Faculty of Medicine

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HER2/neu expression in correlation with p53 and Ki-67 immunoreactivity and clinicopathological parameters in breast cancer patients.
(Blackwell Publishing, 2002-10)
Yashar, Genghis
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Ivkovski, Ljube
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Kraleva, Slavica
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Prodanova, Irina
Introduction: 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.
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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
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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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Her2/neu expression in breast cancer patients - Correlation with estrogen and progesterone receptor status, p53 and Ki-67 immunoreactivity and clinicopathological parameters
(Institute of Oncology, Sremska Kamenica, Yugoslavia, 2002-09)
Yashar, Genghis
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Prodanova, Irina
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Vasev, Nikola
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Kraleva, Slavica
Although the role of HER2/neu status is still unsettled, its determination is valuable in selecting breast carcinoma patients for adequate Herceptin¨ therapy. The purpose of this study was to investigate the association between HER2/neu expression with estrogen (ER) and progesterone (PgR) receptor status, p53 and Ki-67 immunoreactivity, as well as with other clinicopathological parameters in breast cancer patients. HER2/neu, ER/PgR status, p53 and Ki-67 expression was determined in 169 postoperative stage I-III (UICC, 1997) breast cancer patients using the standardized DAKO HercepsTest¨ and by the immunoperoxidase technique, respectively. The results were evaluated by performing the standardized scoring system. The values of HER2/neu expression were correlated to ER/PgR status, p53 and Ki-67 immunoreactivity and to clinicopathological parameters (tumor size, histopathologic grade, nuclear grade, tumor type, and lymph node status and patients’ age). The statistical significance was determined with c2 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, p53 or Ki-67 immunoreactivity, neither with any other clinicopathological parameter. ER is associated with PgR, tumor size, tumor type and lymph node status (p<0.01); PgR with histopathologic grade, tumor type and lymph node status (p<0.01) and Ki-67 with p53 immunoreactivity, tumor size and patients’ age (p<0.01). The results of the current study 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 the clinical outcome.
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Benign and malignant pigmented lesions of the female genital tract (FGT). Report of 15 cases.
(Springer, 2001-09)
Kubelka, Katerina
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Yashar, Genghis
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Prodanova, Irina
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Ivkovski, Ljube
Introduction: Benign and malignant pigmented lesions (PL) of the FGT are uncommon, predominantly affecting the vulva. Methods: We report the clinical and pathological features of the 15 PL of the FGT retrieved in a 12-year, retrospective analysis at our Department. Patient records and archival pathology specimens of 7 benign and 8 malignant PL of the FGT, were reviewed. Results: The mean age of all patients was 47 (range, 28-67). Three patients had vulvar nevi (2 intradermal and 1 dysplastic), while blue nevi ranging 2-10 mm in diameter were accidentally discovered in the endocervix of the hysterectomy specimens in four other patients. Vulvar primary malignant melanomas (PMMs) were uncommon (4 cases), comprising 2.5% of female PMMs and 4.3% of all vulvar malignancies diagnosed between 1989 and 2000. Contrary to other studies, all vulvar PMM in our series were of nodular type, ranging 3-13 mm in depth according to Breslow and III-IV level according to Clark. Within the same period, two patients with malignant PL of the uterine cervix were detected, accounting for 0.13% of all females with malignant cervical neoplasms. One of them had a PMM diagnosed in advanced clinical stage (FIGO III), and the other patient had an unusual pigmented squamous cell carcinoma in liB postoperative stage. There were also 2 cases of delayed unilateral ovarian metastases of cutaneous PMM. The diagnosis in all cases of non-vulvar pigmented lesions was confirmed by immunohistochemistry. Conclusions: Although uncommon, PL especially those affecting rare localizations must be considered as diagnostic possibility in FGT.
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Myoepithelial carcinoma of the breast arising in adenomyoepithelioma. A case report.
(Springer, 2001-09)
Yashar, Genghis
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Ivkovski, Ljube
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Kubelka, Katerina
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Zografski, George
Introduction: Adenomyoepithelioma (AME), and especially myoepithelial carcinoma (MC), the malignant variant of this tumor, is a rare breast neoplasm. This report comprises the pathological features of a breast MC arising in AME with an aggressive clinical course. Case report: A 48-year old woman with a palpable mass in the right breast was admitted in November 1998. A month later following FNAB, surgical excision was performed. During the follow-up period of 17 months, until the patient's death, two local recurrences developed. Despite the aggressive chemotherapy, administrated after the first recurrence, subsequently bone, pulmonary and brain metastases appeared. Results: The primary tumor was an ovoid, white-grey, encapsulated mass measuring 4x3,5x1,5 cm. Microscopically, this biphasic tumor was composed of rare tubules surrounded by interlacing bundles of spindle cells exhibiting mild atypia. It was initially classified as a benign phyllodes tumor. The immunohistochemical analyses performed after the second recurrence proved the myoepithelial origin of the neoplasm (S-100, cytokeratin and alpha-SMA positive cells), with a high mitotic index (11 MF/10 HPF), and an immunophenotype indicating aggressive biological potential (steroid receptor negative, 50% Ki-67 and 30% p53 positive cells). Therefore, it was reclassified as MC arising in spindle cell type of AME. Conclusion: The histopathological diagnosis of AME could be very difficult, especially when a distinction from other spindle cell breast neoplasms must be done. Immunohistochemistry is essential to confirm the diagnosis, having in mind the reported pathological characteristics and the immunohistochemical profile of recurrent and malignant tumors of this type.
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Histological and immunohistochemichemical study of malignant lymphomas in Macedonia - Study of 222 cases
(Macedonian Association of Pathology, 2013)
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Ivkovski, Ljube
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