Faculty of Medicine
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Item type:Publication, Predictive value of estrogen receptors evaluated by immunocytochemical analysis in breast cancer patients(Gustav Fischer, 1997-09) ;Yashar, Genghis ;Ivkovski, Ljube; Zografski, GeorgeBACKGROUND: The determination of estrogen receptor (ER)status is valuable in selecting the appropriate therapy and predicting prognosis for patients with invasive breast carcinoma. OBJECTIVE: The aim of our study was to assess the predictive value of ER status evaluated preoperatively by immunocytochemical analysis and compared with recurrence rate, clinical and histopathological features in 52 patients with breast carcinoma. MATERIALS AND METHODS: Fifty-two aspirates obtained by fine-needle-aspiration biopsy (FNAB) were prepared as cytospin samples for ER-immunocytochemical analysis (ER-1CA). Cytospin slides were stained using a standard procedure with horseradish peroxidase-antiperoxidase (PAP) method, utilising monoclonal antibody to ER (H222SP, ER-ICA kit, Abbott Laboratories, USA). The assessment of staining was scored in a semiquantitative fashion incorporating the intensity and the distribution of stained cells and the values were designated as IS-CYTOSCORE. All the patients underwent radical mastectomy with axillar lymphadenectomy during the period from September 1990 to March 1992 and were staged according to the postoperative pTNM classification of UICC (1987) guidelines. During the follow-up period (range, 2-75 months, mean 32) recurrences were observed in 25 (48%) patients.ER status was correlated to recurrence rate, age of the patients, type of the breast carcinoma, tumor size, grade of histologic differentiation, desmoplastic reaction, elastosis, necrosis and calcifications. The comparison was made by cross-classification and statistical significance determined by χ2 and Fisher's exact test. RESULTS: ER status was positively detected in 28 (53.8%) patients. There is significant association between ER status and age of the patients (p = 0.02), the type of the breast carcinoma (p = 0.018), and the recurrence rate (p = 0.012). Eighteen out of 26 (70%) patients 50 years or older, were positively related to ER status. In 22 (42.3%) lobular carcinomas, ER status was positive in 16 (73%) patients, compared with 30 (57.7%) ductal carcinomas, with ER status positive for 12 (40%) patients, only. Recurrences were observed in 16 (64%) patients with ER- breast carcinomas and 9 (36%) patients with ER+ breast carcinomas. Less important histopathological features as elastosis and calcifications, demonstrated statistically significant positive relation with ER status (p = 0.004 and p = 0.005, respectively). No significant association was found between the ER status and other histopathological characteristics. CONCLUSION: Our results suggest that recurrences, age of the patients and the lobular type of breast carcinoma are positively correlated with ER status. These data are consistent with the results of other similar studies. On the other hand, the stage of the disease as well as the grade of histologic differentiation and lymph node involvement, demonstrated no significant association with ER status as expected. A small number of cases studied and the heterogeneous stages included, could explain some of the differences between our data and the results from other studies. Semiquantitative ER-1CA, as fast and simple method, is especially useful in determination of ER status in recurrent, metastatic and small-sized breast carcinomas. The great advantage of ER-ICA is in a possibility of ER status preoperative determination, and repeating the procedure, if necessary. Despite the good performances, some inherent difficulties must be noted: subjectivity in scoring and detection by antigenicity of ER. Therefore, ER status quantitative assessment by using Cell-Analysing-System (CAS) and concomitant quantitative measurements of progesterone receptor status, should be of additional benefit. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Postoperative TNM classification of breast cancer. Implications for further treatment (1989-1995)(University of Niš Faculty of Medicine and the Department of the Serbian Medical Society Niš, 1996-06) ;Yashar, GenghisThis study includes 1403 postoperative breast cancer specimens elaborated in our laboratory over the period of last 7 years. The average age of the patients is 54.36 years (range 22-90) and the majority are in the age groups of 41-50 and 51-60 (55.95%). The size of the primary tumour (longest diameter) belongs mostly to the category of T2 (primary tumor 2-5 cm). There are 831 cases in this group or 59.23%. Metastatic spread in the regional lymph nodes is absent in 541 cases (38.56%) and in 278 cases (19.81 %) metastatic deposits are encountered in N1biv category (bigger than 2 cm, in the greatest diameter). The most common type of breast cancer is ductal carcinoma which is present in 649 cases (46.26%). Grade of histologic differentiation is mostly moderate (G2) with 864 cases (61.58%). The majority of the patients are in the stage II of the disease (IIA +IIB = 953 cases or 67.97%). In comparision to the similar studies found in the available references it is obvious we have fewer patients in the stage I but the same number in stage II where the disease is more advanced. This means that examination and diagnosis of the breast cancer is for a step later than the degree when usually more agressive therapy is needed considering the percent of the patients in the higher stages of the disease. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Axillary lymph node metastases in early (pT1) breast carcinomas: Most of the common prognostic factors lack predictive value.(University of Ioannina, 2003-09) ;Yashar, Genghis; ;Ivkovski, LjubeZografski, GeorgeIntroduction: Axillary lymph node status is an important prognostic feature for patients with breast cancer, but the diagnostic and therapeutic value of axillary lymph node dissection in early breast carcinomas has been questioned. Aim: The purpose of this retrospective study was to determine whether routine biological tumor markers, in addition to conventional clinical and histopathological features can predict axillary lymph node metastases in early breast carcinomas (pT1). Material and methods: Data from 90 patients with pT1 breast cancer who underwent radical mastectomy or lumpectomy with axillary lymph node dissection between January 2000 and April 2003 were investigated. The association between axillary lymph node status and several clinicopathological factors (age, size, tumor grade, histological type), as well as immunohistochemical expression of estrogen and progesterone receptors (ER/PgR), Ki-67 and p53, were analyzed. Hormone receptor status, Ki-67 and p53 expression were assessed by immunohistochemistry and the results were evaluated by performing the standardized scoring system. Results: From the total of 90 patients, 35 (396) were with axillary lymph node metastases. Among the factors studied only the tumor size appeared to correlate with the incidence of lymph node involvement, but this was not statistically significant (p=0.07). Axillary lymph node involvement was present in 4 (286) of the 19 patients with primary tumors <1cm (pT1a+pT1b), compared with 31 (44%) of the 71 with tumors >1cm (pT1c). Hormone receptor status, proliferative activity (Ki-67), and p53 expression were not predictors of nodal involvement in early breast carcinomas. Conclusion: Therefore, biological tumor markers as well as most of the common prognostic clinicopathological factors are not reliable predictors of lymph node metastasis in early breast carcinomas. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, HER2/neu expression in correlation with p53 and Ki-67 immunoreactivity and clinicopathological parameters in breast cancer patients.(Blackwell Publishing, 2002-10) ;Yashar, Genghis; ;Ivkovski, Ljube ;Kraleva, SlavicaProdanova, IrinaIntroduction: Although the role of HER2/neu status is still unsettled, its determination is valuable in selecting breast carcinoma patients for adequate Herceptin therapy. Aims: The purpose of this study was to evaluate the association among HER2/neu, p53 and Ki-67 immunoreactivity, as well as clinicopathological parameters (tumour size, histopathologic grade, nuclear grade, tumour type. lymph-node status and age) in breast cancer patients. Materials and methods: HER2/neu, p53 and Ki-67 expression was determined in 169 post-operative stage I-III (UICC. 1997) breast cancer patients using the standardized DAKO HercepsTest and by immunoperoxidase technique. respectively. The results were evaluated by performing the standardized scoring system. Discussion and conclusion: HER2/neu expression was positive in 66 patients (37%). There was no association between HER2/neu expression and p53 or Ki-67 immunoreactivity as well as any clinicopathological parameter, while the values of Ki-67 and p53 were strongly interrelated (P < 0.001). Ki-67 was also in significant correlation to tumour size, lymph-node involvement and tumour type (P<0.001), while p53 was only related to patients' age (P <0.01). These results indicate that HER2/neu is an independent prognostic marker in differentiating a subgroup of high-risk breast cancer patients. Additional studies are required to adjust HER2/neu testing results to clinical outcome. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Association between Her2/neu expression and hormon receptor status in breast cancer patients.(2002-06) ;Yashar, Genghis; ;Kraleva, Slavica ;Vasev, NikolaIvkovski, LjubeDetermination of HER2/neu expression by immunohistochemistry is mandatory for application of Herceptin® therapy in breast cancer patients. The purpose of this study was to investigate the association between HER2/neu expression and hormone receptor status, as well as with other clinicopathological parameters in breast cancer patients. HER2/neu, p53 and Ki-67 expression was determined in 169 postoperative stage I-III (UICC, 1997) breast cancer patients using the standardized DAKO HercepsTest® and immunoperoxidase technique, respectively. The results of HER2/neu immunoreactivity were evaluated by performing the standardized scoring system (0 = negative, 1+ = weakly positive, 2+ = positive, 3+ = strongly positive staining), while ER and PgR were scored in a semiquantitative fashion (ER-ICA and PR-ICA). The results from HER2/neu expression were correlated to hormonal receptor status and clinicopathological parameters (tumor size, histopathologic grade, nuclear grade, histologic type of the tumor, lymph node status and patient age). Statistical significance was determined with χ2 and Fisher’s exact test. HER2/neu expression was positive in 66 patients (37%). There was no significant association between the values of HER2/neu and ER/PgR status, or with any other clinicopathological parameter. ER status significantly correlated with PgR status (p<0.01), tumor size (p<0.01), lymph-node involvement (p<0.01) and tumor type (p<0.01). PgR status was related to the histopathologic grade (p<0.01), lymph-node status (p<0.01), tumor type (p<0.01) and patient age (p<0.01). HER2/neu is a relatively new promising marker in predicting the response to target specific therapy. However, its predictive value remains a complex and inconclusive subject. According to our results, the prognostic potential of HER2/neu seems to be independent from hormone receptor status and any other clinicopathological parameter in breast cancer patients. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Impact of size of the tumour, persistence of estrogen receptors, progesterone receptors, HER-2 neu receptors and Ki67 values on positivity of sentinel lymph node, in patients with early breast cancer(2018-05-18)In surgical treatment of breast carcinoma axillary lymphadenectomy has diagnostic role (clinical staging), and therapeutic role (removing cancerous lymph nodes, which is less important due to the systemic treatment with medications). The introduction of “sentinel lymph node biopsy”, is possible due to analyze of one or few lymph nodes, to determines the lymph node status of all others lymph nodes and enables a minimally invasive treatment approach. Determining the criteria (primary tumor size, presence of estrogen and progesterone receptors, Ki67 index value and HER-2 status) that impacts positivity in the “sentinel lymph node” or in other nodes in the axilla will enable the application of the “sentinel lymph node biopsy” technique only in cases when it is really necessary, without exposing the patient to residual disease in the axillary lymph nodes. Aims: 1. Introducing the method for “sentinel lymph node detection and biopsy” in daily clinical practice. 2. Examining the impact of tumor size, presence of estrogen receptors, progesterone receptors in tumor cells, Ki67 index value and HER-2 positive status, positivity of the “sentinel lymph node” in the axilla in patients with early breast cancer. 3. Examining the impact of tumor size, presence of estrogen receptors, progesterone receptors in tumor cells, Ki67 index value and HER-2 positive status, positivity of the “non-sentinel lymph node” in the axilla in patients with early breast cancer with positive “sentinel lymph node”. Materials and methods: A prospective study was conducted on 80 patients with early breast cancer (T1,2 N0 M0) in which the “sentinel lymph node” were detected with preoperative application of radio-collide and Methylene blue dye 0.005%. After the biopsy of these lymph nodes the breast were radically operated, followed by histopathological analysis of the “sentinel lymph node” and primary breast cancer histopathology. In patients with metastatic disease in the “sentinel lymph node” ( on frozen section or paraffin section), a complete lymphadenectomy were performed on the other lymph nodes in the axilla. Breast carcinoma of all patients undergone a routine examination with immunohistochemical analysis for the presence of estrogen receptors, progesterone receptors, Ki67 and HER-2. A total of 81 patients with same disease characteristics were examined in the control group, and patients undergone radical surgery of the breast with complete axillary lymphadenectomy. All data was added to the Excel database, and the statistical analysis was completed in statistical software Statistics 10. Results: After having analyzed the results we can conclude that we tested two homogenous and comparable groups. There is no statistically significant difference between the basic parameters of these groups, therefore the groups are comparable. Naturally, some of the parameters are different (complete lymphadenectomy was performed in the control group) therefore there is a different number of lymph nodes removed. During the research we found the statistically significant predictive role of Ki67 2 + (p=0.012), progesterone receptors (+) of tumor cells (p=0.045) on the positivity of the “sentinel lymph node”. During the research we found the statistically significant predictive role of tumor size (p=0.024) and Кi67 3+ (p=0.013), impacts the positivity of the “non sentinel lymph node”. With multiple regression analysis we found that tumor size is statistically significant criteria for the positivity of lymph nodes in the axilla in control group patients (p=0.014). There were no intraoperative complications in any of the two groups. Early complications were significantly more frequent in the control group and we found significantly different results regarding the presence of seroma (Hi2=68,3 p=0,001), pain in the axilla (Hi2=28,8 p=0,001), sensory deficit (Hi2=102,1 p=0,001), shoulder pain, swelling of the hands and the arms. Some of these are prolonged complications therefore there are significant differences between the control group and the test group regarding pain in the axilla (Hi2=8,3 p=0,001), sensory deficit (Hi2=69,6 p=0,001) and shoulder pain (Hi2=45,8 p=0,001). In reality, there is even a greater difference knowing that patients in the test group underwent “sentinel lymph node detection and biopsy” and if metastatic deposit is found in the lymph node (which is the case with 30% of the patients) a complete axillary lymphadenectomy is performed. This is the most significant outcome of this study.
