect of change in the expression levels of survivin, glutathione-S-transferase P1 (GSTP1), and topoisomerase 2α (TOP2A) on the response to antracyclin-based and taxane-based neoadjuvant chemotherapy. METHODS: This study included 32 locally advanced breast cancer patients. Tumoral expressions of survivin, TOP2A, and GSTP1 in serial biopsy specimens obtained before treatment, after sequential 4 cycles of doxorubicin+cyclophosphomide, and 4 cycles of docetaxel were analyzed by real-time polymerase chain reaction. Survivin expressions were additionally analyzed in serial blood samples. RESULTS: The pathologic complete response (pCR) rate and the overall response rate (clinical complete and partial) were 28% (n=9) and 91% (n=29), respectively. There were no statistically significant correlations between serial TOP2A expression levels and response. There was a nonsignificant trend toward an improved response rate with decreased survivin expression. A significant decrease in the GSTP1 expression level throughout treatment (P=0.014), which was also shown to be significantly correlated with a pCR (P=0.0001), was seen. Downregulation of GSTP1 after 4 cycles of anthracycline-based combination was independently associated with improved progression-free survival (P=0.01). CONCLUSIONS: Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracycline-based and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.

The importance of endometrial nerve fibers and macrophage cell count in the diagnosis of endometriosis.

BACKGROUND: Endometriosis is a disease that is hard to diagnose without the gold standard method, laparoscopy. An easier diagnostic method is needed. OBJECTIVE: The aim of the study is to determine whether the number of macrophage cells in the endometrium and/or the detection of nerve fibers can be used in the diagnosis of endometriosis. MATERIALS AND METHODS: Endometrial sampling was done to 31 patients prior to laparoscopy (L/S) or laparotomy (L/T) at Istanbul University Istanbul School of Medicine Hospital between January 2010 February 2011. Also 34 patients who were retrospectively chosen from their files were added to the study. 5 patients were excluded from the study. Totally, 31 patients were placed in the endometriosis and 29 patients in the control group. Endometrial samples were evaluated immunohistochemically with the markers protein gene product 9.5 (PGP 9.5) and neurofilament (NF) for nerve fibers and CD68 for macrophages. RESULTS: None of the samples were stained with PGP 9.5 and NF. As for CD68+cells, no statistically significant difference was observed between groups (endometriosis: 216.10±104.41; control: 175.93±43.05, p=0.06). RESULTS were also evaluated in the subgroups of menstruel phases and disease stages. Only in the proliferative phase there was a significant increase in the endometriosis group (p=0.03). No significant difference was observed between the stages. CONCLUSION: The detection of nerve fibers in the eutopic endometrium with the markers of PGP 9.5 and NF is not found to be helpful in the diagnosis of endometriosis. Macrophage cells may be helpful in the diagnosis only in the proliferative phase.

Complete response in a patient with granulosa cell tumor treated with a combination of leuprolide and tamoxifen.

BACKGROUND: Adult granulosa cell tumors (GCTs) are frequently hormonally active. Thus, hormonal agents have been evaluated for the treatment of advanced-stage or recurrent disease. CASE REPORT: A 39-year-old patient presented with recurrent GCT. The patient received multiple treatment modalities, including surgery and 2 different chemotherapy regimens (cisplatin- and taxanebased). Abdominal computed tomography following these treatments showed local recurrence with multiple implants. The patient's inhibin B level increased to 187 pg/ml at this time. The patient was treated with leuprolide 11.25 mg every 3 months and tamoxifen 20 mg twice daily. The patient's inhibin B level began to decrease after 1 month and returned to normal after 4 months. The patient has been maintained on this treatment for 2 years and has tolerated the drugs well. CONCLUSION: The combination of leuprolide and tamoxifen had limited side effects in the presented patient and might be a viable treatment option for women with advanced-stage or recurrent adult ovarian GCTs.

[Pathology laboratories staff workload evaluation in Turkey: a survey study]. / Türkiye'de Patoloji Laboratuvarlarinda Personel Is Yükü Degerlendirmesi: Bir Anket Çalismasi

OBJECTIVE: The workload affects the quality of the pathology report. The aim of this study was to investigate the territorial distribution and productivity of pathology laboratories around Turkey and to estimate the staff workload. MATERIAL AND METHOD: A survey questioning the workload was sent to all Ministry of Health and university hospitals. Staff workload was questioned according to the hospital classification and educational activity to evaluate the productivity. Data were entered using SPSS 16.0 statistical software package program and the distribution criteria, t-test and one-way anova were used in the analysis to evaluate the differences between the averages. RESULTS: An average of 2.8 pathologists worked at the pathology laboratories. A total of 5.500 biopsies and 3.750 cytology specimens were received and 20.000 blocks prepared per year. Pathologists evaluated 1.935 biopsies and 1.400 cytology specimens on average and this is equivalent to 2.718 biopsies per year. Gynecology and general surgery department materials constituted 57 percent of all biopsies. Each technician prepared 6.200 blocks, 11.500 slides and 1.000 immunohistochemistry preparations on average. An average of 3.4 paraffin blocks was prepared for each biopsy. The efficiency was low in 17% of teaching hospitals and 77.8% of non-teaching hospitals. In contrast 62.5% of teaching hospitals had work overload. The majority (70.5%) of the respondents mentioned staff shortage. CONCLUSION: There is no pathologist shortage in Turkey and the problem is workload distribution. Pathology residents' overwork would be reduced by using pathology assistants. There is no shortage of technicians or secretaries, but uneven distribution. Pathology staff planning must be tailored taking into account the features of each hospital. Standard planning for all hospitals is not suitable.

A European network for virtual microscopy--design, implementation and evaluation of performance.

Web-based virtual microscopy has enabled new applications within pathology. Here, we introduce and evaluate a network of academic servers, designed to maximize image accessibility to users from all regions of Europe. Whole-slide imaging was utilized to digitize the entire slide set (n = 154) for the slide seminars of the 21st European Congress of Pathology. The virtual slides were mirrored to five academic servers across Europe using a novel propagation method. Functionality was implemented that automatically selects the fastest server connection in order to optimize the slide-viewing speed ( http://www.webmicroscope.net/ECP2007). Results show that during 6 months of monitoring the uptime of the network was 100%. The average viewing speed with the network was 3.1 Mbit/s, as compared to 1.9 Mbit/s using single servers. A good viewing speed (>2Mbit/s) was observed in 32 of 37 countries (86%), compared to 25 of 37 (68%) using single servers. Our study shows that implementing a virtual microscopy network spanning a large geographical area is technically feasible. By utilizing existing academic networks and cost-minimizing image compression, it is also economically feasible.

Malignant ovarian germ cell tumors: a single-institution experience.

OBJECTIVE: To evaluate the clinicopathologic prognostic factors in malignant ovarian germ cell tumors. METHODS: We reviewed the medical records of 70 patients treated from 1990 to 2006 at our center. Clinical data including demographics, stage, surgery, chemotherapy, survival, menses status, and fertility were collected from patients' charts. RESULTS: Median age was 22 years (range, 9-68). The histologic subtypes included 36 dysgerminomas, 11 yolk sac tumors, 3 immature teratomas, 1 embryonal carcinomas, and 19 mixed types. The most striking clinicopathologic finding was a history of concomitant immunosuppressant therapy, which was observed in 2 patients. Two patients had contralateral sex-cord tumors at presentation and follow-up. During a median follow-up period of 4.6 years, 11 patients had recurrence. The median time to recurrence was 8 months (6-28 months). Recurrences appeared in the abdominopelvic cavity in 9 out of 11 patients. Only one could be salvaged with second-line chemotherapy. Cumulative survival rate was 97% and 60% in patients with dysgerminoma and nondysgerminoma, respectively. Nondysgerminoma histology and residual tumor after surgery were unfavorable prognostic factors (P < 0.001 and P = 0.015). Fertility-sparing surgery was as effective as radical surgery among all eligible patients. Of patients with known menstrual status, 96% had regular menses. Of the 8 patients who opted for conception among these patients, 7 delivered healthy infants. CONCLUSIONS: Nondysgerminomas have an aggressive clinical course. New treatment strategies are needed for eradication of abdominopelvic disease at initial diagnosis and recurrent setting. Occurrence of malignant ovarian germ cell tumors may be associated with immunosuppression in some patients. Sex-cord stromal tumors may present with bilateral involvement. It is possible to maintain fertility after fertility-sparing surgery followed by chemotherapy.

Increased lymph node positivity in multifocal and multicentric breast cancer.

BACKGROUND: Multifocal and multicentric (MF/MC) breast cancers have been reported to be associated with increased lymph node metastases. The limited data on this issue prompted us to investigate the pathologic and clinical differences between unifocal and MF/MC breast cancer. STUDY DESIGN: Between 1990 and 2002, 1,322 patients with operable invasive breast cancer underwent a definitive operation at our Breast Clinic. Patients with MF/MC breast cancer (n=147, 11%) were compared with patients with unifocal breast cancer (n=1,175; 89%) in terms of pathologic and clinical characteristics. RESULTS: Patients with MF/MC were found to have a higher frequency of lymph node metastases when the largest diameter was used as a tumor size estimate for MF/MC cancer (unifocal T1 and T2, 35% and 49%, respectively, versus MF/MC T1 and T2, 48% and 67%, respectively; p=0.05 and p=0.003, respectively). When the combined diameter assessment was used, the frequency of lymph node positivity was similarly higher in MF/MC patients versus unifocal patients (unifocal T1 and T2, 35% and 49%, respectively, versus MF/MC T1 and T2, 49% and 61%, respectively; p=0.08 and p=0.046, respectively). At a median followup of 55 months (range 12 to 153 months), 5-year disease-free survival (DFS; unifocal, 88% versus MF/MC, 82%, p=0.14) and overall survival (OS) rates (unifocal, 92% versus MF/MC, 93%, p=0.43) did not show any significant difference between two groups. CONCLUSIONS: Our data suggest that breast tumors with multiple foci have a different biology, with an increased metastatic potential to axillary lymph nodes, regardless of tumor size, that reflects an advanced stage. The clinical relevance of the currently used TNM classification system, which uses the diameter of the largest nodule, is supported by our findings.

Factors affecting the prognosis of breast cancer patients with brain metastases.

The aim of this retrospective analysis was to investigate the factors affecting the prognosis of brain metastases in breast cancer patients to identify subgroups which might benefit from prophylactic treatments in future. Seventy-three early and 13 advanced stage patients with known Erb-2 status were included. In 14% of the early stage patients, the first recurrence site was isolated brain metastasis. None of the anthracycline resistant patients had brain metastases as their first recurrence site. The median interval between diagnosis and brain metastasis was 41.5 months (95% CI, 35.79-47.20) in early stage patients. The median interval between the first extracerebral metastases to the brain metastases was 15.5 months (95% CI, 12.24-18.76) in all patients. High histologic and nuclear grade, large tumor, anthracycline resistance were the factors which significantly affected the early appearance of brain metastases but only advanced age (> or =55 years, P=.035) correlated with isolated brain metastasis. Progression with isolated brain metastases was significantly higher in responsive ErbB-2 positive population (P=.036) and none of other pathological factors was associated with isolated brain metastasis in advanced stage. The median survival after brain metastasis in patients with brain metastasis as first recurrence was longer than the patients with brain metastasis after other organ metastasis (13 months vs 2 months P=.003). The median survival following brain metastases in complete responsive patients was higher than the others (24 months vs 6 months, P=.002). Therefore, response to systemic treatment was more determinative in the development of isolated brain metastases than clinical and pathologic features. ErbB-2 should be emphasized in prophylactic treatment strategies. Prophylactic cranial radiotherapy may be an effective treatment option for metastatic patients with complete responsive disease and with controlled ErbB-2 positive disease.

Comparison of different injection sites of radionuclide for sentinel lymph node detection in breast cancer: single institution experience.

BACKGROUND: There are still ongoing controversies about several aspects of lymphatic mapping and sentinel lymph node biopsy for breast cancer, including injection site of radioisotope and blue dye. This study aims to evaluate the success rate of different radiocolloid injection techniques in the detection of sentinel lymph nodes (SLN) in early breast cancer. STUDY DESIGN: One hundred ninety-two women with early breast cancer were included. For SLN mapping with lymphoscintigraphy (LSG), 5 different injections were used. Group A (36 patients) had 4 peritumoral (PT), group B (n = 36) had 1 subdermal (SD) injection of Tc-99m rhenium sulfide colloid over the tumor quadrant. Group C (59 patients) had 1 PT and 1 SD combined injections. In group D (56 patients), lymphatic mapping was performed with 2 intradermal periareolar (ID-PA) injections. In group E (n = 41), 2 ID-PA and 1 PT combined injections were performed. Early dynamic and delayed images were obtained. A surgical gamma probe was used to explore the SLNs. Surgical specimens were evaluated histopathologically. The SLN identification rate, false negative rate, and comparison of groups were evaluated by statistical methods. RESULTS: The SLN identification rate by LSG in groups A, B, C, D, and E were 72%; 92%, 93.2%, 98%, and 95%, respectively. The highest detection rates for the axilla (98%) and mammary internal (MI) drainage (22%) were obtained with ID-PA injections and a peritumoral injection, respectively. Seventy of 192 patients (36.4%) had positive axillary lymph nodes. The only statistically significant difference was between the PT and SD injection groups in axillary SLN identification rate by LSG (P = 0.016). CONCLUSION: The success rate was superior with intradermal periareolar injection compared with PT and SD injection to visualize the axillary SLN. However, PT deep injection combined with ID-PA injections may be more favorable to demonstrate the primary internal mammary (IM) lymphatic drainage.

HER-2, TOP2A and chromosome 17 alterations in breast cancer.

HER-2 amplification is a biomarker for identifying patients who respond to trastuzumab and has been evaluated as a factor predicting the response to anthracyclines. The relationship between HER-2 and response to anthracycline therapy may also be the result of the close localization of TOP2A on 17q. It has been a matter of debate whether these two genes, HER-2 and TOP2A, behave separately on different amplicons or act together thus making it possible to predict the TOP2A status from the HER-2 status. In this study TOP2A, HER-2 and chromosome 17 aneusomy were investigated by fluorescent in situ hybridization (FISH) in 50 consecutive breast cancer patients. HER-2 amplification was detected in 11 patients (22%) and TOP2A changes were seen in 6 patients (12%); two amplifications and two deletions were observed in HER-2-amplified cases and two deletions in HER-2-nonamplified cases. Three of the TOP2A-deleted cases had polysomy 17. HER-2 copy number was higher than the TOP2A copy number in one patient with co-amplification. Polysomy was observed in 9 cases (18%) and monosomy in 6 cases (12%). Aneusomy was the sole anomaly in 11 patients (22%). We conclude that the TOP2A status cannot be predicted from the HER-2 status and evaluation of the TOP2A status only in patients with HER-2 overexpression may lead to missing cases with TOP2A deletion with possible resistance to therapy. Other factors modulating topo II activity may also affect the response to therapy. Studies evaluating different parameters that can modulate topo II activity and the response to the drugs targeting the enzyme are necessary.

Siegfried Oberndorfer: a tribute to his work and life between Munich, Kiel, Geneva, and Istanbul.

In 1907 Siegfried Oberndorfer published his observations and interpretations on tumorlets ("Geschwulstchen") in the small intestine, which he called carcinoids ("karzinoide Tumoren"). This article pursues the questions why this discovery was so unique and what role it played in the later life of Siegfried Oberndorfer.