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Author: search.filters.author.Ivkovski, LjubeSubject: search.filters.subject.estrogen receptor

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    Predictive value of estrogen receptors evaluated by immunocytochemical analysis in breast cancer patients
    (Gustav Fischer, 1997-09)
    Yashar, Genghis
    ;
    Ivkovski, Ljube
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    ;
    Zografski, George
    BACKGROUND: 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.
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    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
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    ;
    Ivkovski, Ljube
    ;
    Zografski, George
    Introduction: 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.
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    Association between Her2/neu expression and hormon receptor status in breast cancer patients.
    (2002-06)
    Yashar, Genghis
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    ;
    Kraleva, Slavica
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    Vasev, Nikola
    ;
    Ivkovski, Ljube
    Determination 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.
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    Preoperative determination of DNA ploidy and hormone receptor status (ER and PgR) on cytologic material from breast cancer patients using image cytometry
    (Karger, 1997-09)
    Ivkovski, Ljube
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    ;
    Zografski, George
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    Yashar, Genghis
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    Stavrik, George
    OBJECTIVE: FNAB of breast masses is a commonly performed diagnostic test. DNA ploidy, along with estrogen (ER) and progesterone (PgR) receptors, is becoming increasingly useful as a prognostic adjunct to conventional staging and histologic grading. These prognostic parameters could be assessed preoperatively by using FNAB material. STUDY DESIGN: Sixty-three breast cancer aspirates were assayed for DNA distribution patterns and hormone receptor status with the CAS 200 Image Analyzing System. Consequently, their relations with well-established conventional prognostic factors in breast carcinoma (tumor size, lymph node status and histological grade) were analyzed. RESULTS:The majority of the primary invasive breast carcinomas were aneuploid (43/63). Most of the aneuploid tumors had histogram type IV (31/43). The data showed that breast carcinomas in which the DNA amounts of the tumor cells were euploid (histograms of types I and I1) were characterized by high levels of ER and PgR, while aneuploid types (histograms of types III and IV) had low levels of ER and PgR. Of the aneuploid breast carcinomas, 86.1% (37/43) had lymph node involvement, while only 40% (8/20) of the euploid carcinomas had lymph node involvement. The majority of the aneuploid carcinomas were of ductal type (29/43), while most of the lobular carcinomas were euploid (9/20). CONCLUSION: Our results strongly indicate a correlation between nuclear DNA distribution patterns, hormone receptor levels and postsurgical factors of prognosis in primary breast carcinomas. By determining the DNA ploidy and hormone receptor status preoperatively, the planning of treatment options available to breast cancer patients could be improved.